Le module SPF a pour mission d’héberger et reproduire les lignées transgéniques et de garantir le statut sanitaire « Specific Pathogen Free ».
Ce niveau sanitaire est défini par rapport à une liste de référence d’organismes pathogènes viraux, bactériens ou parasitaires à exclure des élevages. Ainsi, l’absence de ces pathogènes assure le bien-être des animaux, la qualité de la reproduction et la fiabilité des résultats expérimentaux. Le maintien de ce statut préserve les élevages de catastrophes sanitaires pouvant avoir des impacts scientifiques et financiers importants. Un autre avantage du statut sanitaire SPF est la facilitation des échanges de lignées transgéniques pour des collaborations scientifiques nationales et internationales. En effet, la délivrance de certificats statuts sanitaires SPF accélère les démarches administratives et les acceptations d’échange auprès des services vétérinaires, douaniers et responsables d’animaleries.
La plateforme animalière SPF a également pour mission de cryoconserver les lignées de souris, transgéniques principalement.
Prestations
Hébergement et gestion de lignée
Le module SPF vous propose de conserver vos lignées sous forme respirante au statut sanitaire SPF. Le propriétaire de la lignée gère ces colonies par l’intermédiaire du logiciel de gestion Mayakind. Le travail de suivi du bien-être animal et de la gestion des lignées (identification, biopsie, sevrage) est assuré par l’équipe de 5 zootechniciens. Annuellement 800 croisements sont lancés, 12 000 souriceaux sont ainsi générés. Près de 2500 souris sont sorties annuellement du module SPF pour expérimentation dans les différents centres de recherche de Lyon.
Transfert aseptique d’embryon
Pour que les lignées n’ayant pas le statut SPF puissent accéder à la plateforme SPF, il faut « décontaminer » ces lignées par une technique d’embryologie appelée « transfert aseptique d’embryons». Nous demandons de nous fournir 3-5 mâles qui seront hébergés au module 2 d’ALECS qui n’a aucun contact avec le module SPF. Seules les femelles superovulées seront mises en contact pendant une nuit. La suite de la technique consiste à nettoyer les embryons fécondés par bains successifs, puis de les réimplanter par microchirurgie au niveau de l’ovaire de mères porteuses dans des conditions aseptiques au niveau des expérimentales du SPF. Un contrôle sanitaire est réalisé afin de confirmer l’élimination des pathogènes sur les souriceaux obtenus.
Cryopréservation des lignées
La cryopréservation est l’ensemble des techniques qui consistent à la congélation des gamètes des lignées de souris transgéniques dans l’azote et à la reviviscence des souris. Ces savoir-faire permettent la « sauvegarde » de lignées. Elles sont ainsi protégées de la dérive génétique et peuvent être revivifiées à tout moment en cas de problèmes sanitaires ou de problème de stérilité. De plus, avec le renforcement de la réglementation du transport des animaux et des difficultés qui en découlent, l’échange de souches via du matériel congelé est une solution de plus en plus employée. Enfin, la cryoconservation permet de réduire le nombre de lignées vivantes, ce qui est en parfait accord avec la règle de réduction des animaux.
Cryopréservation de sperme
Nous proposons la cryopréservation de sperme via le Jax Sperm Cryo Kit. Pour cela, il faut nous fournir deux mâles de 10-16 semaines le jour des prélèvements. Nous nous occupons de récupérer les spermatozoïdes dans les milieux appropriés du kit, de réaliser 20 paillettes et de les congeler selon le protocole. Les paillettes sont ensuite envoyées via un dry-shipper sur le site de Janvier Labs. Un contrôle qualité (Fécondation In Vitro) est alors réalisé par la société Janvier Labs sur une des paillettes envoyées sur le fonds génétique que vous préciserez. Le pourcentage de passage à deux cellules valide la qualité des paillettes. Le stock se fait par la société Janvier Labs (environ 100 €/an/lignée à votre charge) sur deux sites sécurisés. Vous pouvez également choisir de stocker vos paillettes dans vos propres bacs à azote.
Fécondation In Vitro
La reviviscence de lignée à partir de paillettes congelées est une prestation récemment développée dans notre service. Merci de nous consulter pour les conditions de réalisation.
Présentation du bâtiment et statut sanitaire
La plateforme a été conçue et fonctionne pour maintenir le statut SPF :
- filtration de l’air entrant par la centrale de traitement d’air ;
- zone protégée en surpression instaurant un gradient de pression décroissant des zones les plus propres à la laverie ;
- stérilisation de tous les produits entrants (eau, aliment, litière, cage…) par autoclave double entrée, sas à désinfection gazeuse ou filtration ;
- procédures strictes concernant le circuit des déchets et le ménage ;
- procédures particulières concernant le personnel entrant en zone protégée (douche à chaque entrée, vêtements stériles changés quotidiennement, port d’un masque et d’une charlotte, changement fréquent des gants) ;
- achat d’animaux au statut sanitaire SPF, livrés par les fournisseurs agréés (Charles River, Harlan…).
Un contrôle sanitaire (bactériologie, virologie, parasitologie) des animaux sentinelles est réalisé tous les trimestres afin de vérifier le maintien du statut SPF de la plateforme.
Contact
Bibliographie
Voici les derniers articles déclarés pour la plateforme ALECS SPF :
6024536
LUQ7ZPMM
1
apa
10
default
95
https://sfrsantelyonest.univ-lyon1.fr/wp-content/plugins/zotpress/
%7B%22status%22%3A%22success%22%2C%22updateneeded%22%3Afalse%2C%22instance%22%3Afalse%2C%22meta%22%3A%7B%22request_last%22%3A0%2C%22request_next%22%3A0%2C%22used_cache%22%3Atrue%7D%2C%22data%22%3A%5B%7B%22key%22%3A%22WFUBZ2BS%22%2C%22library%22%3A%7B%22id%22%3A6024536%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Monteillet%20et%20al.%22%2C%22parsedDate%22%3A%222022-03-21%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%26lt%3Bdiv%20class%3D%26quot%3Bcsl-bib-body%26quot%3B%20style%3D%26quot%3Bline-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%26quot%3B%26gt%3B%5Cn%20%20%26lt%3Bdiv%20class%3D%26quot%3Bcsl-entry%26quot%3B%26gt%3BMonteillet%2C%20L.%2C%20Labrune%2C%20P.%2C%20Hochuli%2C%20M.%2C%20Do%20Cao%2C%20J.%2C%20Tortereau%2C%20A.%2C%20Miliano%2C%20A.%20C.%2C%20Ardon-Zitoun%2C%20C.%2C%20Duchampt%2C%20A.%2C%20Silva%2C%20M.%2C%20Verzieux%2C%20V.%2C%20Mithieux%2C%20G.%2C%20%26amp%3B%20Rajas%2C%20F.%20%282022%29.%20Cellular%20and%20metabolic%20effects%20of%20renin-angiotensin%20system%20blockade%20on%20glycogen%20storage%20disease%20type%20I%20nephropathy.%20%26lt%3Bi%26gt%3BHuman%20Molecular%20Genetics%26lt%3B%5C%2Fi%26gt%3B%2C%20%26lt%3Bi%26gt%3B31%26lt%3B%5C%2Fi%26gt%3B%286%29%2C%20914%26%23×2013%3B928.%20%26lt%3Ba%20class%3D%26%23039%3Bzp-DOIURL%26%23039%3B%20href%3D%26%23039%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1093%5C%2Fhmg%5C%2Fddab297%26%23039%3B%26gt%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1093%5C%2Fhmg%5C%2Fddab297%26lt%3B%5C%2Fa%26gt%3B%26lt%3B%5C%2Fdiv%26gt%3B%5Cn%26lt%3B%5C%2Fdiv%26gt%3B%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Cellular%20and%20metabolic%20effects%20of%20renin-angiotensin%20system%20blockade%20on%20glycogen%20storage%20disease%20type%20I%20nephropathy%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Laure%22%2C%22lastName%22%3A%22Monteillet%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Philippe%22%2C%22lastName%22%3A%22Labrune%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Michel%22%2C%22lastName%22%3A%22Hochuli%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jeremy%22%2C%22lastName%22%3A%22Do%20Cao%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Antonin%22%2C%22lastName%22%3A%22Tortereau%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Alexane%20Cannella%22%2C%22lastName%22%3A%22Miliano%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Carine%22%2C%22lastName%22%3A%22Ardon-Zitoun%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Adeline%22%2C%22lastName%22%3A%22Duchampt%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Marine%22%2C%22lastName%22%3A%22Silva%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Vincent%22%2C%22lastName%22%3A%22Verzieux%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Gilles%22%2C%22lastName%22%3A%22Mithieux%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Fabienne%22%2C%22lastName%22%3A%22Rajas%22%7D%5D%2C%22abstractNote%22%3A%22Abstract%5Cn%20%20%20%20%20%20%20%20%20%20%20%20Glycogen%20Storage%20Disease%20Type%20I%20%28GSDI%29%20is%20an%20inherited%20disease%20caused%20by%20glucose-6%20phosphatase%20%28G6Pase%29%20deficiency%2C%20leading%20to%20a%20loss%20of%20endogenous%20glucose%20production%20and%20severe%20hypoglycemia.%20Moreover%2C%20most%20GSDI%20patients%20develop%20a%20chronic%20kidney%20disease%20%28CKD%29%20due%20to%20lipid%20accumulation%20in%20the%20kidney.%20Similar%20to%20diabetic%20CKD%2C%20activation%20of%20renin-angiotensin%20system%20%28RAS%29%20promotes%20renal%20fibrosis%20in%20GSDI.%20Here%2C%20we%20investigated%20the%20physiological%20and%20molecular%20effects%20of%20RAS%20blockers%20in%20GSDI%20patients%20and%20mice.%20A%20retrospective%20analysis%20of%20renal%20function%20was%20performed%20in%2021%20GSDI%20patients%20treated%20with%20RAS%20blockers.%20Cellular%20and%20metabolic%20impacts%20of%20RAS%20blockade%20were%20analyzed%20in%20K.G6pc%5Cu2212%5C%2F%5Cu2212%20mice%20characterized%20by%20G6pc1%20deletion%20in%20kidneys.%20GSDI%20patients%20started%20RAS%20blocker%20treatment%20at%20a%20median%20age%20of%2021%5Cu00a0years%20and%20long-term%20treatment%20reduced%20the%20progression%20of%20CKD%20in%20about%2050%25%20of%20patients.%20However%2C%20CKD%20progressed%20to%20kidney%20failure%20in%2020%25%20of%20treated%20patients%2C%20requiring%20renal%20transplantation.%20In%20K.G6pc%5Cu2212%5C%2F%5Cu2212%20mice%2C%20CKD%20was%20associated%20with%20an%20impairment%20of%20autophagy%20and%20ER%20stress.%20RAS%20blockade%20resulted%20in%20a%20rescue%20of%20autophagy%20and%20decreased%20ER%20stress%2C%20concomitantly%20with%20decreased%20fibrosis%20and%20improved%20renal%20function%2C%20but%20without%20impact%20on%20glycogen%20and%20lipid%20contents.%20In%20conclusion%2C%20these%20data%20confirm%20the%20partial%20beneficial%20effect%20of%20RAS%20blockers%20in%20the%20prevention%20of%20CKD%20in%20GSDI.%20Mechanistically%2C%20we%20show%20that%20these%20effects%20are%20linked%20to%20a%20reduction%20of%20cell%20stress%2C%20without%20affecting%20metabolism.%22%2C%22date%22%3A%222022-03-21%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1093%5C%2Fhmg%5C%2Fddab297%22%2C%22ISSN%22%3A%220964-6906%2C%201460-2083%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Facademic.oup.com%5C%2Fhmg%5C%2Farticle%5C%2F31%5C%2F6%5C%2F914%5C%2F6382535%22%2C%22collections%22%3A%5B%22K5DKASFS%22%2C%22LUQ7ZPMM%22%2C%22FKFCWCTY%22%5D%2C%22dateModified%22%3A%222025-06-13T09%3A42%3A04Z%22%7D%7D%2C%7B%22key%22%3A%22YQ5XL8UN%22%2C%22library%22%3A%7B%22id%22%3A6024536%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Gautier-Stein%20et%20al.%22%2C%22parsedDate%22%3A%222023%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%26lt%3Bdiv%20class%3D%26quot%3Bcsl-bib-body%26quot%3B%20style%3D%26quot%3Bline-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%26quot%3B%26gt%3B%5Cn%20%20%26lt%3Bdiv%20class%3D%26quot%3Bcsl-entry%26quot%3B%26gt%3BGautier-Stein%2C%20A.%2C%20Chilloux%2C%20J.%2C%20Soty%2C%20M.%2C%20Thorens%2C%20B.%2C%20Place%2C%20C.%2C%20Zitoun%2C%20C.%2C%20Duchampt%2C%20A.%2C%20Da%20Costa%2C%20L.%2C%20Rajas%2C%20F.%2C%20Lamaze%2C%20C.%2C%20%26amp%3B%20Mithieux%2C%20G.%20%282023%29.%20A%20caveolin-1%20dependent%20glucose-6-phosphatase%20trafficking%20contributes%20to%20hepatic%20glucose%20production.%20%26lt%3Bi%26gt%3BMolecular%20Metabolism%26lt%3B%5C%2Fi%26gt%3B%2C%20%26lt%3Bi%26gt%3B70%26lt%3B%5C%2Fi%26gt%3B%2C%20101700.%20%26lt%3Ba%20class%3D%26%23039%3Bzp-DOIURL%26%23039%3B%20href%3D%26%23039%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1016%5C%2Fj.molmet.2023.101700%26%23039%3B%26gt%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1016%5C%2Fj.molmet.2023.101700%26lt%3B%5C%2Fa%26gt%3B%26lt%3B%5C%2Fdiv%26gt%3B%5Cn%26lt%3B%5C%2Fdiv%26gt%3B%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22A%20caveolin-1%20dependent%20glucose-6-phosphatase%20trafficking%20contributes%20to%20hepatic%20glucose%20production%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Amandine%22%2C%22lastName%22%3A%22Gautier-Stein%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Julien%22%2C%22lastName%22%3A%22Chilloux%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Maud%22%2C%22lastName%22%3A%22Soty%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Bernard%22%2C%22lastName%22%3A%22Thorens%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Christophe%22%2C%22lastName%22%3A%22Place%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Carine%22%2C%22lastName%22%3A%22Zitoun%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Adeline%22%2C%22lastName%22%3A%22Duchampt%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Lorine%22%2C%22lastName%22%3A%22Da%20Costa%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Fabienne%22%2C%22lastName%22%3A%22Rajas%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Christophe%22%2C%22lastName%22%3A%22Lamaze%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Gilles%22%2C%22lastName%22%3A%22Mithieux%22%7D%5D%2C%22abstractNote%22%3A%22%22%2C%22date%22%3A%2204%5C%2F2023%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1016%5C%2Fj.molmet.2023.101700%22%2C%22ISSN%22%3A%2222128778%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Flinkinghub.elsevier.com%5C%2Fretrieve%5C%2Fpii%5C%2FS2212877823000340%22%2C%22collections%22%3A%5B%22K5DKASFS%22%2C%22LUQ7ZPMM%22%2C%22FKFCWCTY%22%5D%2C%22dateModified%22%3A%222025-06-13T09%3A22%3A15Z%22%7D%7D%2C%7B%22key%22%3A%222S5VS4LP%22%2C%22library%22%3A%7B%22id%22%3A6024536%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Estrada-Meza%20et%20al.%22%2C%22parsedDate%22%3A%222021-07-01%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%26lt%3Bdiv%20class%3D%26quot%3Bcsl-bib-body%26quot%3B%20style%3D%26quot%3Bline-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%26quot%3B%26gt%3B%5Cn%20%20%26lt%3Bdiv%20class%3D%26quot%3Bcsl-entry%26quot%3B%26gt%3BEstrada-Meza%2C%20J.%2C%20Videlo%2C%20J.%2C%20Bron%2C%20C.%2C%20Saint-B%26%23xE9%3Bat%2C%20C.%2C%20Silva%2C%20M.%2C%20Duboeuf%2C%20F.%2C%20Peyruchaud%2C%20O.%2C%20Rajas%2C%20F.%2C%20Mithieux%2C%20G.%2C%20%26amp%3B%20Gautier-Stein%2C%20A.%20%282021%29.%20Tamoxifen%20Treatment%20in%20the%20Neonatal%20Period%20Affects%20Glucose%20Homeostasis%20in%20Adult%20Mice%20in%20a%20Sex-Dependent%20Manner.%20%26lt%3Bi%26gt%3BEndocrinology%26lt%3B%5C%2Fi%26gt%3B%2C%20%26lt%3Bi%26gt%3B162%26lt%3B%5C%2Fi%26gt%3B%287%29%2C%20bqab098.%20%26lt%3Ba%20class%3D%26%23039%3Bzp-DOIURL%26%23039%3B%20href%3D%26%23039%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1210%5C%2Fendocr%5C%2Fbqab098%26%23039%3B%26gt%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1210%5C%2Fendocr%5C%2Fbqab098%26lt%3B%5C%2Fa%26gt%3B%26lt%3B%5C%2Fdiv%26gt%3B%5Cn%26lt%3B%5C%2Fdiv%26gt%3B%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Tamoxifen%20Treatment%20in%20the%20Neonatal%20Period%20Affects%20Glucose%20Homeostasis%20in%20Adult%20Mice%20in%20a%20Sex-Dependent%20Manner%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Judith%22%2C%22lastName%22%3A%22Estrada-Meza%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jasmine%22%2C%22lastName%22%3A%22Videlo%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Clara%22%2C%22lastName%22%3A%22Bron%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22C%5Cu00e9cile%22%2C%22lastName%22%3A%22Saint-B%5Cu00e9at%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Marine%22%2C%22lastName%22%3A%22Silva%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Fran%5Cu00e7ois%22%2C%22lastName%22%3A%22Duboeuf%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Olivier%22%2C%22lastName%22%3A%22Peyruchaud%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Fabienne%22%2C%22lastName%22%3A%22Rajas%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Gilles%22%2C%22lastName%22%3A%22Mithieux%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Amandine%22%2C%22lastName%22%3A%22Gautier-Stein%22%7D%5D%2C%22abstractNote%22%3A%22Abstract%5Cn%20%20%20%20%20%20%20%20%20%20%20%20Tamoxifen%20is%20a%20selective%20estrogen%20receptor%20modulator%20used%20to%20activate%20the%20CREERT2%20recombinase%2C%20allowing%20tissue-specific%20and%20temporal%20control%20of%20the%20somatic%20mutagenesis%20to%20generate%20transgenic%20mice.%20Studies%20integrating%20development%20and%20metabolism%20require%20a%20genetic%20modification%20induced%20by%20a%20neonatal%20tamoxifen%20administration.%20Here%2C%20we%20investigate%20the%20effects%20of%20a%20neonatal%20tamoxifen%20administration%20on%20energy%20homeostasis%20in%20adult%20male%20and%20female%20C57BL%5C%2F6J%20mice.%20C57BL%5C%2F6J%20male%20and%20female%20mouse%20pups%20received%20a%20single%20injection%20of%20tamoxifen%201%20day%20after%20birth%20%28NTT%29%20and%20were%20fed%20a%20high-fat%5C%2Fhigh-sucrose%20diet%20at%206%20weeks%20of%20age.%20We%20measured%20weight%2C%20body%20composition%2C%20glucose%20and%20insulin%20tolerance%2C%20basal%20metabolism%2C%20and%20tibia%20length%20and%20weight%20in%20adult%20mice.%20The%20neonatal%20tamoxifen%20administration%20exerted%20long-term%2C%20sex-dependent%20effects%20on%20energy%20homeostasis.%20NTT%20female%20mice%20became%20overweight%20and%20developed%20impaired%20glucose%20control%20in%20comparison%20to%20vehicle-treated%20littermates.%20NTT%20females%20exhibited%2060%25%20increased%20fat%20mass%2C%20increased%20food%20intake%2C%20decreased%20physical%20activity%20and%20energy%20expenditure%2C%20impaired%20glucose%20and%20insulin%20tolerance%2C%20and%20fasting%20hyperglycemia%20and%20hyperinsulinemia.%20In%20contrast%2C%20NTT%20male%20mice%20exhibited%20a%20modest%20amelioration%20of%20glucose%20and%20insulin%20tolerance%20and%20long-term%20decreased%20lean%20mass%20linked%20to%20decreased%20bone%20weight.%20These%20results%20suggest%20that%20the%20neonatal%20tamoxifen%20administration%20exerted%20a%20marked%20and%20sex-dependent%20influence%20on%20adult%20energy%20homeostasis%20and%20bone%20weight%20and%20must%20therefore%20be%20used%20with%20caution%20for%20the%20development%20of%20transgenic%20mouse%20models%20regarding%20studies%20on%20energy%20homeostasis%20and%20bone%20biology.%22%2C%22date%22%3A%222021-07-01%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1210%5C%2Fendocr%5C%2Fbqab098%22%2C%22ISSN%22%3A%220013-7227%2C%201945-7170%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Facademic.oup.com%5C%2Fendo%5C%2Farticle%5C%2Fdoi%5C%2F10.1210%5C%2Fendocr%5C%2Fbqab098%5C%2F6277101%22%2C%22collections%22%3A%5B%22K5DKASFS%22%2C%22LUQ7ZPMM%22%2C%22CUU5LTIV%22%2C%22FKFCWCTY%22%5D%2C%22dateModified%22%3A%222025-06-13T09%3A18%3A53Z%22%7D%7D%2C%7B%22key%22%3A%22GTQ27FXF%22%2C%22library%22%3A%7B%22id%22%3A6024536%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Vily%5Cu2010Petit%20et%20al.%22%2C%22parsedDate%22%3A%222024%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%26lt%3Bdiv%20class%3D%26quot%3Bcsl-bib-body%26quot%3B%20style%3D%26quot%3Bline-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%26quot%3B%26gt%3B%5Cn%20%20%26lt%3Bdiv%20class%3D%26quot%3Bcsl-entry%26quot%3B%26gt%3BVily%26%23×2010%3BPetit%2C%20J.%2C%20Soty%26%23×2010%3BRoca%2C%20M.%2C%20Silva%2C%20M.%2C%20Micoud%2C%20M.%2C%20Evrard%2C%20F.%2C%20Bron%2C%20C.%2C%20Raffin%2C%20M.%2C%20Beiroa%2C%20D.%2C%20Nogueiras%2C%20R.%2C%20Roussel%2C%20D.%2C%20Gautier%26%23×2010%3BStein%2C%20A.%2C%20Rajas%2C%20F.%2C%20Cota%2C%20D.%2C%20%26amp%3B%20Mithieux%2C%20G.%20%282024%29.%20Antiobesity%20effects%20of%20intestinal%20gluconeogenesis%20are%20mediated%20by%20the%20brown%20adipose%20tissue%20sympathetic%20nervous%20system.%20%26lt%3Bi%26gt%3BObesity%26lt%3B%5C%2Fi%26gt%3B%2C%20%26lt%3Bi%26gt%3B32%26lt%3B%5C%2Fi%26gt%3B%284%29%2C%20710%26%23×2013%3B722.%20%26lt%3Ba%20class%3D%26%23039%3Bzp-DOIURL%26%23039%3B%20href%3D%26%23039%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1002%5C%2Foby.23985%26%23039%3B%26gt%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1002%5C%2Foby.23985%26lt%3B%5C%2Fa%26gt%3B%26lt%3B%5C%2Fdiv%26gt%3B%5Cn%26lt%3B%5C%2Fdiv%26gt%3B%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Antiobesity%20effects%20of%20intestinal%20gluconeogenesis%20are%20mediated%20by%20the%20brown%20adipose%20tissue%20sympathetic%20nervous%20system%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Justine%22%2C%22lastName%22%3A%22Vily%5Cu2010Petit%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Maud%22%2C%22lastName%22%3A%22Soty%5Cu2010Roca%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Marine%22%2C%22lastName%22%3A%22Silva%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Manon%22%2C%22lastName%22%3A%22Micoud%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22F%5Cu00e9licie%22%2C%22lastName%22%3A%22Evrard%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Clara%22%2C%22lastName%22%3A%22Bron%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Margaux%22%2C%22lastName%22%3A%22Raffin%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Daniel%22%2C%22lastName%22%3A%22Beiroa%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Rub%5Cu00e9n%22%2C%22lastName%22%3A%22Nogueiras%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Damien%22%2C%22lastName%22%3A%22Roussel%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Amandine%22%2C%22lastName%22%3A%22Gautier%5Cu2010Stein%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Fabienne%22%2C%22lastName%22%3A%22Rajas%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Daniela%22%2C%22lastName%22%3A%22Cota%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Gilles%22%2C%22lastName%22%3A%22Mithieux%22%7D%5D%2C%22abstractNote%22%3A%22Abstract%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20Objective%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20Intestinal%20gluconeogenesis%20%28IGN%29%2C%20via%20the%20initiation%20of%20a%20gut%5Cu2010brain%20nervous%20circuit%2C%20accounts%20for%20the%20metabolic%20benefits%20linked%20to%20dietary%20proteins%20or%20fermentable%20fiber%20in%20rodents%20and%20has%20been%20positively%20correlated%20with%20the%20rapid%20amelioration%20of%20body%20weight%20after%20gastric%20bypass%20surgery%20in%20humans%20with%20obesity.%20In%20particular%2C%20the%20activation%20of%20IGN%20moderates%20the%20development%20of%20hepatic%20steatosis%20accompanying%20obesity.%20In%20this%20study%2C%20we%20investigated%20the%20specific%20effects%20of%20IGN%20on%20adipose%20tissue%20metabolism%2C%20independent%20of%20its%20induction%20by%20nutritional%20manipulation.%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20Methods%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20We%20used%20two%20transgenic%20mouse%20models%20of%20suppression%20or%20overexpression%20of%20G6pc1%2C%20the%20catalytic%20subunit%20of%20glucose%5Cu20106%20phosphatase%2C%20which%20is%20the%20key%20enzyme%20of%20endogenous%20glucose%20production%20specifically%20in%20the%20intestine.%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20Results%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20Under%20a%20hypercaloric%20diet%2C%20mice%20overexpressing%20IGN%20showed%20lower%20adiposity%20and%20higher%20thermogenic%20capacities%20than%20wild%5Cu2010type%20mice%2C%20featuring%20marked%20browning%20of%20white%20adipose%20tissue%20%28WAT%29%20and%20prevention%20of%20the%20whitening%20of%20brown%20adipose%20tissue%20%28BAT%29.%20Sympathetic%20denervation%20restricted%20to%20BAT%20caused%20the%20loss%20of%20the%20antiobesity%20effects%20associated%20with%20IGN.%20Conversely%2C%20IGN%5Cu2010deficient%20mice%20exhibited%20an%20increase%20in%20adiposity%20under%20a%20standard%20diet%2C%20which%20was%20associated%20with%20decreased%20expression%20of%20markers%20of%20thermogenesis%20in%20both%20BAT%20and%20WAT.%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20Conclusions%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20IGN%20is%20sufficient%20to%20activate%20the%20sympathetic%20nervous%20system%20and%20prevent%20the%20expansion%20and%20the%20metabolic%20alterations%20of%20BAT%20and%20WAT%20metabolism%20under%20a%20high%5Cu2010calorie%20diet%2C%20thereby%20preventing%20the%20development%20of%20obesity.%20These%20data%20increase%20knowledge%20of%20the%20mechanisms%20of%20weight%20reduction%20in%20gastric%20bypass%20surgery%20and%20pave%20the%20way%20for%20new%20approaches%20to%20prevent%20or%20cure%20obesity.%22%2C%22date%22%3A%2204%5C%2F2024%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1002%5C%2Foby.23985%22%2C%22ISSN%22%3A%221930-7381%2C%201930-739X%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fonlinelibrary.wiley.com%5C%2Fdoi%5C%2F10.1002%5C%2Foby.23985%22%2C%22collections%22%3A%5B%22K5DKASFS%22%2C%22LUQ7ZPMM%22%2C%22CUU5LTIV%22%2C%22FKFCWCTY%22%5D%2C%22dateModified%22%3A%222025-06-13T09%3A10%3A48Z%22%7D%7D%2C%7B%22key%22%3A%22A7AXUPCZ%22%2C%22library%22%3A%7B%22id%22%3A6024536%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Rajas%20et%20al.%22%2C%22parsedDate%22%3A%222021%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%26lt%3Bdiv%20class%3D%26quot%3Bcsl-bib-body%26quot%3B%20style%3D%26quot%3Bline-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%26quot%3B%26gt%3B%5Cn%20%20%26lt%3Bdiv%20class%3D%26quot%3Bcsl-entry%26quot%3B%26gt%3BRajas%2C%20F.%2C%20Dentin%2C%20R.%2C%20Cannella%20Miliano%2C%20A.%2C%20Silva%2C%20M.%2C%20Raffin%2C%20M.%2C%20Levavasseur%2C%20F.%2C%20Gautier-Stein%2C%20A.%2C%20Postic%2C%20C.%2C%20%26amp%3B%20Mithieux%2C%20G.%20%282021%29.%20The%20absence%20of%20hepatic%20glucose-6%20phosphatase%5C%2FChREBP%20couple%20is%20incompatible%20with%20survival%20in%20mice.%20%26lt%3Bi%26gt%3BMolecular%20Metabolism%26lt%3B%5C%2Fi%26gt%3B%2C%20%26lt%3Bi%26gt%3B43%26lt%3B%5C%2Fi%26gt%3B%2C%20101108.%20%26lt%3Ba%20class%3D%26%23039%3Bzp-DOIURL%26%23039%3B%20href%3D%26%23039%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1016%5C%2Fj.molmet.2020.101108%26%23039%3B%26gt%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1016%5C%2Fj.molmet.2020.101108%26lt%3B%5C%2Fa%26gt%3B%26lt%3B%5C%2Fdiv%26gt%3B%5Cn%26lt%3B%5C%2Fdiv%26gt%3B%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22The%20absence%20of%20hepatic%20glucose-6%20phosphatase%5C%2FChREBP%20couple%20is%20incompatible%20with%20survival%20in%20mice%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Fabienne%22%2C%22lastName%22%3A%22Rajas%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Renaud%22%2C%22lastName%22%3A%22Dentin%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Alexane%22%2C%22lastName%22%3A%22Cannella%20Miliano%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Marine%22%2C%22lastName%22%3A%22Silva%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Margaux%22%2C%22lastName%22%3A%22Raffin%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Fran%5Cu00e7oise%22%2C%22lastName%22%3A%22Levavasseur%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Amandine%22%2C%22lastName%22%3A%22Gautier-Stein%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Catherine%22%2C%22lastName%22%3A%22Postic%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Gilles%22%2C%22lastName%22%3A%22Mithieux%22%7D%5D%2C%22abstractNote%22%3A%22%22%2C%22date%22%3A%2201%5C%2F2021%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1016%5C%2Fj.molmet.2020.101108%22%2C%22ISSN%22%3A%2222128778%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Flinkinghub.elsevier.com%5C%2Fretrieve%5C%2Fpii%5C%2FS2212877820301824%22%2C%22collections%22%3A%5B%22K5DKASFS%22%2C%22LUQ7ZPMM%22%2C%22FKFCWCTY%22%5D%2C%22dateModified%22%3A%222025-06-13T09%3A02%3A31Z%22%7D%7D%2C%7B%22key%22%3A%22FHKYTHC5%22%2C%22library%22%3A%7B%22id%22%3A6024536%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Sinet%20et%20al.%22%2C%22parsedDate%22%3A%222021%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%26lt%3Bdiv%20class%3D%26quot%3Bcsl-bib-body%26quot%3B%20style%3D%26quot%3Bline-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%26quot%3B%26gt%3B%5Cn%20%20%26lt%3Bdiv%20class%3D%26quot%3Bcsl-entry%26quot%3B%26gt%3BSinet%2C%20F.%2C%20Soty%2C%20M.%2C%20Zemdegs%2C%20J.%2C%20Guiard%2C%20B.%2C%20Estrada%2C%20J.%2C%20Malleret%2C%20G.%2C%20Silva%2C%20M.%2C%20Mithieux%2C%20G.%2C%20%26amp%3B%20Gautier-Stein%2C%20A.%20%282021%29.%20Dietary%20Fibers%20and%20Proteins%20Modulate%20Behavior%20via%20the%20Activation%20of%20Intestinal%20Gluconeogenesis.%20%26lt%3Bi%26gt%3BNeuroendocrinology%26lt%3B%5C%2Fi%26gt%3B%2C%20%26lt%3Bi%26gt%3B111%26lt%3B%5C%2Fi%26gt%3B%2812%29%2C%201249%26%23×2013%3B1265.%20%26lt%3Ba%20class%3D%26%23039%3Bzp-DOIURL%26%23039%3B%20href%3D%26%23039%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1159%5C%2F000514289%26%23039%3B%26gt%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1159%5C%2F000514289%26lt%3B%5C%2Fa%26gt%3B%26lt%3B%5C%2Fdiv%26gt%3B%5Cn%26lt%3B%5C%2Fdiv%26gt%3B%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Dietary%20Fibers%20and%20Proteins%20Modulate%20Behavior%20via%20the%20Activation%20of%20Intestinal%20Gluconeogenesis%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Flore%22%2C%22lastName%22%3A%22Sinet%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Maud%22%2C%22lastName%22%3A%22Soty%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Juliane%22%2C%22lastName%22%3A%22Zemdegs%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Bruno%22%2C%22lastName%22%3A%22Guiard%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Judith%22%2C%22lastName%22%3A%22Estrada%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ga%5Cu00ebl%22%2C%22lastName%22%3A%22Malleret%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Marine%22%2C%22lastName%22%3A%22Silva%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Gilles%22%2C%22lastName%22%3A%22Mithieux%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Amandine%22%2C%22lastName%22%3A%22Gautier-Stein%22%7D%5D%2C%22abstractNote%22%3A%22%26lt%3Bb%26gt%3B%26lt%3Bi%26gt%3BIntroduction%3A%26lt%3B%5C%2Fi%26gt%3B%26lt%3B%5C%2Fb%26gt%3B%20Several%20studies%20have%20suggested%20that%20diet%2C%20especially%20the%20one%20enriched%20in%20microbiota-fermented%20fibers%20or%20fat%2C%20regulates%20behavior.%20The%20underlying%20mechanisms%20are%20currently%20unknown.%20We%20previously%20reported%20that%20certain%20macronutrients%20%28fermentable%20fiber%20and%20protein%29%20regulate%20energy%20homeostasis%20via%20the%20activation%20of%20intestinal%20gluconeogenesis%20%28IGN%29%2C%20which%20generates%20a%20neural%20signal%20to%20the%20brain.%20We%20hypothesized%20that%20these%20nutriments%20might%20control%20behavior%20using%20the%20same%20gut-brain%20circuit.%20%26lt%3Bb%26gt%3B%26lt%3Bi%26gt%3BMethods%3A%26lt%3B%5C%2Fi%26gt%3B%26lt%3B%5C%2Fb%26gt%3B%20Wild-type%20and%20IGN-deficient%20mice%20were%20fed%20chow%20or%20diets%20enriched%20in%20protein%20or%20fiber.%20Changes%20in%20their%20behavior%20were%20assessed%20using%20suited%20tests.%20Hippocampal%20neurogenesis%2C%20extracellular%20levels%20of%20serotonin%2C%20and%20protein%20expression%20levels%20were%20assessed%20by%20immunofluorescence%2C%20in%20vivo%20dialysis%2C%20and%20Western%20blotting%2C%20respectively.%20IGN%20was%20rescued%20by%20infusing%20glucose%20into%20the%20portal%20vein%20of%20IGN-deficient%20mice.%20%26lt%3Bb%26gt%3B%26lt%3Bi%26gt%3BResults%3A%26lt%3B%5C%2Fi%26gt%3B%26lt%3B%5C%2Fb%26gt%3B%20We%20show%20here%20that%20both%20fiber-%20and%20protein-enriched%20diets%20exert%20beneficial%20actions%20on%20anxiety-like%20and%20depressive-like%20behaviors.%20These%20benefits%20do%20not%20occur%20in%20mice%20lacking%20IGN.%20Consistently%2C%20IGN-deficient%20mice%20display%20hallmarks%20of%20depressive-like%20disorders%2C%20including%20decreased%20hippocampal%20neurogenesis%2C%20basal%20hyperactivity%2C%20and%20deregulation%20of%20the%20hypothalamic-pituitary-adrenal%20axis%2C%20which%20are%20associated%20with%20increased%20expression%20of%20the%20precursor%20of%20corticotropin-releasing%20hormone%20in%20the%20hypothalamus%20and%20decreased%20expression%20of%20the%20glucocorticoid%20receptor%20in%20the%20hippocampus.%20These%20neurobiological%20alterations%20are%20corrected%20by%20portal%20glucose%20infusion%20mimicking%20IGN.%20%26lt%3Bb%26gt%3B%26lt%3Bi%26gt%3BConclusion%3A%26lt%3B%5C%2Fi%26gt%3B%26lt%3B%5C%2Fb%26gt%3B%20IGN%20translates%20nutritional%20information%2C%20allowing%20the%20brain%20to%20finely%20coordinate%20energy%20metabolism%20and%20behavior.%22%2C%22date%22%3A%222021%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1159%5C%2F000514289%22%2C%22ISSN%22%3A%220028-3835%2C%201423-0194%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fkarger.com%5C%2Farticle%5C%2Fdoi%5C%2F10.1159%5C%2F000514289%22%2C%22collections%22%3A%5B%22K5DKASFS%22%2C%22LUQ7ZPMM%22%2C%22FKFCWCTY%22%5D%2C%22dateModified%22%3A%222025-06-13T09%3A02%3A17Z%22%7D%7D%2C%7B%22key%22%3A%22JB5WJJFX%22%2C%22library%22%3A%7B%22id%22%3A6024536%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Soty%20et%20al.%22%2C%22parsedDate%22%3A%222021%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%26lt%3Bdiv%20class%3D%26quot%3Bcsl-bib-body%26quot%3B%20style%3D%26quot%3Bline-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%26quot%3B%26gt%3B%5Cn%20%20%26lt%3Bdiv%20class%3D%26quot%3Bcsl-entry%26quot%3B%26gt%3BSoty%2C%20M.%2C%20Vily-Petit%2C%20J.%2C%20Castellanos-Jankiewicz%2C%20A.%2C%20Guzman-Quevedo%2C%20O.%2C%20Raffin%2C%20M.%2C%20Clark%2C%20S.%2C%20Silva%2C%20M.%2C%20Gautier-Stein%2C%20A.%2C%20Cota%2C%20D.%2C%20%26amp%3B%20Mithieux%2C%20G.%20%282021%29.%20Calcitonin%20Gene-Related%20Peptide-Induced%20Phosphorylation%20of%20STAT3%20in%20Arcuate%20Neurons%20Is%20a%20Link%20in%20the%20Metabolic%20Benefits%20of%20Portal%20Glucose.%20%26lt%3Bi%26gt%3BNeuroendocrinology%26lt%3B%5C%2Fi%26gt%3B%2C%20%26lt%3Bi%26gt%3B111%26lt%3B%5C%2Fi%26gt%3B%286%29%2C%20555%26%23×2013%3B567.%20%26lt%3Ba%20class%3D%26%23039%3Bzp-DOIURL%26%23039%3B%20href%3D%26%23039%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1159%5C%2F000509230%26%23039%3B%26gt%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1159%5C%2F000509230%26lt%3B%5C%2Fa%26gt%3B%26lt%3B%5C%2Fdiv%26gt%3B%5Cn%26lt%3B%5C%2Fdiv%26gt%3B%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Calcitonin%20Gene-Related%20Peptide-Induced%20Phosphorylation%20of%20STAT3%20in%20Arcuate%20Neurons%20Is%20a%20Link%20in%20the%20Metabolic%20Benefits%20of%20Portal%20Glucose%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Maud%22%2C%22lastName%22%3A%22Soty%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Justine%22%2C%22lastName%22%3A%22Vily-Petit%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ashley%22%2C%22lastName%22%3A%22Castellanos-Jankiewicz%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Omar%22%2C%22lastName%22%3A%22Guzman-Quevedo%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Margaux%22%2C%22lastName%22%3A%22Raffin%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Samantha%22%2C%22lastName%22%3A%22Clark%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Marine%22%2C%22lastName%22%3A%22Silva%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Amandine%22%2C%22lastName%22%3A%22Gautier-Stein%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Daniela%22%2C%22lastName%22%3A%22Cota%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Gilles%22%2C%22lastName%22%3A%22Mithieux%22%7D%5D%2C%22abstractNote%22%3A%22%26lt%3Bb%26gt%3B%26lt%3Bi%26gt%3BIntroduction%3A%26lt%3B%5C%2Fi%26gt%3B%26lt%3B%5C%2Fb%26gt%3B%20Intestinal%20gluconeogenesis%20%28IGN%29%20exerts%20metabolic%20benefits%20in%20energy%20homeostasis%20via%20the%20neural%20sensing%20of%20portal%20glucose.%20%26lt%3Bb%26gt%3B%26lt%3Bi%26gt%3BObjective%3A%26lt%3B%5C%2Fi%26gt%3B%26lt%3B%5C%2Fb%26gt%3B%20The%20aim%20of%20this%20work%20was%20to%20determine%20central%20mechanisms%20involved%20in%20the%20effects%20of%20IGN%20on%20the%20control%20of%20energy%20homeostasis.%20%26lt%3Bb%26gt%3B%26lt%3Bi%26gt%3BMethods%3A%26lt%3B%5C%2Fi%26gt%3B%26lt%3B%5C%2Fb%26gt%3B%20We%20investigated%20the%20effects%20of%20glucose%20infusion%20into%20the%20portal%20vein%2C%20at%20a%20rate%20that%20mimics%20IGN%2C%20in%20conscious%20wild-type%2C%20leptin-deficient%20%26lt%3Bi%26gt%3BOb%5C%2FOb%26lt%3B%5C%2Fi%26gt%3B%20and%20calcitonin%20gene-related%20peptide%20%28CGRP%29-deficient%20mice.%20%26lt%3Bb%26gt%3B%26lt%3Bi%26gt%3BResults%3A%26lt%3B%5C%2Fi%26gt%3B%26lt%3B%5C%2Fb%26gt%3B%20We%20report%20that%20portal%20glucose%20infusion%20decreases%20food%20intake%20and%20plasma%20glucose%20and%20induces%20in%20the%20hypothalamic%20arcuate%20nucleus%20%28ARC%29%20the%20phosphorylation%20of%20STAT3%2C%20the%20classic%20intracellular%20messenger%20of%20leptin%20signaling.%20This%20notably%20takes%20place%20in%20POMC-expressing%20neurons.%20STAT3%20phosphorylation%20does%20not%20require%20leptin%2C%20since%20portal%20glucose%20effects%20are%20observed%20in%20leptin-deficient%20%26lt%3Bi%26gt%3BOb%5C%2FOb%26lt%3B%5C%2Fi%26gt%3B%20mice.%20We%20hypothesized%20that%20the%20portal%20glucose%20effects%20could%20require%20CGRP%2C%20a%20neuromediator%20previously%20suggested%20to%20suppress%20hunger.%20In%20line%20with%20this%20hypothesis%2C%20neither%20the%20metabolic%20benefits%20nor%20the%20phosphorylation%20of%20STAT3%20in%20the%20ARC%20take%20place%20upon%20portal%20glucose%20infusion%20in%20CGRP-deficient%20mice.%20Moreover%2C%20intracerebroventricular%20injection%20of%20CGRP%20activates%20hypothalamic%20phosphorylation%20of%20STAT3%20in%20mice%2C%20and%20CGRP%20does%20the%20same%20in%20hypothalamic%20cells.%20Finally%2C%20no%20metabolic%20benefit%20of%20dietary%20fibers%20%28known%20to%20depend%20on%20the%20induction%20of%20IGN%29%2C%20takes%20place%20in%20CGRP-deficient%20mice.%20%26lt%3Bb%26gt%3B%26lt%3Bi%26gt%3BConclusions%3A%26lt%3B%5C%2Fi%26gt%3B%26lt%3B%5C%2Fb%26gt%3B%20CGRP-induced%20phosphorylation%20of%20STAT3%20in%20the%20ARC%20is%20part%20of%20the%20neural%20chain%20determining%20the%20hunger-modulating%20and%20glucose-lowering%20effects%20of%20IGN%5C%2Fportal%20glucose.%22%2C%22date%22%3A%222021%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1159%5C%2F000509230%22%2C%22ISSN%22%3A%220028-3835%2C%201423-0194%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fkarger.com%5C%2Farticle%5C%2Fdoi%5C%2F10.1159%5C%2F000509230%22%2C%22collections%22%3A%5B%22K5DKASFS%22%2C%22LUQ7ZPMM%22%2C%22FKFCWCTY%22%5D%2C%22dateModified%22%3A%222025-06-13T09%3A01%3A52Z%22%7D%7D%2C%7B%22key%22%3A%22UEDTLULF%22%2C%22library%22%3A%7B%22id%22%3A6024536%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Vily-Petit%20et%20al.%22%2C%22parsedDate%22%3A%222022-01-26%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%26lt%3Bdiv%20class%3D%26quot%3Bcsl-bib-body%26quot%3B%20style%3D%26quot%3Bline-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%26quot%3B%26gt%3B%5Cn%20%20%26lt%3Bdiv%20class%3D%26quot%3Bcsl-entry%26quot%3B%26gt%3BVily-Petit%2C%20J.%2C%20Barataud%2C%20A.%2C%20Zitoun%2C%20C.%2C%20Gautier-Stein%2C%20A.%2C%20Serino%2C%20M.%2C%20%26amp%3B%20Mithieux%2C%20G.%20%282022%29.%20Intestinal%20gluconeogenesis%20shapes%20gut%20microbiota%2C%20fecal%20and%20urine%20metabolome%20in%20mice%20with%20gastric%20bypass%20surgery.%20%26lt%3Bi%26gt%3BScientific%20Reports%26lt%3B%5C%2Fi%26gt%3B%2C%20%26lt%3Bi%26gt%3B12%26lt%3B%5C%2Fi%26gt%3B%281%29%2C%201415.%20%26lt%3Ba%20class%3D%26%23039%3Bzp-DOIURL%26%23039%3B%20href%3D%26%23039%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1038%5C%2Fs41598-022-04902-y%26%23039%3B%26gt%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1038%5C%2Fs41598-022-04902-y%26lt%3B%5C%2Fa%26gt%3B%26lt%3B%5C%2Fdiv%26gt%3B%5Cn%26lt%3B%5C%2Fdiv%26gt%3B%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Intestinal%20gluconeogenesis%20shapes%20gut%20microbiota%2C%20fecal%20and%20urine%20metabolome%20in%20mice%20with%20gastric%20bypass%20surgery%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Justine%22%2C%22lastName%22%3A%22Vily-Petit%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Aude%22%2C%22lastName%22%3A%22Barataud%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Carine%22%2C%22lastName%22%3A%22Zitoun%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Amandine%22%2C%22lastName%22%3A%22Gautier-Stein%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Matteo%22%2C%22lastName%22%3A%22Serino%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Gilles%22%2C%22lastName%22%3A%22Mithieux%22%7D%5D%2C%22abstractNote%22%3A%22Abstract%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20Intestinal%20gluconeogenesis%20%28IGN%29%2C%20gastric%20bypass%20%28GBP%29%20and%20gut%20microbiota%20positively%20regulate%20glucose%20homeostasis%20and%20diet-induced%20dysmetabolism.%20GBP%20modulates%20gut%20microbiota%2C%20whether%20IGN%20could%20shape%20it%20has%20not%20been%20investigated.%20We%20studied%20gut%20microbiota%20and%20microbiome%20in%20wild%20type%20and%20IGN-deficient%20mice%2C%20undergoing%20GBP%20or%20not%2C%20and%20fed%20on%20either%20a%20normal%20chow%20%28NC%29%20or%20a%20high-fat%5C%2Fhigh-sucrose%20%28HFHS%29%20diet.%20We%20also%20studied%20fecal%20and%20urine%20metabolome%20in%20NC-fed%20mice.%20IGN%20and%20GBP%20had%20a%20different%20effect%20on%20the%20gut%20microbiota%20of%20mice%20fed%20with%20NC%20and%20HFHS%20diet.%20IGN%20inactivation%20increased%20abundance%20of%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20Deltaproteobacteria%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20on%20NC%20and%20of%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20Proteobacteria%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20such%20as%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20Helicobacter%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20on%20HFHS%20diet.%20GBP%20increased%20abundance%20of%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20Firmicutes%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20and%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20Proteobacteria%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20on%20NC-fed%20WT%20mice%20and%20of%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20Firmicutes%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%2C%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20Bacteroidetes%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20and%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20Proteobacteria%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20on%20HFHS-fed%20WT%20mice.%20The%20combined%20effect%20of%20IGN%20inactivation%20and%20GBP%20increased%20abundance%20of%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20Actinobacteria%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20on%20NC%20and%20the%20abundance%20of%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20Enterococcaceae%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20and%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20Enterobacteriaceae%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20on%20HFHS%20diet.%20A%20reduction%20was%20observed%20in%20the%20amounf%20of%20short-chain%20fatty%20acids%20in%20fecal%20%28by%20GBP%29%20and%20in%20both%20fecal%20and%20urine%20%28by%20IGN%20inactivation%29%20metabolome.%20IGN%20and%20GBP%2C%20separately%20or%20combined%2C%20shape%20gut%20microbiota%20and%20microbiome%20on%20NC-%20and%20HFHS-fed%20mice%2C%20and%20modify%20fecal%20and%20urine%20metabolome.%22%2C%22date%22%3A%222022-01-26%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1038%5C%2Fs41598-022-04902-y%22%2C%22ISSN%22%3A%222045-2322%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fwww.nature.com%5C%2Farticles%5C%2Fs41598-022-04902-y%22%2C%22collections%22%3A%5B%22LUQ7ZPMM%22%2C%22FKFCWCTY%22%5D%2C%22dateModified%22%3A%222025-06-13T09%3A01%3A40Z%22%7D%7D%2C%7B%22key%22%3A%22BAJG2PC9%22%2C%22library%22%3A%7B%22id%22%3A6024536%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Vily-Petit%20et%20al.%22%2C%22parsedDate%22%3A%222024-06-07%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%26lt%3Bdiv%20class%3D%26quot%3Bcsl-bib-body%26quot%3B%20style%3D%26quot%3Bline-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%26quot%3B%26gt%3B%5Cn%20%20%26lt%3Bdiv%20class%3D%26quot%3Bcsl-entry%26quot%3B%26gt%3BVily-Petit%2C%20J.%2C%20Taki%2C%20A.%2C%20Sinet%2C%20F.%2C%20Soty%2C%20M.%2C%20Guiard%2C%20B.%2C%20Zemdegs%2C%20J.%2C%20Malleret%2C%20G.%2C%20Stefanutti%2C%20A.%2C%20Mithieux%2C%20G.%2C%20%26amp%3B%20Gautier-Stein%2C%20A.%20%282024%29.%20Absence%20of%20the%20Peptide%20Transporter%201%20Induces%20a%20Prediabetic%20and%20Depressive-Like%20Phenotype%20in%20Mice.%20%26lt%3Bi%26gt%3BNeuroendocrinology%26lt%3B%5C%2Fi%26gt%3B%2C%201%26%23×2013%3B16.%20%26lt%3Ba%20class%3D%26%23039%3Bzp-DOIURL%26%23039%3B%20href%3D%26%23039%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1159%5C%2F000539499%26%23039%3B%26gt%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1159%5C%2F000539499%26lt%3B%5C%2Fa%26gt%3B%26lt%3B%5C%2Fdiv%26gt%3B%5Cn%26lt%3B%5C%2Fdiv%26gt%3B%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Absence%20of%20the%20Peptide%20Transporter%201%20Induces%20a%20Prediabetic%20and%20Depressive-Like%20Phenotype%20in%20Mice%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Justine%22%2C%22lastName%22%3A%22Vily-Petit%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Amelie%22%2C%22lastName%22%3A%22Taki%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Flore%22%2C%22lastName%22%3A%22Sinet%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Maud%22%2C%22lastName%22%3A%22Soty%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Bruno%22%2C%22lastName%22%3A%22Guiard%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Juliane%22%2C%22lastName%22%3A%22Zemdegs%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Gael%22%2C%22lastName%22%3A%22Malleret%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Anne%22%2C%22lastName%22%3A%22Stefanutti%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Gilles%22%2C%22lastName%22%3A%22Mithieux%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Amandine%22%2C%22lastName%22%3A%22Gautier-Stein%22%7D%5D%2C%22abstractNote%22%3A%22%26lt%3Bb%26gt%3B%26lt%3Bi%26gt%3BIntroduction%3A%26lt%3B%5C%2Fi%26gt%3B%26lt%3B%5C%2Fb%26gt%3B%20Protein-enriched%20diets%20improve%20glycemic%20control%20in%20diabetes%20or%20emotional%20behavior%20in%20depressive%20patients.%20In%20mice%2C%20these%20benefits%20depend%20on%20intestinal%20gluconeogenesis%20activation%20by%20di-%5C%2Ftripeptides.%20Intestinal%20di-%5C%2Ftripeptides%20absorption%20is%20carried%20out%20by%20the%20peptide%20transporter%201%2C%20PEPT1.%20The%20lack%20of%20PEPT1%20might%20thus%20alter%20glucose%20and%20emotional%20balance.%20%26lt%3Bb%26gt%3B%26lt%3Bi%26gt%3BMethods%3A%26lt%3B%5C%2Fi%26gt%3B%26lt%3B%5C%2Fb%26gt%3B%20To%20determine%20the%20effects%20of%20PEPT1%20deficiency%20under%20standard%20dietary%20conditions%20or%20during%20a%20dietary%20challenge%20known%20to%20promote%20both%20metabolic%20and%20cognitive%20dysfunction%2C%20insulin%20sensitivity%2C%20anxiety%2C%20and%20depressive-like%20traits%2C%20hippocampal%20serotonin%20%285-HT%29%20and%20insulin%20signaling%20pathway%20were%20measured%20in%20wild-type%20%28WT%29%20and%20Pept1%26lt%3Bsup%26gt%3B%5Cu2212%5C%2F%5Cu2212%26lt%3B%5C%2Fsup%26gt%3B%20mice%20fed%20either%20a%20chow%20or%20a%20high-fat%20high-sucrose%20%28HF-HS%29%20diet.%20%26lt%3Bb%26gt%3B%26lt%3Bi%26gt%3BResults%3A%26lt%3B%5C%2Fi%26gt%3B%26lt%3B%5C%2Fb%26gt%3B%20Pept1%26lt%3Bsup%26gt%3B%5Cu2212%5C%2F%5Cu2212%26lt%3B%5C%2Fsup%26gt%3B%20mice%20exhibited%20slight%20defects%20in%20insulin%20sensitivity%20and%20emotional%20behavior%2C%20which%20were%20aggravated%20by%20an%20HF-HS%20diet.%20Pept1%26lt%3Bsup%26gt%3B%5Cu2212%5C%2F%5Cu2212%26lt%3B%5C%2Fsup%26gt%3B%20mice%20fed%20a%20chow%20diet%20had%20lower%20hippocampal%205-HT%20levels%20and%20exhibited%20cerebral%20insulin%20resistance%20under%20HF-HS%20diet.%20These%20defects%20were%20independent%20of%20intestinal%20gluconeogenesis%20but%20might%20be%20linked%20to%20increased%20plasma%20amino%20acids%20levels.%20%26lt%3Bb%26gt%3B%26lt%3Bi%26gt%3BConclusion%3A%26lt%3B%5C%2Fi%26gt%3B%26lt%3B%5C%2Fb%26gt%3B%20Pept1%26lt%3Bsup%26gt%3B%5Cu2212%5C%2F%5Cu2212%26lt%3B%5C%2Fsup%26gt%3B%20mice%20develop%20prediabetic%20and%20depressive-like%20traits%20and%20could%20thus%20be%20used%20to%20develop%20strategies%20to%20prevent%20or%20cure%20both%20diseases.%22%2C%22date%22%3A%222024-6-7%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1159%5C%2F000539499%22%2C%22ISSN%22%3A%220028-3835%2C%201423-0194%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fkarger.com%5C%2Farticle%5C%2Fdoi%5C%2F10.1159%5C%2F000539499%22%2C%22collections%22%3A%5B%22LUQ7ZPMM%22%2C%22FKFCWCTY%22%5D%2C%22dateModified%22%3A%222025-06-13T09%3A01%3A24Z%22%7D%7D%2C%7B%22key%22%3A%22H57KUWIC%22%2C%22library%22%3A%7B%22id%22%3A6024536%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Cao%20et%20al.%22%2C%22parsedDate%22%3A%222021-05-25%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%26lt%3Bdiv%20class%3D%26quot%3Bcsl-bib-body%26quot%3B%20style%3D%26quot%3Bline-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%26quot%3B%26gt%3B%5Cn%20%20%26lt%3Bdiv%20class%3D%26quot%3Bcsl-entry%26quot%3B%26gt%3BCao%2C%20J.%2C%20Choi%2C%20M.%2C%20Guadagnin%2C%20E.%2C%20Soty%2C%20M.%2C%20Silva%2C%20M.%2C%20Verzieux%2C%20V.%2C%20Weisser%2C%20E.%2C%20Markel%2C%20A.%2C%20Zhuo%2C%20J.%2C%20Liang%2C%20S.%2C%20Yin%2C%20L.%2C%20Frassetto%2C%20A.%2C%20Graham%2C%20A.-R.%2C%20Burke%2C%20K.%2C%20Ketova%2C%20T.%2C%20Mihai%2C%20C.%2C%20Zalinger%2C%20Z.%2C%20Levy%2C%20B.%2C%20Besin%2C%20G.%2C%20%26%23×2026%3B%20Giangrande%2C%20P.%20H.%20%282021%29.%20mRNA%20therapy%20restores%20euglycemia%20and%20prevents%20liver%20tumors%20in%20murine%20model%20of%20glycogen%20storage%20disease.%20%26lt%3Bi%26gt%3BNature%20Communications%26lt%3B%5C%2Fi%26gt%3B%2C%20%26lt%3Bi%26gt%3B12%26lt%3B%5C%2Fi%26gt%3B%281%29%2C%203090.%20%26lt%3Ba%20class%3D%26%23039%3Bzp-DOIURL%26%23039%3B%20href%3D%26%23039%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1038%5C%2Fs41467-021-23318-2%26%23039%3B%26gt%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1038%5C%2Fs41467-021-23318-2%26lt%3B%5C%2Fa%26gt%3B%26lt%3B%5C%2Fdiv%26gt%3B%5Cn%26lt%3B%5C%2Fdiv%26gt%3B%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22mRNA%20therapy%20restores%20euglycemia%20and%20prevents%20liver%20tumors%20in%20murine%20model%20of%20glycogen%20storage%20disease%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jingsong%22%2C%22lastName%22%3A%22Cao%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Minjung%22%2C%22lastName%22%3A%22Choi%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Eleonora%22%2C%22lastName%22%3A%22Guadagnin%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Maud%22%2C%22lastName%22%3A%22Soty%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Marine%22%2C%22lastName%22%3A%22Silva%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Vincent%22%2C%22lastName%22%3A%22Verzieux%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Edward%22%2C%22lastName%22%3A%22Weisser%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Arianna%22%2C%22lastName%22%3A%22Markel%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jenny%22%2C%22lastName%22%3A%22Zhuo%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Shi%22%2C%22lastName%22%3A%22Liang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ling%22%2C%22lastName%22%3A%22Yin%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Andrea%22%2C%22lastName%22%3A%22Frassetto%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Anne-Renee%22%2C%22lastName%22%3A%22Graham%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Kristine%22%2C%22lastName%22%3A%22Burke%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Tatiana%22%2C%22lastName%22%3A%22Ketova%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Cosmin%22%2C%22lastName%22%3A%22Mihai%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Zach%22%2C%22lastName%22%3A%22Zalinger%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Becca%22%2C%22lastName%22%3A%22Levy%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Gilles%22%2C%22lastName%22%3A%22Besin%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Meredith%22%2C%22lastName%22%3A%22Wolfrom%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Barbara%22%2C%22lastName%22%3A%22Tran%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Christopher%22%2C%22lastName%22%3A%22Tunkey%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Erik%22%2C%22lastName%22%3A%22Owen%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Joe%22%2C%22lastName%22%3A%22Sarkis%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Athanasios%22%2C%22lastName%22%3A%22Dousis%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Vladimir%22%2C%22lastName%22%3A%22Presnyak%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Christopher%22%2C%22lastName%22%3A%22Pepin%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Wei%22%2C%22lastName%22%3A%22Zheng%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Lei%22%2C%22lastName%22%3A%22Ci%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Marjie%22%2C%22lastName%22%3A%22Hard%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Edward%22%2C%22lastName%22%3A%22Miracco%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Lisa%22%2C%22lastName%22%3A%22Rice%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Vi%22%2C%22lastName%22%3A%22Nguyen%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Mike%22%2C%22lastName%22%3A%22Zimmer%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Uma%22%2C%22lastName%22%3A%22Rajarajacholan%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Patrick%20F.%22%2C%22lastName%22%3A%22Finn%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Gilles%22%2C%22lastName%22%3A%22Mithieux%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Fabienne%22%2C%22lastName%22%3A%22Rajas%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Paolo%20G.%20V.%22%2C%22lastName%22%3A%22Martini%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Paloma%20H.%22%2C%22lastName%22%3A%22Giangrande%22%7D%5D%2C%22abstractNote%22%3A%22Abstract%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20Glycogen%20Storage%20Disease%201a%20%28GSD1a%29%20is%20a%20rare%2C%20inherited%20metabolic%20disorder%20caused%20by%20deficiency%20of%20glucose%206-phosphatase%20%28G6Pase-%5Cu03b1%29.%20G6Pase-%5Cu03b1%20is%20critical%20for%20maintaining%20interprandial%20euglycemia.%20GSD1a%20patients%20exhibit%20life-threatening%20hypoglycemia%20and%20long-term%20liver%20complications%20including%20hepatocellular%20adenomas%20%28HCAs%29%20and%20carcinomas%20%28HCCs%29.%20There%20is%20no%20treatment%20for%20GSD1a%20and%20the%20current%20standard-of-care%20for%20managing%20hypoglycemia%20%28Glycosade%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cu00ae%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%5C%2Fmodified%20cornstarch%29%20fails%20to%20prevent%20HCA%5C%2FHCC%20risk.%20Therapeutic%20modalities%20such%20as%20enzyme%20replacement%20therapy%20and%20gene%20therapy%20are%20not%20ideal%20options%20for%20patients%20due%20to%20challenges%20in%20drug-delivery%2C%20efficacy%2C%20and%20safety.%20To%20develop%20a%20new%20treatment%20for%20GSD1a%20capable%20of%20addressing%20both%20the%20life-threatening%20hypoglycemia%20and%20HCA%5C%2FHCC%20risk%2C%20we%20encapsulated%20engineered%20mRNAs%20encoding%20human%20G6Pase-%5Cu03b1%20in%20lipid%20nanoparticles.%20We%20demonstrate%20the%20efficacy%20and%20safety%20of%20our%20approach%20in%20a%20preclinical%20murine%20model%20that%20phenotypically%20resembles%20the%20human%20condition%2C%20thus%20presenting%20a%20potential%20therapy%20that%20could%20have%20a%20significant%20therapeutic%20impact%20on%20the%20treatment%20of%20GSD1a.%22%2C%22date%22%3A%222021-05-25%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1038%5C%2Fs41467-021-23318-2%22%2C%22ISSN%22%3A%222041-1723%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fwww.nature.com%5C%2Farticles%5C%2Fs41467-021-23318-2%22%2C%22collections%22%3A%5B%22LUQ7ZPMM%22%2C%22FKFCWCTY%22%5D%2C%22dateModified%22%3A%222025-06-13T09%3A00%3A47Z%22%7D%7D%5D%7D
Monteillet, L., Labrune, P., Hochuli, M., Do Cao, J., Tortereau, A., Miliano, A. C., Ardon-Zitoun, C., Duchampt, A., Silva, M., Verzieux, V., Mithieux, G., & Rajas, F. (2022). Cellular and metabolic effects of renin-angiotensin system blockade on glycogen storage disease type I nephropathy.
Human Molecular Genetics,
31(6), 914–928.
https://doi.org/10.1093/hmg/ddab297
Gautier-Stein, A., Chilloux, J., Soty, M., Thorens, B., Place, C., Zitoun, C., Duchampt, A., Da Costa, L., Rajas, F., Lamaze, C., & Mithieux, G. (2023). A caveolin-1 dependent glucose-6-phosphatase trafficking contributes to hepatic glucose production.
Molecular Metabolism,
70, 101700.
https://doi.org/10.1016/j.molmet.2023.101700
Estrada-Meza, J., Videlo, J., Bron, C., Saint-Béat, C., Silva, M., Duboeuf, F., Peyruchaud, O., Rajas, F., Mithieux, G., & Gautier-Stein, A. (2021). Tamoxifen Treatment in the Neonatal Period Affects Glucose Homeostasis in Adult Mice in a Sex-Dependent Manner.
Endocrinology,
162(7), bqab098.
https://doi.org/10.1210/endocr/bqab098
Vily‐Petit, J., Soty‐Roca, M., Silva, M., Micoud, M., Evrard, F., Bron, C., Raffin, M., Beiroa, D., Nogueiras, R., Roussel, D., Gautier‐Stein, A., Rajas, F., Cota, D., & Mithieux, G. (2024). Antiobesity effects of intestinal gluconeogenesis are mediated by the brown adipose tissue sympathetic nervous system.
Obesity,
32(4), 710–722.
https://doi.org/10.1002/oby.23985
Rajas, F., Dentin, R., Cannella Miliano, A., Silva, M., Raffin, M., Levavasseur, F., Gautier-Stein, A., Postic, C., & Mithieux, G. (2021). The absence of hepatic glucose-6 phosphatase/ChREBP couple is incompatible with survival in mice.
Molecular Metabolism,
43, 101108.
https://doi.org/10.1016/j.molmet.2020.101108
Sinet, F., Soty, M., Zemdegs, J., Guiard, B., Estrada, J., Malleret, G., Silva, M., Mithieux, G., & Gautier-Stein, A. (2021). Dietary Fibers and Proteins Modulate Behavior via the Activation of Intestinal Gluconeogenesis.
Neuroendocrinology,
111(12), 1249–1265.
https://doi.org/10.1159/000514289
Soty, M., Vily-Petit, J., Castellanos-Jankiewicz, A., Guzman-Quevedo, O., Raffin, M., Clark, S., Silva, M., Gautier-Stein, A., Cota, D., & Mithieux, G. (2021). Calcitonin Gene-Related Peptide-Induced Phosphorylation of STAT3 in Arcuate Neurons Is a Link in the Metabolic Benefits of Portal Glucose.
Neuroendocrinology,
111(6), 555–567.
https://doi.org/10.1159/000509230
Vily-Petit, J., Barataud, A., Zitoun, C., Gautier-Stein, A., Serino, M., & Mithieux, G. (2022). Intestinal gluconeogenesis shapes gut microbiota, fecal and urine metabolome in mice with gastric bypass surgery.
Scientific Reports,
12(1), 1415.
https://doi.org/10.1038/s41598-022-04902-y
Vily-Petit, J., Taki, A., Sinet, F., Soty, M., Guiard, B., Zemdegs, J., Malleret, G., Stefanutti, A., Mithieux, G., & Gautier-Stein, A. (2024). Absence of the Peptide Transporter 1 Induces a Prediabetic and Depressive-Like Phenotype in Mice.
Neuroendocrinology, 1–16.
https://doi.org/10.1159/000539499
Cao, J., Choi, M., Guadagnin, E., Soty, M., Silva, M., Verzieux, V., Weisser, E., Markel, A., Zhuo, J., Liang, S., Yin, L., Frassetto, A., Graham, A.-R., Burke, K., Ketova, T., Mihai, C., Zalinger, Z., Levy, B., Besin, G., … Giangrande, P. H. (2021). mRNA therapy restores euglycemia and prevents liver tumors in murine model of glycogen storage disease.
Nature Communications,
12(1), 3090.
https://doi.org/10.1038/s41467-021-23318-2