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Importance of mitochondrial Dynamin Related Protein 1 (DRP1) in hypothalamic glucose sensitivity in rats.
MedLine Citation:
PMID:  22229526     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
AIMS: Hypothalamic mitochondrial reactive oxygen species (mROS)-mediated signaling has been recently shown to be involved in the regulation of energy homeostasis. However, the upstream signals that control this mechanism have not yet been determined. Here, we hypothesized that glucose induced mitochondrial fission plays a significant role in mROS-dependent hypothalamic glucose sensing. RESULTS: Glucose triggered translocation of fission protein DRP1 to mitochondria was firstly investigated in vivo in hypothalamus. Thus we show that intracarotid glucose injection induces the recruitment of DRP1 to VMH mitochondria in vivo. Then, expression was transiently knocked down by intra-ventro medial hypothalamus (VMH) DRP1 siRNA (siDRP1) injection. 72h post siRNA injection, brain intracarotid glucose induced insulin secretion and VMH glucose infusion-induced refeeding decrease were measured, as well as mROS production. The SiDRP1 rats decreased mROS and impaired intracarotid glucose injection-induced insulin secretion. In addition, the VMH glucose infusion-induced refeeding decrease was lost in siDRP1 rats. Finally, mitochondrial function was evaluated by oxygen consumption measurements after DRP1 knock down. Although hypothalamic mitochondrial respiration was not modified in the resting state, substrate-driven respiration was impaired in siDRP1 rats and associated with an alteration of the coupling mechanism. INNOVATION AND CONCLUSION: Collectively, our results suggest that glucose-induced DRP1-dependent mitochondrial fission is an upstream regulator for mROS signaling and consequently, a key mechanism in hypothalamic glucose sensing. Thus, for the first time, we demonstrate the involvement of DRP1 in physiological regulation of brain glucose induced insulin secretion and food intake inhibition. Such involvement implies DRP1 dependent mROS production.
Authors:
Lionel Carneiro; Camille Allard; Christophe Guissard; Xavier Fioramonti; Cécile Tourrel-Cuzin; Danielle Bailbe; Corinne Barreau; Géraldine Offer; Emmanuelle Nedelec; Bénédicte Salin; Michel Rigoulet; Pascale Belenguer; Luc Pénicaud; Corinne Leloup
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-1-9
Journal Detail:
Title:  Antioxidants & redox signaling     Volume:  -     ISSN:  1557-7716     ISO Abbreviation:  -     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-1-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100888899     Medline TA:  Antioxid Redox Signal     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
UMR CNRS 6265 - INRA 1324- Université de Bourgogne, Centre des Sciences du Goût et de l'Alimentation CSGA, Dijon, France; lionel_carneiro@etu.u-bourgogne.fr.
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