Importance of mitochondrial dynamin-related protein 1 in hypothalamic glucose sensitivity in rats

Lionel Carneiro, Camille Allard, Christophe Guissard, Xavier Fioramonti, Cécile Tourrel-Cuzin, Danielle Bailbé, Corinne Barreau, Géraldine Offer, Emmanuelle Nédelec, Bénédicte Salin, Michel Rigoulet, Pascale Belenguer, Luc Pénicaud, Corinne Leloup
Antioxidants & Redox Signaling. 2012-08-01; 17(3): 433-444
DOI: 10.1089/ars.2011.4254

https://www.bordeaux-neurocampus.fr/12041

1. Antioxid Redox Signal. 2012 Aug 1;17(3):433-44. doi: 10.1089/ars.2011.4254.
Epub 2012 Mar 6.

Importance of mitochondrial dynamin-related protein 1 in hypothalamic glucose
sensitivity in rats.

Carneiro L(1), Allard C, Guissard C, Fioramonti X, Tourrel-Cuzin C, Bailbé D,
Barreau C, Offer G, Nédelec E, Salin B, Rigoulet M, Belenguer P, Pénicaud L,
Leloup C.

Author information:
(1)Centre des Sciences du Goût et de l’Alimentation (CSGA), Université de
Bourgogne, Dijon, France.

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 hypothesize that glucose-induced mitochondrial
fission plays a significant role in mROS-dependent hypothalamic glucose sensing.
RESULTS: Glucose-triggered translocation of the fission protein dynamin-related
protein 1 (DRP1) to mitochondria was first 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-ventromedial hypothalamus (VMH) DRP1 siRNA (siDRP1) injection. 72 h
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.