Role for mitochondrial reactive oxygen species in brain lipid sensing: redox regulation of food intake.
The ability for the brain to sense peripheral fuel availability is mainly accomplished within the hypothalamus, which detects ongoing systemic nutrients and adjusts food intake and peripheral metabolism as needed. Here, we hypothesized that mitochondrial reactive oxygen species (ROS) could trigger sensing of nutrients within the hypothalamus. For this purpose, we induced acute hypertriglyceridemia in rats and examined the function of mitochondria in the hypothalamus. Hypertriglyceridemia led to a rapid increase in the mitochondrial respiration in the ventral hypothalamus together with a transient production of ROS. Cerebral inhibition of fatty acids-CoA mitochondrial uptake prevented the hypertriglyceridemia-stimulated ROS production, indicating that ROS derived from mitochondrial metabolism. The hypertriglyceridemia-stimulated ROS production was associated with change in the intracellular redox state without any noxious cytotoxic effects, suggesting that ROS function acutely as signaling molecules. Moreover, cerebral inhibition of hypertriglyceridemia-stimulated ROS production fully abolished the satiety related to the hypertriglyceridemia, suggesting that hypothalamic ROS production was required to restrain food intake during hypertriglyceridemia. Finally, we found that fasting disrupted the hypertriglyceridemia-stimulated ROS production, indicating that the redox mechanism of brain nutrient sensing could be modulated under physiological conditions. Altogether, these findings support the role of mitochondrial ROS as molecular actors implied in brain nutrient sensing.
Benani
Alexandre
A
Laboratoire de Neurobiologie, Plasticité Tissulaire et Métabolisme Energétique, Institut Louis Bugnard, Toulouse, France.
Troy
Stéphanie
S
Carmona
Maria Carmen
MC
Fioramonti
Xavier
X
Lorsignol
Anne
A
Leloup
Corinne
C
Casteilla
Louis
L
Pénicaud
Luc
L
D000818:Animals; D001921:Brain / Q000502:physiology*; D002149:Energy Intake; D015228:Hypertriglyceridemia / Q000378:metabolism; D008055:Lipids / Q000502:physiology*; D008297:Male; D008928:Mitochondria / Q000502:physiology*; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*
D008055:Lipids; D017382:Reactive Oxygen Species