title: Role for mitochondrial reactive oxygen species in brain lipid sensing: redox regulation of food intake.
abstract: 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.
authors.affiliation: Laboratoire de Neurobiologie, Plasticité Tissulaire et Métabolisme Energétique, Institut Louis Bugnard, Toulouse, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Benani
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Troy
authors.forename: Maria Carmen
authors.initials: MC
authors.lastname: Carmona
authors.forename: Xavier
authors.initials: X
authors.lastname: Fioramonti
authors.forename: Anne
authors.initials: A
authors.lastname: Lorsignol
authors.forename: Corinne
authors.initials: C
authors.lastname: Leloup
authors.forename: Louis
authors.initials: L
authors.lastname: Casteilla
authors.forename: Luc
authors.initials: L
authors.lastname: Pénicaud
mesh_terms: 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*
chemical_list: D008055:Lipids; D017382:Reactive Oxygen Species