Fatty Acid Transporter CD36 Mediates Hypothalamic Effect of Fatty Acids on Food Intake in Rats.

Valentine S. Moullé (1) , Christelle Le Foll (2) , Philippe Erwann (1) , Nadim Kassis (1) , Claude Rouch (1) , Nicolas Marsollier (1) , Bui Linh-Chi (1) , Christophe Guissard (3) , Julien Dairou (1) , Anne Lorsignol (3) , Luc Pénicaud (4) , Barry E. Levin (2) , Céline Cruciani-Guglielmacci (1) , Christophe Magnan (1)

1 BFA (UMR_8251 / U1133) - Unité de Biologie Fonctionnelle et Adaptative
2 Department of Neurology and Neurosciences
3 STROMALab
4 CSGA - Centre des Sciences du Goût et de l'Alimentation [Dijon]

Variations in plasma fatty acid (FA) concentrations are detected by FA sensing neurons in specific brain areas such as the hypothalamus. These neurons play a physiological role in the control of food intake and the regulation of hepatic glucose production. Le Foll et al. previously showed in vitro that at least 50% of the FA sensing in ventromedial hypothalamic (VMH) neurons is attributable to the interaction of long chain FA with FA translocase/CD36 (CD36). The present work assessed whether in vivo effects of hypothalamic FA sensing might be partly mediated by CD36 or intracellular events such as acylCoA synthesis or β-oxidation. To that end, a catheter was implanted in the carotid artery toward the brain in male Wistar rats. After 1 wk recovery, animals were food-deprived for 5 h, then 10 min infusions of triglyceride emulsion, Intralipid +/- heparin (IL, ILH, respectively) or saline/heparin (SH) were carried out and food intake was assessed over the next 5 h. Experimental groups included: 1) Rats previously injected in ventromedian nucleus (VMN) with shRNA against CD36 or scrambled RNA; 2) Etomoxir (CPT1 inhibitor) or saline co-infused with ILH/SH; and 3) Triacsin C (acylCoA synthase inhibitor) or saline co-infused with ILH/SH. ILH significantly lowered food intake during refeeding compared to SH (p<0.001). Five hours after refeeding, etomoxir did not affect this inhibitory effect of ILH on food intake while VMN CD36 depletion totally prevented it. Triacsin C also prevented ILH effects on food intake. In conclusion, the effect of FA to inhibit food intake is dependent on VMN CD36 and acylCoA synthesis but does not required FA oxidation.

Domaines: Neurobiologie

Valentine S. Moullé, Christelle Le Foll, Philippe Erwann, Nadim Kassis, Claude Rouch, et al.. Fatty Acid Transporter CD36 Mediates Hypothalamic Effect of Fatty Acids on Food Intake in Rats.. PLoS ONE, 2013, 8 (9), pp.e74021. ⟨10.1371/journal.pone.0074021⟩. ⟨hal-00865977⟩