FAT/CD36: A Major Regulator of Neuronal Fatty Acid Sensing and Energy Homeostasis in Rats and Mice
- Christelle Le Foll1⇑,
- Ambrose Dunn-Meynell2,
- Serguei Musatov3,
- Christophe Magnan4 and
- Barry E. Levin1,2
- 1Department of Neurology and Neurosciences, New Jersey Medical School, Newark, New Jersey
- 2VA Medical Center, East Orange, New Jersey
- 3Weill Cornell Medical College, New York, New York
- 4Unité de Biologie Fonctionnelle et Adaptative, Centre National de la Recherche Scientifique-Université Paris Diderot, Paris, France
- Corresponding author: Christelle Le Foll, .
Hypothalamic “metabolic-sensing” neurons sense glucose and fatty acids (FAs) and play an integral role in the regulation of glucose, energy homeostasis, and the development of obesity and diabetes. Using pharmacologic agents, we previously found that ∼50% of these neurons responded to oleic acid (OA) by using the FA translocator/receptor FAT/CD36 (CD36). For further elucidation of the role of CD36 in neuronal FA sensing, ventromedial hypothalamus (VMH) CD36 was depleted using adeno-associated viral (AAV) vector expressing CD36 short hairpin RNA (shRNA) in rats. Whereas their neuronal glucosensing was unaffected by CD36 depletion, the percent of neurons that responded to OA was decreased specifically in glucosensing neurons. A similar effect was seen in total-body CD36-knockout mice. Next, weanling rats were injected in the VMH with CD36 AAV shRNA. Despite significant VMH CD36 depletion, there was no effect on food intake, body weight gain, or total carcass adiposity on chow or 45% fat diets. However, VMH CD36–depleted rats did have increased plasma leptin and subcutaneous fat deposition and markedly abnormal glucose tolerance. These results demonstrate that CD36 is a critical factor in both VMH neuronal FA sensing and the regulation of energy and glucose homeostasis.
This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db12-1689/-/DC1.
- Received December 5, 2012.
- Accepted March 28, 2013.
- © 2013 by the American Diabetes Association.
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