FAT/CD36: A major regulator of neuronal fatty acid sensing and energy homeostasis in rats and mice

  1. Barry E Levin1,2
  1. 1Dept Neurology and Neurosciences, NJ Medical School, Newark, NJ
  2. 2VA Med. Ctr., East Orange, NJ
  3. 3 Weill Cornell Medical College, New York, NY
  4. 4BFA CNRS-University Paris Diderot, Paris, France
  1. Corresponding author: Christelle Le Foll, lefollch{at}umdnj.edu

Abstract

Hypothalamic “metabolic sensing” neurons sense glucose, fatty acids (FA) and play an integral role in the regulation of glucose, energy homeostasis, the development of obesity and diabetes. Using pharmacologic agents, we previously found that ∼50% of these neurons responded to oleic acid, by utilizing the fatty acid (FA) translocator/receptor, FAT/CD36 (CD36). To further elucidate the role of CD36 in neuronal FA sensing, ventromedial hypothalamus (VMH) CD36 was depleted using adeno-associated viral (AAV) vector expressing CD36 shRNA in rats. While their neuronal glucosensing was unaffected by CD36 depletion, their percent of neurons that responded to oleic acid 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.

  • Received December 5, 2012.
  • Accepted March 27, 2013.

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