Physiological and pathophysiological implications of lipid sensing in the brain

Diabetes Obes Metab. 2014 Sep;16 Suppl 1:49-55. doi: 10.1111/dom.12335.


Fatty acid (FA)-sensitive neurons are present in the brain, especially the hypothalamus, and play a key role in the neural control of energy homeostasis. Through neuronal output, FA may modulate feeding behaviour as well as insulin secretion and action. Subpopulations of neurons in the ventromedial and arcuate hypothalamic nuclei are selectively either inhibited or activated by FA. Molecular effectors of these FA effects probably include chloride or potassium ion channels. While intracellular metabolism and activation of the ATP-sensitive K⁺ channel appear to be necessary for some of the signalling effects of FA, at least half of the FA responses in ventromedial hypothalamic neurons are mediated by interaction with FAT/CD36, an FA transporter/receptor that does not require intracellular metabolism to activate downstream signalling. Thus, FA or their metabolites can modulate neuronal activity as a means of directly monitoring ongoing fuel availability by brain nutrient-sensing neurons involved in the regulation of energy and glucose homeostasis. Recently, the role of lipoprotein lipase in FA sensing has also been shown in animal models not only in hypothalamus, but also in hippocampus and striatum. Finally, FA overload might impair neural control of energy homeostasis through enhanced ceramide synthesis and may contribute to obesity and/or type 2 diabetes pathogenesis in predisposed subjects.

Keywords: FAT/CD36; energy balance; hypothalamus; potassium channel.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Appetite Regulation
  • CD36 Antigens / metabolism*
  • Corpus Striatum / cytology
  • Corpus Striatum / metabolism
  • Fatty Acids, Nonesterified / blood
  • Fatty Acids, Nonesterified / metabolism*
  • Feedback, Physiological*
  • Hippocampus / cytology
  • Hippocampus / metabolism
  • Humans
  • Lipid Metabolism*
  • Lipoprotein Lipase / metabolism
  • Models, Neurological*
  • Nerve Tissue Proteins / metabolism
  • Neurons / cytology
  • Neurons / metabolism*
  • Organ Specificity
  • Ventromedial Hypothalamic Nucleus / cytology
  • Ventromedial Hypothalamic Nucleus / metabolism*


  • CD36 Antigens
  • Fatty Acids, Nonesterified
  • Nerve Tissue Proteins
  • LPL protein, human
  • Lipoprotein Lipase