Metabolic syndrome: a brain disease

Can J Physiol Pharmacol. 2012 Sep;90(9):1171-83. doi: 10.1139/y2012-122. Epub 2012 Aug 22.


Recent research indicates an association between brain dysfunction and the pathogenesis of metabolic syndrome. To investigate this, we created a Medline search (up to December 2011) of articles in PubMed. The results indicated that refined carbohydrates, saturated and total fat, high levels of ω-6 fatty acids, and low levels of ω-3 fatty acids and other long chain polyunsaturated fatty acids (PUFA), all in conjunction with sedentary behaviour and mental stress can predispose to inflammation. Increased sympathetic activity, with increased secretion of catecholamine, cortisol, and serotonin can cause oxidative stress, which may damage the arcuate nucleus as well as the hypothalamus and macrophages, and the liver may release pro-inflammatory cytokines. These, in conjunction with an underlying deficiency in long chain PUFA, may damage the arcuate nucleus as well as neuropeptide-Y and pro-opiomelanocortin neurons and insulin receptors in the brain, especially during fetal life, infancy, and childhood, resulting in their dysfunction. Of the fatty acids in the brain, 30%-50% are long chain PUFA, which are incorporated in the cell membrane phospholipids. Hence, ω-3 fatty acids, which are also known to enhance parasympathetic activity and increase the secretion of anti-inflammatory cytokines interleukin (IL)-4 and IL-10 as well as acetylcholine in the hippocampus, may be protective. Therefore, treatment with ω-3 fatty acids may be applied for the prevention of metabolic syndrome.

Publication types

  • Review

MeSH terms

  • Aging / metabolism
  • Aging / psychology
  • Appetite Regulation / physiology
  • Arcuate Nucleus of Hypothalamus / metabolism
  • Brain / drug effects
  • Brain / immunology
  • Brain / metabolism
  • Brain Diseases / complications
  • Brain Diseases / immunology
  • Brain Diseases / metabolism*
  • Brain Diseases / prevention & control
  • Cytokines / metabolism
  • Fatty Acids, Omega-3 / metabolism
  • Fatty Acids, Omega-3 / therapeutic use
  • Feeding Behavior / physiology
  • Humans
  • Liver / drug effects
  • Liver / immunology
  • Liver / metabolism
  • Metabolic Syndrome / complications
  • Metabolic Syndrome / immunology
  • Metabolic Syndrome / metabolism*
  • Metabolic Syndrome / prevention & control
  • Receptor, Insulin / metabolism
  • Risk Factors


  • Cytokines
  • Fatty Acids, Omega-3
  • Receptor, Insulin