Metabolic syndrome, hyperinsulinemia, and cancer

Am J Clin Nutr. 2007 Sep;86(3):s867-71. doi: 10.1093/ajcn/86.3.867S.


The term metabolic syndrome describes the association between obesity, insulin resistance, and the risk of several prominent chronic diseases, including cancer. The causal link between many of these components remains unexplained, however. What is clear are the events that precede the development of the syndrome itself. In animal models, a fat-supplemented diet causes 1) lipid deposition in adipose depots, 2) insulin resistance of liver and skeletal muscle, and 3) hyperinsulinemia. One hypothesis relating fat deposition and insulin resistance involves enhanced lipolysis in the visceral depot, which leads to an increase in free fatty acid (FFA) flux. Increased mass of stored lipid and insulin resistance of visceral adipocytes favors lipolysis. Additionally, hypersensitivity of visceral adipose cells to sympathetic nervous system stimulation leads to increased lipolysis in the obese state. However, little evidence is available for enhanced plasma FFA concentrations in the fasting state. We measured FFA concentrations over a 24-h day in obese animals and found that plasma FFAs are elevated in the middle of the night, peaking at 0300. Therefore, it is possible that nocturnal lipolysis increases exposure of liver and muscle to FFAs at night, thus causing insulin resistance, which may play a role in hyperinsulinemic compensation to insulin resistance. Nocturnal lipolysis secondary to sympathetic stimulation may not only cause insulin resistance but also be responsible for hyperinsulinemia by stimulating secretion and reducing clearance of insulin by the liver. The resulting syndrome-elevated nocturnal FFAs and elevated insulin-may synergize and increase the risk of some cancers. This possible scenario needs further study.

Publication types

  • Review

MeSH terms

  • Adipose Tissue / metabolism
  • Animals
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / metabolism
  • Fatty Acids, Nonesterified / blood
  • Humans
  • Hyperinsulinism / complications*
  • Hyperinsulinism / metabolism
  • Insulin Resistance
  • Lipolysis / physiology*
  • Metabolic Syndrome / complications*
  • Metabolic Syndrome / metabolism
  • Neoplasms / etiology*
  • Neoplasms / metabolism
  • Obesity / complications
  • Obesity / metabolism
  • Risk Factors
  • Sympathetic Nervous System / physiology


  • Fatty Acids, Nonesterified