Activation of the AMP activated protein kinase by short-chain fatty acids is the main mechanism underlying the beneficial effect of a high fiber diet on the metabolic syndrome

Med Hypotheses. 2010 Jan;74(1):123-6. doi: 10.1016/j.mehy.2009.07.022. Epub 2009 Aug 7.


The metabolic syndrome, a cluster of conditions including abdominal obesity, insulin resistance, dyslipidemia, and elevated blood pressure, is a natural consequence of over nutrition and a sedentary lifestyle. The prevalence of the metabolic syndrome has increased to epidemic proportions in the world. The exact pathogenesis of the metabolic syndrome remains unclear, but it is known to be a complex interaction between genetic, metabolic, and environmental factors. Promotion of physical activity and dietary management are still the main methods for the prevention and management of the metabolic syndrome. Numerous experimental and clinical studies have demonstrated the beneficial effects of high fiber diet on the metabolic syndrome. The principal beneficial effects of a fiber-rich diet in these patients are: prevention of obesity, improved glucose levels, and control of the profile of blood lipids. Dietary fiber may also favor the control of arterial blood pressure. How dietary fiber exerts its beneficial effects on the metabolic syndrome is not well understood. AMP activated protein kinase (AMPK) functions as a major cellular fuel gauge and a master regulator of metabolic homeostasis. Several lines of evidence suggest that AMPK can be activated by short-chain fatty acids (SCFA) either directly or indirectly. It is our hypothesis that the main mechanism underlying the beneficial effect of a high fiber diet on the metabolic syndrome is the increased SCFA production in the colon leading to a higher concentration of SCFA in the portal vein, which activates the AMPK in the liver.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism*
  • Animals
  • Diet
  • Dietary Fiber / therapeutic use
  • Fatty Acids / metabolism
  • Fatty Acids, Volatile / metabolism*
  • Homeostasis
  • Humans
  • Insulin Resistance
  • Liver / metabolism
  • Metabolic Syndrome / enzymology*
  • Mice
  • Models, Biological
  • Models, Theoretical
  • Rats


  • Dietary Fiber
  • Fatty Acids
  • Fatty Acids, Volatile
  • AMP-Activated Protein Kinases