A high-fat diet decreases AMPK activity in multiple tissues in the absence of hyperglycemia or systemic inflammation in rats

J Physiol Biochem. 2013 Jun;69(2):165-75. doi: 10.1007/s13105-012-0199-2. Epub 2012 Sep 2.


Consumption of a high-fat diet (HFD) in experimental animal models initiates a series of molecular events and outcomes, including insulin resistance and obesity, that mimic the metabolic syndrome in humans. The relationship among, and order of, the molecular events linking a diet high in fat to pathologies is often unclear. In the present study, we provide several novel insights into the relationship between a HFD and AMP-activated protein kinase (AMPK), a key regulator of cellular metabolism and whole-body energy balance. HFD substantially decreased the activities of both isoforms of AMPK in white adipose tissue, heart, and liver. These decreases in AMPK activity occurred in the absence of decreased AMPK transcription, systemic inflammation, hyperglycemia, or elevated levels of free fatty acids. The HFD-induced decrease in AMPK activity was associated with systemic insulin resistance and hyperleptinemia. In blood, >98 % of AMPK activity was localized in agranulocytes as the α1 isoform. In contrast to the solid tissues studied, AMPK activities were not altered by HFD in granulocytes or agranulocytes. We conclude that HFD-induced obesity causes a broad, non-tissue, or isoform-specific lowering of AMPK activity. Given the central position AMPK plays in whole-body energy balance, this decreased AMPK activity may play a previously unrecognized role in obesity and its associated pathologies.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • AMP-Activated Protein Kinases / metabolism*
  • Adipose Tissue, Brown / metabolism
  • Adipose Tissue, White / metabolism*
  • Animals
  • Diet, High-Fat*
  • Dietary Fats
  • Hyperglycemia / metabolism*
  • Inflammation / metabolism*
  • Inflammation / pathology
  • Male
  • Obesity / metabolism
  • Obesity / pathology
  • Organ Specificity
  • Rats
  • Rats, Sprague-Dawley


  • Dietary Fats
  • Prkaa1 protein, rat
  • Prkaa2 protein, rat
  • AMP-Activated Protein Kinases