The role of hepatic lipids in hepatic insulin resistance and type 2 diabetes

Nature. 2014 Jun 5;510(7503):84-91. doi: 10.1038/nature13478.


Non-alcoholic fatty liver disease and its downstream sequelae, hepatic insulin resistance and type 2 diabetes, are rapidly growing epidemics, which lead to increased morbidity and mortality rates, and soaring health-care costs. Developing interventions requires a comprehensive understanding of the mechanisms by which excess hepatic lipid develops and causes hepatic insulin resistance and type 2 diabetes. Proposed mechanisms implicate various lipid species, inflammatory signalling and other cellular modifications. Studies in mice and humans have elucidated a key role for hepatic diacylglycerol activation of protein kinase Cε in triggering hepatic insulin resistance. Therapeutic approaches based on this mechanism could alleviate the related epidemics of non-alcoholic fatty liver disease and type 2 diabetes.

Publication types

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

MeSH terms

  • Animals
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diglycerides / metabolism
  • Fatty Liver / drug therapy
  • Fatty Liver / metabolism
  • Humans
  • Hyperglycemia / metabolism
  • Insulin Resistance*
  • Lipid Metabolism*
  • Lipids* / biosynthesis
  • Lipodystrophy / metabolism
  • Lipogenesis
  • Liver / metabolism*
  • Muscle, Skeletal / metabolism
  • Non-alcoholic Fatty Liver Disease
  • Triglycerides / biosynthesis


  • 1,2-diacylglycerol
  • Diglycerides
  • Lipids
  • Triglycerides