Insulin signaling to hepatic lipid metabolism in health and disease

Crit Rev Biochem Mol Biol. 2011 Jun;46(3):200-15. doi: 10.3109/10409238.2011.562481. Epub 2011 Apr 5.

Abstract

The increasing prevalence of overnutrition and reduced activity has led to a worldwide epidemic of obesity. In many cases, this is associated with insulin resistance, an inability of the hormone to direct its physiological actions appropriately. A number of disease states accompany insulin resistance such as type 2 diabetes mellitus, the metabolic syndrome, and non-alcoholic fatty liver disease. Though the pathways by which insulin controls hepatic glucose output have been of intense study in recent years, considerably less attention has been devoted to how lipid metabolism is regulated. Thus, both the proximal signaling pathways as well as the more distal targets of insulin remain uncertain. In this review, we consider the signaling pathways by which insulin controls the synthesis and accumulation of lipids in the mammalian liver and, in particular, how this might lead to abnormal triglyceride deposition in liver during insulin-resistant states.

Publication types

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

MeSH terms

  • Dyslipidemias / metabolism
  • Fatty Liver / epidemiology
  • Fatty Liver / metabolism
  • Fatty Liver / physiopathology
  • Glucose / chemistry
  • Glucose / metabolism*
  • Humans
  • Insulin / chemistry*
  • Insulin / metabolism*
  • Insulin Resistance
  • Lipid Metabolism*
  • Lipids / biosynthesis
  • Lipids / chemistry
  • Liver / metabolism*
  • Liver / pathology*
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / metabolism
  • Oncogene Protein v-akt / chemistry
  • Oncogene Protein v-akt / metabolism
  • Receptor, Insulin / chemistry
  • Receptor, Insulin / metabolism
  • Signal Transduction*
  • Sterol Regulatory Element Binding Protein 1 / chemistry
  • Sterol Regulatory Element Binding Protein 1 / metabolism
  • Transcription Factors / chemistry
  • Transcription Factors / metabolism
  • Triglycerides / metabolism

Substances

  • Insulin
  • Lipids
  • Mlxipl protein, mouse
  • Nuclear Proteins
  • Sterol Regulatory Element Binding Protein 1
  • Transcription Factors
  • Triglycerides
  • Receptor, Insulin
  • Oncogene Protein v-akt
  • Glucose