Brain insulin signalling in metabolic homeostasis and disease

Nat Rev Endocrinol. 2021 Aug;17(8):468-483. doi: 10.1038/s41574-021-00498-x. Epub 2021 Jun 9.


Insulin signalling in the central nervous system regulates energy homeostasis by controlling metabolism in several organs and by coordinating organ crosstalk. Studies performed in rodents, non-human primates and humans over more than five decades using intracerebroventricular, direct hypothalamic or intranasal application of insulin provide evidence that brain insulin action might reduce food intake and, more importantly, regulates energy homeostasis by orchestrating nutrient partitioning. This Review discusses the metabolic pathways that are under the control of brain insulin action and explains how brain insulin resistance contributes to metabolic disease in obesity, the metabolic syndrome and type 2 diabetes mellitus.

Publication types

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

MeSH terms

  • Animals
  • Brain / metabolism*
  • Diabetes Mellitus, Type 2 / metabolism
  • Energy Metabolism / physiology*
  • Homeostasis / physiology
  • Humans
  • Insulin / metabolism*
  • Insulin Resistance / physiology
  • Metabolic Diseases / metabolism*
  • Metabolic Diseases / physiopathology
  • Metabolic Syndrome / metabolism
  • Signal Transduction / physiology


  • Insulin