Hypothalamic AMPK: A Canonical Regulator of Whole-Body Energy Balance

Nat Rev Endocrinol. 2016 Jul;12(7):421-32. doi: 10.1038/nrendo.2016.67. Epub 2016 May 20.

Abstract

AMP-activated protein kinase (AMPK) has a major role in the modulation of energy balance. AMPK is activated in conditions of low energy, increasing energy production and reducing energy consumption. The AMPK pathway is a canonical route regulating energy homeostasis by integrating peripheral signals, such as hormones and metabolites, with neuronal networks. Current evidence has implicated AMPK in the hypothalamus and hindbrain with feeding, brown adipose tissue thermogenesis and browning of white adipose tissue, through modulation of the sympathetic nervous system, as well as glucose homeostasis. Interestingly, several potential antiobesity and/or antidiabetic agents, some of which are currently in clinical use such as metformin and liraglutide, exert some of their actions by acting on AMPK. Furthermore, the orexigenic and weight-gain effects of commonly used antipsychotic drugs are also mediated by hypothalamic AMPK. Overall, this evidence suggests that hypothalamic AMPK signalling is an interesting target for drug development, but is this approach feasible? In this Review we discuss the current understanding of hypothalamic AMPK and its role in the central regulation of energy balance and metabolism.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / metabolism*
  • Adipose Tissue, Brown / metabolism*
  • Adipose Tissue, White / metabolism
  • Anti-Obesity Agents / therapeutic use
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / metabolism
  • Drug Discovery
  • Energy Metabolism*
  • Feeding Behavior*
  • Glucose / metabolism
  • Homeostasis
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Hypothalamus / metabolism*
  • Liraglutide / therapeutic use
  • Metformin / therapeutic use
  • Obesity / drug therapy
  • Obesity / metabolism*
  • Signal Transduction
  • Sympathetic Nervous System / metabolism*
  • Thermogenesis*

Substances

  • Anti-Obesity Agents
  • Hypoglycemic Agents
  • Liraglutide
  • Metformin
  • AMP-Activated Protein Kinases
  • Glucose