EJE PRIZE 2017: Hypothalamic AMPK: a golden target against obesity?

Eur J Endocrinol. 2017 May;176(5):R235-R246. doi: 10.1530/EJE-16-0927. Epub 2017 Feb 23.

Abstract

AMP-activated protein kinase (AMPK) is a cellular gauge that is activated under conditions, such as low energy, increasing energy production and reducing energy waste. Centrally, the AMPK pathway is a canonical route regulating energy homeostasis, by integrating peripheral signals, such as hormones and metabolites, with neuronal networks. Current evidence links hypothalamic AMPK with feeding, brown adipose tissue (BAT) thermogenesis and browning of white adipose tissue (WAT), as well as muscle metabolism, hepatic function and glucose homeostasis. The relevance of these data is interesting from a therapeutic point of view as several agents with potential anti-obesity and/or antidiabetic effects, some currently in clinical use, such as nicotine, metformin and liraglutide are known to act through AMPK, either peripherally or centrally. Furthermore, the orexigenic and weight-gaining effects of the worldwide use of antipsychotic drugs (APDs), such as olanzapine, are also mediated by hypothalamic AMPK. Overall, this evidence makes hypothalamic AMPK signaling an interesting target for the drug development, with its potential for controlling both sides of the energy balance equation, namely feeding and energy expenditure through defined metabolic pathways.

Publication types

  • Review

MeSH terms

  • AMP-Activated Protein Kinases / antagonists & inhibitors
  • AMP-Activated Protein Kinases / metabolism*
  • Adipose Tissue, Brown / drug effects
  • Adipose Tissue, Brown / metabolism
  • Adipose Tissue, White / drug effects
  • Adipose Tissue, White / metabolism
  • Animals
  • Anti-Obesity Agents / administration & dosage
  • Anti-Obesity Agents / metabolism*
  • Awards and Prizes*
  • Drug Delivery Systems / methods
  • Drug Delivery Systems / trends
  • Energy Metabolism / drug effects
  • Energy Metabolism / physiology
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / metabolism
  • Hypothalamus / drug effects
  • Hypothalamus / metabolism*
  • Obesity / drug therapy*
  • Obesity / metabolism*

Substances

  • Anti-Obesity Agents
  • Hypoglycemic Agents
  • AMP-Activated Protein Kinases