Growth hormone regulates neuroendocrine responses to weight loss via AgRP neurons

Nat Commun. 2019 Feb 8;10(1):662. doi: 10.1038/s41467-019-08607-1.


Weight loss triggers important metabolic responses to conserve energy, especially via the fall in leptin levels. Consequently, weight loss becomes increasingly difficult with weight regain commonly occurring in most dieters. Here we show that central growth hormone (GH) signaling also promotes neuroendocrine adaptations during food deprivation. GH activates agouti-related protein (AgRP) neurons and GH receptor (GHR) ablation in AgRP cells mitigates highly characteristic hypothalamic and metabolic adaptations induced by weight loss. Thus, the capacity of mice carrying an AgRP-specific GHR ablation to save energy during food deprivation is impaired, leading to increased fat loss. Additionally, administration of a clinically available GHR antagonist (pegvisomant) attenuates the fall of whole-body energy expenditure of food-deprived mice, similarly as seen by leptin treatment. Our findings indicate GH as a starvation signal that alerts the brain about energy deficiency, triggering key adaptive responses to conserve limited fuel stores.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agouti-Related Protein / genetics
  • Agouti-Related Protein / metabolism*
  • Animals
  • Body Weight / drug effects
  • Brain / drug effects
  • Brain / metabolism
  • Energy Metabolism / drug effects
  • Female
  • Growth Hormone / metabolism
  • Growth Hormone / pharmacology
  • Human Growth Hormone / analogs & derivatives
  • Human Growth Hormone / therapeutic use
  • Leptin / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, Somatotropin / genetics
  • Receptors, Somatotropin / metabolism*
  • Weight Loss / drug effects


  • Agouti-Related Protein
  • Leptin
  • Receptors, Somatotropin
  • Human Growth Hormone
  • Growth Hormone
  • pegvisomant