ZFIN ID: ZDB-PUB-180510-10
Diet-Induced Growth Is Regulated via Acquired Leptin Resistance and Engages a Pomc-Somatostatin-Growth Hormone Circuit
Löhr, H., Hess, S., Pereira, M.M.A., Reinoß, P., Leibold, S., Schenkel, C., Wunderlich, C.M., Kloppenburg, P., Brüning, J.C., Hammerschmidt, M.
Date: 2018
Source: Cell Reports   23: 1728-1741 (Journal)
Registered Authors: Hammerschmidt, Matthias, Leibold, Sandra, Löhr, Heiko, Schenkel, Christel
Keywords: Pomc neuron, growth hormone, high-fat diet, leptin resistance, melanocortin system, mouse, obesity, somatic growth, somatostatin neuron, zebrafish
MeSH Terms:
  • Animals
  • Axons/drug effects
  • Axons/metabolism
  • Diet*
  • Growth Hormone/metabolism*
  • Growth and Development/drug effects*
  • Humans
  • Hypothalamus/drug effects
  • Hypothalamus/metabolism
  • Larva/drug effects
  • Larva/physiology
  • Leptin/pharmacology*
  • Lipid Metabolism/drug effects
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neural Inhibition/drug effects
  • Pituitary Gland, Anterior/drug effects
  • Pituitary Gland, Anterior/metabolism
  • Pro-Opiomelanocortin/metabolism*
  • Somatostatin/metabolism*
  • Zebrafish
  • alpha-MSH/metabolism
PubMed: 29742429 Full text @ Cell Rep.
Anorexigenic pro-opiomelanocortin (Pomc)/alpha-melanocyte stimulating hormone (αMSH) neurons of the hypothalamic melanocortin system function as key regulators of energy homeostasis, also controlling somatic growth across different species. However, the mechanisms of melanocortin-dependent growth control still remain ill-defined. Here, we reveal a thus-far-unrecognized structural and functional connection between Pomc neurons and the somatotropic hypothalamo-pituitary axis. Excessive feeding of larval zebrafish causes leptin resistance and reduced levels of the hypothalamic satiety mediator pomca. In turn, this leads to reduced activation of hypophysiotropic somatostatin (Sst)-neurons that express the melanocortin receptor Mc4r, elevated growth hormone (GH) expression in the pituitary, and enhanced somatic growth. Mc4r expression and αMSH responsiveness are conserved in Sst-expressing hypothalamic neurons of mice. Thus, acquired leptin resistance and attenuation of pomca transcription in response to excessive caloric intake may represent an ancient mechanism to promote somatic growth when food resources are plentiful.