PUBLICATION

Diet-Induced Growth Is Regulated via Acquired Leptin Resistance and Engages a Pomc-Somatostatin-Growth Hormone Circuit

Authors
Löhr, H., Hess, S., Pereira, M.M.A., Reinoß, P., Leibold, S., Schenkel, C., Wunderlich, C.M., Kloppenburg, P., Brüning, J.C., Hammerschmidt, M.
ID
ZDB-PUB-180510-10
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
  • Zebrafish
  • Diet*
  • Humans
  • Hypothalamus/drug effects
  • Hypothalamus/metabolism
  • Pro-Opiomelanocortin/metabolism*
  • Axons/drug effects
  • Axons/metabolism
  • Neural Inhibition/drug effects
  • Growth and Development/drug effects*
  • Pituitary Gland, Anterior/drug effects
  • Pituitary Gland, Anterior/metabolism
  • Mice, Inbred C57BL
  • Animals
  • Growth Hormone/metabolism*
  • Leptin/pharmacology*
  • Lipid Metabolism/drug effects
  • Somatostatin/metabolism*
  • alpha-MSH/metabolism
  • Larva/drug effects
  • Larva/physiology
  • Mice, Transgenic
(all 22)
PubMed
29742429 Full text @ Cell Rep.
Abstract
Anorexigenic pro-opiomelanocortin (Pomc)/alpha-melanocyte stimulating hormone (?MSH) 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 ?MSH 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.
Genes / Markers
Figures
Figure Gallery (11 images) / 2
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
No data available
Sequence Targeting Reagents
No data available
Fish
No data available
Antibodies
Orthology
No data available
Engineered Foreign Genes
Marker Marker Type Name
CFPEFGCFP
EGFPEFGEGFP
KALTA4EFGKALTA4
mCherryEFGmCherry
NTREFGNTR
1 - 5 of 5
Show
Mapping
Your Input Welcome
We welcome your input and comments. Please use this form to recommend updates to the information in ZFIN. We appreciate as much detail as possible and references as appropriate. We will review your comments promptly.
Citation
Löhr, H., Hess, S., Pereira, M.M.A., Reinoß, P., Leibold, S., Schenkel, C., Wunderlich, C.M., Kloppenburg, P., Brüning, J.C., Hammerschmidt, M. (2018) Diet-Induced Growth Is Regulated via Acquired Leptin Resistance and Engages a Pomc-Somatostatin-Growth Hormone Circuit. Cell Reports. 23:1728-1741.