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Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis
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Hypothalamic POMC deficiency increases circulating adiponectin despite obesity.

Hui Yu1, Kavaljit H Chhabra2, Zoe Thompson1

  • 1Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, 48105, USA.

Molecular Metabolism
|April 4, 2020
PubMed
Summary
This summary is machine-generated.

Obesity does not always mean low adiponectin. POMC neurons regulate adiponectin through the sympathetic nervous system, revealing a new biological pathway.

Keywords:
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Area of Science:

  • Neuroendocrinology
  • Metabolic Syndrome Research
  • Adipose Tissue Biology

Background:

  • Obesity and metabolic syndrome are global health crises.
  • Pro-opiomelanocortin (POMC) neurons in the hypothalamus regulate appetite and body weight.
  • Adiponectin, a fat cell protein, typically correlates negatively with obesity.

Purpose of the Study:

  • To investigate the unexpected high adiponectin levels in obese ArcPomc-deficient mice.
  • To elucidate the mechanisms by which hypothalamic POMC regulates systemic adiponectin.

Main Methods:

  • Measured plasma adiponectin in ArcPomc-/- mice across various ages and conditions.
  • Assessed sympathetic nervous system activity and catecholamine levels.
  • Investigated adiponectin expression in specific adipose tissue depots.
  • Utilized genetic restoration of Pomc and pharmacological interventions.
  • Generated compound Adiopoq-/-:ArcPomc-/- mice for further analysis.

Main Results:

  • Obese ArcPomc-/- female mice exhibited paradoxically elevated plasma adiponectin levels.
  • High adiponectin persisted even after calorie restriction to normalize weight.
  • Genetic restoration of Pomc or melanotan II treatment reduced adiponectin.
  • Reduced sympathetic outflow to adipose tissue was observed in ArcPomc-/- mice.
  • Norepinephrine administration decreased adiponectin, while propranolol increased it.

Conclusions:

  • Hypothalamic POMC deficiency leads to elevated adiponectin, decoupling it from obesity.
  • A novel pathway involving POMC neurons and the sympathetic nervous system regulates adiponectin.
  • This finding challenges the direct correlation between adiposity and adiponectin levels.