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Scientific article
English

Direct leptin action on POMC neurons regulates glucose homeostasis and hepatic insulin sensitivity in mice

Contributors

Berglund, Eric D; Vianna, Claudia R; Donato, Jose (Jr); Kim, Mi Hwa; Chuang, Jen-Chieh; Lee, Charlotte E; Lauzon, Danielle A; Lin, Peagan; Brule, Laura J; Scott, Michael M; Coppari, Roberto; Elmquist, Joel K

Published in

The Journal of clinical investigation, vol. 122, no. 3, p. 1000-1009

Publication date

2012

Abstract

Leptin action on its receptor (LEPR) stimulates energy expenditure and reduces food intake, thereby lowering body weight. One leptin-sensitive target cell mediating these effects on energy balance is the proopiomelano-cortin (POMC) neuron. Recent evidence suggests that the action of leptin on POMC neurons regulates glucose homeostasis independently of its effects on energy balance. Here, we have dissected the physiological impact of direct leptin action on POMC neurons using a mouse model in which endogenous LEPR expression was prevented by a LoxP-flanked transcription blocker (loxTB), but could be reactivated by Cre recombinase. Mice homozygous for the Lepr(loxTB) allele were obese and exhibited defects characteristic of LEPR deficiency. Reexpression of LEPR only in POMC neurons in the arcuate nucleus of the hypothalamus did not reduce food intake, but partially normalized energy expenditure and modestly reduced body weight. Despite the moderate effects on energy balance and independent of changes in body weight, restoring LEPR in POMC neurons normalized blood glucose and ameliorated hepatic insulin resistance, hyperglucagonemia, and dyslipidemia. Collectively, these results demonstrate that direct leptin action on POMC neurons does not reduce food intake, but is sufficient to normalize glucose and glucagon levels in mice otherwise lacking LEPR.

Keywords

  • Animals
  • Arcuate Nucleus/metabolism
  • Body Weight
  • Energy Metabolism
  • Female
  • Glucagon/chemistry
  • Glucose/metabolism
  • Homeostasis
  • Homozygote
  • Hypothalamus/metabolism
  • Insulin/metabolism
  • Insulin Resistance
  • Leptin/metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neurons/metabolism
  • Pro-Opiomelanocortin/metabolism
  • Receptors, Leptin/metabolism

UNIGE affiliation entities

UNIGE research groups

Citation (ISO format)

BERGLUND, Eric D et al. Direct leptin action on POMC neurons regulates glucose homeostasis and hepatic insulin sensitivity in mice. In: The Journal of clinical investigation, 2012, vol. 122, n° 3, p. 1000–1009. doi: 10.1172/JCI59816

Main files (1)

Article (Published version)

Identifiers

Journal ISSN

0021-9738
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1downloads

Technical informations

Creation

04/11/2013 10:41:00

First validation

04/11/2013 10:41:00

Update

14/03/2023 20:44:10

Status update

14/03/2023 20:44:10

Last indexation

29/09/2025 10:36:00
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