PGC-1β-expressing POMC neurons mediate the effect of leptin on thermoregulation in the mouse

Sci Rep. 2020 Oct 15;10(1):16888. doi: 10.1038/s41598-020-73794-7.

Abstract

The arcuate nucleus (ARC) of the hypothalamus is a key regulator of food intake, brown adipose tissue (BAT) thermogenesis, and locomotor activity. Whole-body deficiency of the transcriptional coactivator peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1β (PGC-1β) disrupts mouse circadian locomotor activity and BAT-regulated thermogenesis, in association with altered gene expression at the central level. We examined whether PGC-1β expression in the ARC is required for proper energy balance and locomotor behavior by generating mice lacking the PGC-1β gene specifically in pro-opiomelanocortin (POMC) neurons. POMC neuron-specific deletion of PGC-1β did not impact locomotor behavior, food intake, body composition, energy fuel utilization and metabolic rate in fed, 24-h fasted and 24-h refed conditions. In contrast, in the fed state, deletion of PGC-1β in POMC cells elevated core body temperature during the nighttime period. Importantly, this higher body temperature is not associated with changes in BAT function and gene expression. Conversely, we provide evidence that mice lacking PGC-1β in POMC neurons are more sensitive to the effect of leptin on heat dissipation. Our data indicate that PGC-1β-expressing POMC neurons are part of a circuit controlling body temperature homeostasis and that PGC-1β function in these neurons is involved in the thermoregulatory effect of leptin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue, Brown / metabolism
  • Animals
  • Arcuate Nucleus of Hypothalamus / metabolism
  • Body Temperature Regulation / physiology*
  • Body Weight
  • Energy Metabolism / drug effects
  • Gene Expression Regulation
  • Hypothalamus / metabolism
  • Leptin / metabolism
  • Leptin / pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neurons / metabolism*
  • Neurons / physiology
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / metabolism*
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / physiology
  • Pro-Opiomelanocortin / metabolism
  • Pro-Opiomelanocortin / physiology
  • Thermogenesis / physiology
  • Transcription Factors / metabolism

Substances

  • Leptin
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Ppargc1a protein, mouse
  • Transcription Factors
  • Pro-Opiomelanocortin