Downregulation of uncoupling protein-1 mRNA expression and hypoadiponectinemia in a mouse model of sleep apnea

Sleep Breath. 2014 Sep;18(3):541-8. doi: 10.1007/s11325-013-0916-2. Epub 2013 Dec 14.

Abstract

Purpose: The knowledge on the effect of intermittent hypoxia on adipose tissue-mediated processes is incipient. The aim of the present study was to assess the effect of a sleep apnea model on a limited set of specific molecular, biochemical, histological, and behavioral parameters of adipose tissue function.

Methods: Mice were exposed to either intermittent hypoxia or sham hypoxia during 8 h a day for 37 days. Uncoupling protein-1 expression in brown adipose tissue was measured by real-time PCR and immunohistochemistry. Digital quantification of adipose cells and immunohistochemistry of uncoupling protein-1 were performed to determine cell dimensions, positive area, and staining intensity. Serum levels of leptin, adiponectin, and cortisol were measured by ELISA.

Results: In comparison with the control group, animals in the hypoxia group had significantly lower chow ingestion, weight gain, and smaller white and brown adipocytes on histological examination. Adiponectin levels were also lower in the hypoxia group. Uncoupling protein-1 mRNA was abolished in the mice exposed to hypoxia; accordingly, fewer cells positive for uncoupling protein-1 and lighter staining intensity were observed in brown adipocytes.

Conclusions: An experimental model of sleep apnea produced changes in uncoupling protein-1 expression and adiponectin levels. These results confirm previous findings on the response of brown adipose tissue to intermittent hypoxia and indicate a yet-unknown interference of intermittent hypoxia on energy control, which may participate in the propensity to weight gain observed in patients with sleep apnea. Brown adipose tissue activity in this patient population needs to be further investigated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiponectin / blood
  • Adiponectin / deficiency*
  • Adiponectin / genetics
  • Adipose Tissue, Brown / metabolism
  • Animals
  • Disease Models, Animal*
  • Down-Regulation / genetics
  • Energy Metabolism / genetics
  • Energy Metabolism / physiology
  • Gene Expression Regulation / genetics*
  • Hydrocortisone / blood
  • Hypoxia / genetics
  • Ion Channels / genetics*
  • Male
  • Metabolism, Inborn Errors / blood*
  • Metabolism, Inborn Errors / genetics*
  • Mice
  • Mice, Inbred BALB C
  • Mitochondrial Proteins / genetics*
  • RNA, Messenger / genetics*
  • Sleep Apnea, Obstructive / blood*
  • Sleep Apnea, Obstructive / genetics*
  • Uncoupling Protein 1

Substances

  • Adiponectin
  • Ion Channels
  • Mitochondrial Proteins
  • RNA, Messenger
  • Ucp1 protein, mouse
  • Uncoupling Protein 1
  • Hydrocortisone

Supplementary concepts

  • Hypoadiponectinemia