Diabetes Metab J.  2019 Oct;43(5):659-674. 10.4093/dmj.2018.0196.

Low-Frequency Intermittent Hypoxia Suppresses Subcutaneous Adipogenesis and Induces Macrophage Polarization in Lean Mice

Affiliations
  • 1Department of Medicine, The University of Hong Kong Li Ka Shing Faculty of Medicine, Hong Kong. msmip@hku.hk
  • 2Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China.
  • 3Research Centre of Heart, Brain, Hormone and Healthy Aging, The University of Hong Kong Li Ka Shing Faculty of Medicine, Hong Kong.
  • 4Department of Pharmacology & Pharmacy, The University of Hong Kong Li Ka Shing Faculty of Medicine, Hong Kong.

Abstract

BACKGROUND
The relationship between obstructive sleep apnoea (OSA) and metabolic disorders is complex and highly associated. The impairment of adipogenic capacity in pre-adipocytes may promote adipocyte hypertrophy and increase the risk of further metabolic dysfunction. We hypothesize that intermittent hypoxia (IH), as a pathophysiologic feature of OSA, may regulate adipogenesis by promoting macrophage polarization.
METHODS
Male C57BL/6N mice were exposed to either IH (240 seconds of 10% Oâ‚‚ followed by 120 seconds of 21% Oâ‚‚, i.e., 10 cycles/hour) or intermittent normoxia (IN) for 6 weeks. Stromal-vascular fractions derived from subcutaneous (SUB-SVF) and visceral (VIS-SVF) adipose tissues were cultured and differentiated. Conditioned media from cultured RAW 264.7 macrophages after air (Raw) or IH exposure (Raw-IH) were incubated with SUB-SVF during adipogenic differentiation.
RESULTS
Adipogenic differentiation of SUB-SVF but not VIS-SVF from IH-exposed mice was significantly downregulated in comparison with that derived from IN-exposed mice. IH-exposed mice compared to IN-exposed mice showed induction of hypertrophic adipocytes and increased preferential infiltration of M1 macrophages in subcutaneous adipose tissue (SAT) compared to visceral adipose tissue. Complementary in vitro analysis demonstrated that Raw-IH media significantly enhanced inhibition of adipogenesis of SUB-SVF compared to Raw media, in agreement with corresponding gene expression levels of differentiation-associated markers and adipogenic transcription factors.
CONCLUSION
Low frequency IH exposure impaired adipogenesis of SAT in lean mice, and macrophage polarization may be a potential mechanism for the impaired adipogenesis.

Keyword

Adipogenesis; Inflammation; Hypoxia; Macrophages

MeSH Terms

Adipocytes
Adipogenesis*
Animals
Anoxia*
Culture Media, Conditioned
Gene Expression
Humans
Hypertrophy
In Vitro Techniques
Inflammation
Intra-Abdominal Fat
Macrophages*
Male
Mice*
Subcutaneous Fat
Transcription Factors
Culture Media, Conditioned
Transcription Factors
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