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

        Yan Wang,Mary Yuk Kwan Lee,Judith Choi Wo Mak,Mary Sau Man Ip 대한당뇨병학회 2019 Diabetes and Metabolism Journal Vol.43 No.5

        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 furthermetabolic dysfunction. We hypothesize that intermittent hypoxia (IH), as a pathophysiologic feature of OSA, may regulate adipogenesisby promoting macrophage polarization. Methods: Male C57BL/6N mice were exposed to either IH (240 seconds of 10% O2 followed by 120 seconds of 21% O2, 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 afterair (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 incomparison with that derived from IN-exposed mice. IH-exposed mice compared to IN-exposed mice showed induction of hypertrophicadipocytes and increased preferential infiltration of M1 macrophages in subcutaneous adipose tissue (SAT) comparedto visceral adipose tissue. Complementary in vitro analysis demonstrated that Raw-IH media significantly enhanced inhibition ofadipogenesis of SUB-SVF compared to Raw media, in agreement with corresponding gene expression levels of differentiation-associatedmarkers and adipogenic transcription factors. Conclusion: Low frequency IH exposure impaired adipogenesis of SAT in lean mice, and macrophage polarization may be a potentialmechanism for the impaired adipogenesis.

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