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Judith Choi Wo Mak  (Mak JCW) 1 Article
Pathophysiology
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
Diabetes Metab J. 2019;43(5):659-674.   Published online April 23, 2019
DOI: https://doi.org/10.4093/dmj.2018.0196
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  • 6 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   
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% 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 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.

Citations

Citations to this article as recorded by  
  • Obstructive sleep apnea hypopnea syndrome and vascular lesions: An update on what we currently know
    Zhenyu Mao, Pengdou Zheng, Xiaoyan Zhu, Lingling Wang, Fengqin Zhang, Huiguo Liu, Hai Li, Ling Zhou, Wei Liu
    Sleep Medicine.2024; 119: 296.     CrossRef
  • Melatonin attenuates chronic intermittent hypoxia-induced intestinal barrier dysfunction in mice
    Xinyi Li, Fan Wang, Zhenfei Gao, Weijun Huang, Xiaoman Zhang, Feng Liu, Hongliang Yi, Jian Guan, Xiaolin Wu, Huajun Xu, Shankai Yin
    Microbiological Research.2023; 276: 127480.     CrossRef
  • Clinical outcomes and plaque characteristics in patients with coronary artery disease and concomitant sleep-disordered breathing treated by continuous positive airway pressure
    Kazuhiro Fujiyoshi, Taiki Tojo, Yoshiyasu Minami, Kohki Ishida, Miwa Ishida, Ken-ichiro Wakabayashi, Takayuki Inomata, Junya Ako
    Sleep Medicine.2023; 101: 543.     CrossRef
  • Potential Pathophysiological Pathways in the Complex Relationships between OSA and Cancer
    Manuel Sánchez-de-la-Torre, Carolina Cubillos, Olivia J. Veatch, Francisco Garcia-Rio, David Gozal, Miguel Angel Martinez-Garcia
    Cancers.2023; 15(4): 1061.     CrossRef
  • Effects of Chronic Intermittent Hypoxia and Chronic Sleep Fragmentation on Gut Microbiome, Serum Metabolome, Liver and Adipose Tissue Morphology
    Fan Wang, Juanjuan Zou, Huajun Xu, Weijun Huang, Xiaoman Zhang, Zhicheng Wei, Xinyi Li, Yupu Liu, Jianyin Zou, Feng Liu, Huaming Zhu, Hongliang Yi, Jian Guan, Shankai Yin
    Frontiers in Endocrinology.2022;[Epub]     CrossRef
  • C‐X3‐C motif chemokine ligand 1/receptor 1 regulates the M1 polarization and chemotaxis of macrophages after hypoxia/reoxygenation injury
    Shuiming Guo, Lei Dong, Junhua Li, Yuetao Chen, Ying Yao, Rui Zeng, Nelli Shushakova, Hermann Haller, Gang Xu, Song Rong
    Chronic Diseases and Translational Medicine.2021; 7(4): 254.     CrossRef

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