Hypoxic adipocytes induce macrophages to release inflammatory cytokines that render skeletal muscle cells insulin resistant |
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| Affiliation: | 1. Department of Immunomlogy, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), NHC Key Laboratory of Hormones and Development (Tianjin Medical University), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, 300070, China;2. School of Pharmacy, Research Center of Basic Medical Science, Tianjin Medical University, Tianjin, 300070, China;3. Department of Ultrasound, Tianjin Hospital, Tianjin, 300211, China;4. Department of Endocrinology, Tianjin First Center Hospital, Tianjin, 300192, China;1. Flaum Eye Institute, USA;2. Department of Medicine, University of Rochester, Rochester, NY, USA;1. Department of Microbiology, Inha University School of Medicine, Incheon, 22212, South Korea;2. Division of Tumor Immunology, National Cancer Center, Goyang, 10408, South Korea;3. Department of Otorhinolaryngology-Head and Neck Surgery, Inha University School of Medicine, Incheon, 22212, South Korea;1. Department of Orthopedics, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, China;2. Central Laboratory, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, China |
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| Abstract: | Adipose tissue hypoxia occurs early in obesity and is associated with increased tissue macrophages and systemic inflammation that impacts muscle insulin responsiveness. We investigated how hypoxia interacted with adipocyte-macrophage crosstalk and inflammatory cytokine release, using co-culture and conditioned media (CM). Murine primary adipocytes from lean or obese mice were cultured under normoxic (21% O2) or hypoxic (1% O2) conditions. RAW264.7 macrophages were incubated under normoxic or hypoxic conditions with or without adipocyte conditioned media. Macrophage and adipocyte-macrophage co-culture CM were also collected. We found hypoxia did not elicit direct cytokine release from macrophages. However, adipocyte CM or adipocyte co-culture, synergistically stimulated TNFα and MCP-1 release from macrophages that was not further impacted by hypoxia. Exposure of muscle cells to elevated cytokines led to reduced insulin and muscle stress/inflammatory signaling. We conclude hypoxia or obesity induces release of inflammatory TNFα and MCP-1 from mice primary adipocytes but the two environmental conditions do not synergize to worsen macrophage signal transduction or insulin responsiveness. |
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| Keywords: | Obesity Hypoxia Insulin signaling Conditioned medium Inflammation |
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