The effects of extracellular matrix on beige adipogenesis in subcutaneous fat
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Adipose tissue is an organ that plays an important role in energy storage, nutritional balance and thermogenesis. White and brown adipose tissues have distinct cell morphology and metabolic functions. White adipose tissue (WAT) with unilocular lipid droplets serves as a major site of energy storage, while brown adipose tissue (BAT) with multilocular lipid droplets plays an important role in thermogenesis via a mitochondrial protein, uncoupling protein 1 (UCP1). These cells are derived from mesenchymal stem cells (MSCs). Newly discovered beige adipocytes are derived from the same MSC precursors as WAT but resemble BAT due to expression of UCP1. Due to side effects of drugs for treating obesity, activation of UCP1 positive beige adipocytes in WAT has become a new therapeutic target. The interaction of extracellular matrix (ECM) with integrin was found to regulate cell specification of mesenchymal stem cells (MSCs) via intracellular signaling. However, the role of individual ECM proteins in beige adipogenesis in WAT remains unknown. Therefore, we established a system for culturing stromal vascular fraction (SVF) cells from inguinal WAT on ECM protein coated plates and differentiating the cells into either white or beige adipocytes. We found that cells cultured on type I collagen had more round cell morphology and higher mRNA expression of thermogenic genes, UCP1 and type II iodothyronine deiodinase (DIO2),which was further enhanced in myocardin-related transcription factor A (MRTFA) knockout SVF cells. MRTFA has been reported to regulate beige adipogenesis in BMP-ROCK signaling pathway. Based on our data, we found that type I collagen-integrin signaling regulates beige adipogenesis by controlling the activity of MRTFA in MSCs. Our study has provided an insight into developing therapeutic drugs to enhance beige adipocytes formation in WAT for reducing obesity in the future.