Key result
Global sod3 knockout in mice and SOD3 silencing in human adipocytes increased triglyceride accumulation, obesity, and insulin resistance, demonstrating its protective role in lipid metabolism.
Why the study?
The expression and regulatory role of SOD3 in adipocytes and adipose tissue were not fully understood.
SOD3 is identified as a protective factor secreted by adipocytes that mitigates high-fat diet-induced obesity, inflammation, and insulin resistance.
SOD3 may mitigate diet-induced obesity and insulin resistance; animal data leave open its therapeutic relevance in humans.
Aims: To study the expression and regulatory role of SOD3 in adipocytes and adipose tissue. Results: SOD3 expression was determined in various tissues of adult C57BL/6J mice, human adipose tissue and epididymal adipose tissue, subcutaneous adipose tissue and brown adipose tissue of high-fat diet (HFD)-induced obese mice. SOD3 expression and release were evaluated in adipocytes differentiated from primary human preadipocytes and murine bone marrow-derived mesenchymal stem cells (BM-MSCs). The regulatory role for SOD3 was determined by SOD3 lentivirus knockdown in human adipocytes and global sod3 knockout (KO) mice. SOD3 was expressed at high levels in white adipose tissue, and adipocytes were the main cells expressing SOD3 in adipose tissue. SOD3 expression was significantly elevated in adipose tissue of HFD-fed mice. Moreover, SOD3 expression and release were markedly increased in differentiated human adipocytes and adipocytes differentiated from mouse BM-MSCs compared with undifferentiated cells. In addition, SOD3 silencing in human adipocytes increased expression of genes involved in lipid metabolic pathways such as PPARγ and SREBP1c and promoted the accumulation of triglycerides. Finally, global sod3 KO mice were more obese and insulin resistant with enlarged adipose tissue and increased triglyceride accumulation. Innovation: Our data showed that SOD3 is secreted from adipocytes and regulates lipid metabolism in adipose tissue. This important discovery may open up new avenues of research for the cytoprotective role of SOD3 in obesity and its associated metabolic disorders. Conclusion: SOD3 is a protective factor secreted by adipocytes in response to HFD-induced obesity and regulates adipose tissue lipid metabolism.
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Gao et al. (2019) studied High-fat diet-induced obesity, inflammation, and insulin resistance. SOD3 knockdown/knockout vs. Control/wild-type was evaluated on Obesity, insulin resistance, and triglyceride accumulation. Global sod3 knockout in mice and SOD3 silencing in human adipocytes increased triglyceride accumulation, obesity, and insulin resistance, demonstrating its protective role in lipid metabolism.
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