Inhibitory effect of angiotensin Ⅱ on the brown fat differentiation of rat bone marrow mesenchymal stem cells
BACKGROUND:Bone marrow mesenchymal stem cells are one of the sources of adipocytes and express all renin-angiotensin system components,but the effect of angiotensin Ⅱ on bone marrow mesenchymal stem cell differentiation into brown adipose tissue is not clear.OBJECTIVE:To observe the effect of angiotensin Ⅱ on bone marrow mesenchymal stem cell differentiation into brown adipose tissue and investigate the role of angiotensin 1a receptor knockout in effect of angiotensin Ⅱ on bone marrow mesenchymal stem cell differentiation into brown adipocytes and its potential mechanisms.METHODS:After isolation and culture of bone marrow mesenchymal stem cells in wild-type and angiotensin 1a receptor knockout SD rats,the cells were cultured to the third generation and randomly divided into four groups:wild type group,knockout group,wild type+angiotensin Ⅱ group,and knockout+angiotensin Ⅱ group.The differentiation was induced in the brown fat induced differentiation medium for 14 days.Angiotensin Ⅱ(100 nmol/L)was added for intervention when the differentiation medium was changed each time in the latter two groups.Western blot assay,qRT-PCR,immunofluorescence,and other methods were used to detect the expression of induced differentiation,lipolysis,β oxidation,and mitochondrial biogenesis in brown fat.RESULTS AND CONCLUSION:Angiotensin Ⅱ could inhibit the browning of rat bone marrow mesenchymal stem cells.Knockout of angiotensin 1a receptor could improve the inhibitory effect of angiotensin Ⅱ on brown lipid formation of rat bone marrow mesenchymal stem cells by promoting lipolysis,enhancing fatty acid β oxidation,promoting mitochondrial biogenesis,and enhancing mitochondrial function.These findings provide new research directions and potential therapeutic targets for obesity treatment,revealing the important role of renin angiotensin systems in fat metabolism and its potential as a therapeutic target.
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