Ketone body 3-hydroxybutyrate enhances adipocyte function.

Ketone body 3-hydroxybutyrate enhances adipocyte function.
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DOI:
10.1038/s41598-022-14268-w
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发表时间:
2022-06-16
期刊:
影响因子:
4.6
通讯作者:
Shimomura I
Shimomura I
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Nishitani S;Fukuhara A;Tomita I;Kume S;Shin J;Okuno Y;Otsuki M;Maegawa H;Shimomura I

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包括3HBA在内的酮体是脂肪酸氧化的内源性产物,Hmgcs 2是生酮的第一限速酶。从数据库分析和体内、体外实验中,我们发现脂肪组织和脂肪细胞表达Hmgcs 2,脂肪细胞产生并分泌3HBA。用3HBA处理增强体内脂肪组织和体外脂肪细胞中抗氧化应激因子、PPARγ和脂肪生成因子的基因表达水平,同时降低ROS水平。敲低内源性Hmgcs 2可显著降低脂肪细胞中的3HBA水平,并降低抗氧化应激因子、PPARγ和脂肪生成因子的基因表达水平,同时增加ROS水平。相反,Hmgcs 2在脂肪细胞中的过表达增加了脂肪细胞的3HBA分泌,并增强了抗氧化应激因子、PPARγ和脂肪生成因子的基因表达水平。这些结果表明,3HBA在增强脂肪细胞的生理功能方面起着重要作用。
Ketone bodies, including 3HBA, are endogenous products of fatty acid oxidation, and Hmgcs2 is the first rate-limiting enzyme of ketogenesis. From database analysis and in vivo and in vitro experiments, we found that adipose tissue and adipocytes express Hmgcs2, and that adipocytes produce and secrete 3HBA. Treatment with 3HBA enhanced the gene expression levels of the antioxidative stress factors, PPARγ, and lipogenic factors in adipose tissue in vivo and in adipocytes in vitro, accompanied by reduced ROS levels. Knockdown of endogenous Hmgcs2 in adipocytes markedly decreased 3HBA levels in adipocytes and decreased the gene expression levels of the antioxidative stress factors, PPARγ, and lipogenic factors with increased ROS levels. Conversely, overexpression of Hmgcs2 in adipocytes increased 3HBA secretion from adipocytes and enhanced the gene expression levels of the antioxidative stress factors, PPARγ, and lipogenic factors. These results demonstrate that 3HBA plays significant roles in enhancing the physiological function of adipocytes.
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