The bile acid induced hepatokine orosomucoid suppresses adipocyte differentiation.
The bile acid induced hepatokine orosomucoid suppresses adipocyte differentiation.
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DOI：
10.1016/j.bbrc.2020.10.086
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发表时间：
2021-01-01
影响因子：
3.1
通讯作者：
Kim KH
中科院分区：
文献类型：
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作者：
Lee SH;Choi JM;Jung SY;Cox AR;Hartig SM;Moore DD;Kim KH
胆汁酸最近已成为关键的代谢激素，对多种代谢性疾病具有有益的影响。我们先前发现，肝脏胆汁酸超负荷通过调节脂肪组织中的葡萄糖和脂肪酸代谢来发挥减肥作用。然而，解释血清胆汁酸升高有益效果的详细机制仍不清楚。在这里，蛋白质组学研究发现了一种新的肝素，OroSomucid(ORM)，它控制着肝脏-脂肪组织的串扰。遗传性和膳食胆汁酸超负荷均可高度诱发肝脏OMs。为了研究ORM的直接代谢作用，将纯化的ORM蛋白应用于3T3-L1细胞和小鼠基质血管成纤维细胞的成脂分化过程中。ORM抑制脂肪细胞分化，强烈抑制成脂转录因子C/EBPβ、KLF5、C/EBPα和PPARγ的基因表达。综上所述，我们的数据清楚地表明，胆汁酸诱导的肝脏ORM分泌阻止了脂肪细胞的分化，这可能与胆汁酸的抗肥胖作用有关。
Bile acids have recently emerged as key metabolic hormones with beneficial impacts in multiple metabolic diseases. We previously discovered that hepatic bile acid overload distally modulates glucose and fatty acid metabolism in adipose tissues to exert anti-obesity effects. However, the detailed mechanisms that explain the salutary effects of serum bile acid elevation remain unclear. Here, proteomic profiling identified a new hepatokine, Orosomucoid (ORM) that governs liver-adipose tissue crosstalk. Hepatic ORMs were highly induced by both genetic and dietary bile acid overload. To address the direct metabolic effects of ORM, purified ORM proteins were administered during adipogenic differentiation of 3T3-L1 cells and mouse stromal vascular fibroblasts. ORM suppressed adipocyte differentiation and strongly inhibited gene expression of adipogenic transcription factors such as C/EBPβ, KLF5, C/EBPα, and PPARγ. Taken together, our data clearly suggest that bile acid-induced ORM secretion from the liver blocks adipocyte differentiation, potentially linked to anti-obesity effect of bile acids.
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