生长激素抑制牛皮下脂肪细胞的脂肪生成分化并诱导其褐变。
Growth hormone inhibits adipogenic differentiation and induces browning in bovine subcutaneous adipocytes.
作者信息
Li Tingting, Bai Hui, Fang Haoyuan, Yang Liang, Yan Peishi
机构信息
College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China.
College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China.
出版信息
Growth Horm IGF Res. 2022 Oct;66:101498. doi: 10.1016/j.ghir.2022.101498. Epub 2022 Aug 18.
OBJECTIVE
It is well established that growth hormone (GH) has the ability to stimulate lipolysis. The effects of GH on adipocyte differentiation and browning have not been clearly described. Therefore, the present study aimed to elucidate the role of GH in the differentiation and browning of bovine subcutaneous adipocytes as well as its underlying molecular mechanisms.
METHODS
We first treated bovine subcutaneous preadipocytes with different concentrations (0, 10, 100, and 500 ng/mL) of GH for 8 days and measured lipid accumulation and gene expression. Afterward, we treated preadipocytes and mature adipocytes with 500 ng/mL GH and determined differentiation and browning-related indicators. Finally, we investigated the expression of STAT5B in both preadipocytes and mature adipocytes after GH treatment.
RESULTS
We demonstrated that GH inhibited lipid accumulation and decreased the expression levels of adipogenic key genes (SCD1, SREBP1, PPARγ, and CEBPα) during adipocyte differentiation. Moreover, we observed that the inhibitory effect of GH on the early stage of adipocyte differentiation (0-2 days) was stronger than that on the later stage of adipocyte differentiation (2-8 days). We also found that GH promoted the expression levels of browning-related genes such as uncoupling protein 1 (UCP1) in mature adipocytes. Concurrently, GH promoted mitochondrial biogenesis and increased the expression levels of mitochondrial biogenesis-related genes. In addition, GH promoted phosphorylation of signal transducers and activator of transcription 5 b (STAT5B) and contributed to translocation of STAT5B to nucleus. After blocking the expression of STAT5B protein, GH weakened the inhibition of adipogenic key genes and reduced the promotion of browning-related genes in bovine subcutaneous adipocytes.
CONCLUSIONS
GH can inhibit adipocyte differentiation and promote adipocyte browning by regulating STAT5B in bovine subcutaneous adipocytes.
目的
生长激素（GH）具有刺激脂肪分解的能力，这一点已得到充分证实。然而，GH对脂肪细胞分化和褐变的影响尚未得到明确描述。因此，本研究旨在阐明GH在牛皮下脂肪细胞分化和褐变中的作用及其潜在分子机制。
方法
我们首先用不同浓度（0、10、100和500 ng/mL）的GH处理牛皮下前脂肪细胞8天，并测量脂质积累和基因表达。之后，我们用500 ng/mL GH处理前脂肪细胞和成熟脂肪细胞，并测定分化和褐变相关指标。最后，我们研究了GH处理后前脂肪细胞和成熟脂肪细胞中信号转导子和转录激活子5B（STAT5B）的表达。
结果
我们证明，GH在脂肪细胞分化过程中抑制脂质积累，并降低脂肪生成关键基因（SCD1、SREBP1、PPARγ和CEBPα）的表达水平。此外，我们观察到，GH对脂肪细胞分化早期（0-2天）的抑制作用强于对脂肪细胞分化后期（2-8天）的抑制作用。我们还发现，GH促进成熟脂肪细胞中解偶联蛋白1（UCP1）等褐变相关基因的表达水平。同时，GH促进线粒体生物发生，并增加线粒体生物发生相关基因的表达水平。此外，GH促进信号转导子和转录激活子5B（STAT5B）的磷酸化，并促使STAT5B转位至细胞核。在阻断STAT5B蛋白表达后，GH减弱了对牛皮下脂肪细胞脂肪生成关键基因的抑制作用，并降低了对褐变相关基因的促进作用。
结论
在牛皮下脂肪细胞中GH可通过调节STAT5B抑制脂肪细胞分化并促进脂肪细胞褐变。
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