脂肪生成
脂肪组织
白色脂肪组织
医学
内科学
内分泌学
生物
生物信息学
作者
Alexander Hu,Wei Li,Cao-Thang Dinh,Yongzhao Zhang,Jamie Katy Hu,Stefano G. Daniele,Xiaoli Hou,Zixuan Yang,John M. Asara,Guo‐fu Hu,Stephen R. Farmer,Miaofen G. Hu
标识
DOI:10.1038/s41467-024-45294-z
摘要
Abstract Increased de novo lipogenesis (DNL) in white adipose tissue is associated with insulin sensitivity. Under both Normal-Chow-Diet and High-Fat-Diet, mice expressing a kinase inactive Cyclin-dependent kinase 6 ( Cdk6 ) allele ( K43M ) display an increase in DNL in visceral white adipose tissues (VAT) as compared to wild type mice ( WT ), accompanied by markedly increased lipogenic transcriptional factor Carbohydrate-responsive element-binding proteins (CHREBP) and lipogenic enzymes in VAT but not in the liver. Treatment of WT mice under HFD with a CDK6 inhibitor recapitulates the phenotypes observed in K43M mice. Mechanistically, CDK6 phosphorylates AMP-activated protein kinase, leading to phosphorylation and inactivation of acetyl-CoA carboxylase, a key enzyme in DNL. CDK6 also phosphorylates CHREBP thus preventing its entry into the nucleus. Ablation of runt related transcription factor 1 in K43M mature adipocytes reverses most of the phenotypes observed in K43M mice. These results demonstrate a role of CDK6 in DNL and a strategy to alleviate metabolic syndromes.
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