Nature子刊：营养过剩促进脂肪细胞衰老，加剧代谢疾病 | 热心肠日报
Age-associated telomere attrition in adipocyte progenitors predisposes to metabolic disease
年龄相关的脂肪祖细胞端粒磨损易诱发代谢性疾病
10.1038/s42255-020-00320-4
12-14, Article
Abstract & Authors:展开
Abstract:收起
White and beige adipocytes in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) are maintained by proliferation and differentiation of adipose progenitor cells (APCs). Here we use mice with tissue-specific telomerase reverse transcriptase (TERT) gene knockout (KO), which undergo premature telomere shortening and proliferative senescence in APCs, to investigate the effect of over-nutrition on APC exhaustion and metabolic dysfunction. We find that TERT KO in the Pdgfra+ cell lineage results in adipocyte hypertrophy, inflammation and fibrosis in SAT, while TERT KO in the Pdgfrb+ lineage leads to adipocyte hypertrophy in both SAT and VAT. Systemic insulin resistance is observed in both KO models and is aggravated by a high-fat diet. Analysis of human biopsies demonstrates that telomere shortening in SAT is associated with metabolic disease progression after bariatric surgery. Our data indicate that over-nutrition can promote APC senescence and provide a mechanistic link between ageing, obesity and diabetes.
First Authors:
Zhanguo Gao
Correspondence Authors:
Mikhail G Kolonin
All Authors:
Zhanguo Gao,Alexes C Daquinag,Cale Fussell,Zhongming Zhao,Yulin Dai,Angielyn Rivera,Brad E Snyder,Kristin L Eckel-Mahan,Mikhail G Kolonin