PPARr in the endothelium regulates metabolic responses to high-fat diet in mice (J Clin Invest, 2009, 119:110-124)

報告日期: 2009/05/26
報告時間: 17:05/17:55
報告學生: 劉雅惠
講評老師: 陳昌熙
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/980526-3.pdf

PPARg in the endothelium regulates metabolic

responses to high-fat diet in mice

J Clin Invest. 2009; 119(1):110-24

Speaker: 劉雅惠

Commentator: 陳昌熙 老師

Time: 2009/05/26 17:10-18:00

Place: Room 602

 

Abnormal vasomotor function is thought to be a key factor causing endothelial dysfunction. However, in the disease of insulin resistance and diabetes, these metabolic abnormalities are usually accompanied by endothelial dysfunction via unclear mechanisms. PPARg is a ligand-activated transcriptional factor regulating energy balance, but the specific role of endothelial PPARg in metabolic function still needs to be identified. The authors utilized Tie2Cre-mediated PPARg deficient mice, which exhibited defective PPARg in the endothelium and bone marrow (gEC/BM-KO), fed with high-fat diet to characterize the metabolic function. gEC/BM-KO mice have decreased white adipose tissue mass and adipocyte size after high-fat diet feeding. Although serum FFA and TG levels were increased in high-fat-diet fed gECBM-KO mice, TG accumulation in skeletal muscle was decreased as a contributor to the increased insulin sensitivity. BM transplantation showed that PPARg deficiency in the endothelial cell inhibited adipose tissue growth, increased FFA and TG levels, and improved insulin sensitivity, despite of PPARg expression in the BM. Moreover, PPARg agonist rosiglitazone failed to decrease FFA and TG levels and increased adipogenesis in mice with endothelial PPARg deficiency. The elevated serum FFA and TG levels in gEC/BM-KO mice were found to promote VLDL production and inhibit LPL activity. In summary, these data indicated that endothelial PPARg regulates previously unrecognized metabolic functions in insulin resistance and diabetes.

 

Reference:

1.   J Am Soc Nephrol 2004, 15:1983–1992. Endothelial Dysfunction

2.   Cell Research 2007, 17:486-511. Fat poetry: a kingdom for PPARγ