| Literature DB >> 19254570 |
Yoshio Nagai1, Shin Yonemitsu, Derek M Erion, Takanori Iwasaki, Romana Stark, Dirk Weismann, Jianying Dong, Dongyan Zhang, Michael J Jurczak, Michael G Löffler, James Cresswell, Xing Xian Yu, Susan F Murray, Sanjay Bhanot, Brett P Monia, Jonathan S Bogan, Varman Samuel, Gerald I Shulman.
Abstract
Peroxisome proliferator-activated receptor gamma coactivator-1 beta (PGC-1beta) is known to be a transcriptional coactivator for SREBP-1, the master regulator of hepatic lipogenesis. Here, we evaluated the role of PGC-1beta in the pathogenesis of fructose-induced insulin resistance by using an antisense oligonucletoide (ASO) to knockdown PGC-1beta in liver and adipose tissue. PGC-1beta ASO improved the metabolic phenotype induced by fructose feeding by reducing expression of SREBP-1 and downstream lipogenic genes in liver. PGC-1beta ASO also reversed hepatic insulin resistance induced by fructose in both basal and insulin-stimulated states. Furthermore, PGC-1beta ASO increased insulin-stimulated whole-body glucose disposal due to a threefold increase in glucose uptake in white adipose tissue. These data support an important role for PGC-1beta in the pathogenesis of fructose-induced insulin resistance and suggest that PGC-1beta inhibition may be a therapeutic target for treatment of NAFLD, hypertriglyceridemia, and insulin resistance associated with increased de novo lipogenesis.Entities:
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Year: 2009 PMID： 19254570 PMCID： PMC3131094 DOI： 10.1016/j.cmet.2009.01.011
Source DB: PubMed Journal: Cell Metab ISSN： 1550-4131 Impact factor: 27.287