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.
journal_name
Cell Metabjournal_title
Cell metabolismauthors
Nagai Y,Yonemitsu S,Erion DM,Iwasaki T,Stark R,Weismann D,Dong J,Zhang D,Jurczak MJ,Löffler MG,Cresswell J,Yu XX,Murray SF,Bhanot S,Monia BP,Bogan JS,Samuel V,Shulman GIdoi
10.1016/j.cmet.2009.01.011subject
Has Abstractpub_date
2009-03-01 00:00:00pages
252-64issue
3eissn
1550-4131issn
1932-7420pii
S1550-4131(09)00036-9journal_volume
9pub_type
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