The role of peroxisome proliferator-activated receptor gamma coactivator-1 beta in the pathogenesis of fructose-induced insulin resistance.

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 Metab

journal_title

Cell metabolism

authors

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 GI

doi

10.1016/j.cmet.2009.01.011

subject

Has Abstract

pub_date

2009-03-01 00:00:00

pages

252-64

issue

3

eissn

1550-4131

issn

1932-7420

pii

S1550-4131(09)00036-9

journal_volume

9

pub_type

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