The Role of Peroxisome Proliferator-Activated Receptor γ Coactivator-1 β in the Pathogenesis of Fructose-Induced Insulin Resistance

被引：173

作者：

Nagai, Yoshio ^{[1
,4
]}

Yonemitsu, Shin ^{[1
,4
]}

Erion, Derek M. ^{[1
,2
,4
]}

Iwasaki, Takanori ^{[1
]}

Stark, Romana ^{[1
]}

Weismann, Dirk ^{[1
]}

Dong, Jianying ^{[1
]}

Zhang, Dongyan ^{[1
,4
]}

Jurczak, Michael J. ^{[1
,4
]}

Loeffler, Michael G. ^{[1
]}

Cresswell, James ^{[1
]}

Yu, Xing Xian ^{[5
]}

Murrays, Susan F. ^{[5
]}

Bhanot, Sanjay ^{[5
]}

Monia, Brett P. ^{[5
]}

Bogan, Jonathan S. ^{[1
,3
]}

Samuel, Varman ^{[1
]}

Shulman, Gerald I. ^{[1
,2
,4
]}

机构：

[1] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06536 USA

[2] Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06536 USA

[3] Yale Univ, Sch Med, Dept Cell Biol, New Haven, CT 06536 USA

[4] Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06536 USA

[5] ISIS Pharmaceut, Carlsbad, CA 92008 USA

来源：

CELL METABOLISM | 2009年 / 9卷 / 03期

关键词：

ELEMENT-BINDING PROTEIN; FATTY LIVER-DISEASE; MITOCHONDRIAL DYSFUNCTION; GLUCOSE-METABOLISM; SREBP-1C PROMOTER; HEPATIC STEATOSIS; KINASE-C; PGC-1-BETA; EXPRESSION; MUSCLE;

D O I：

10.1016/j.cmet.2009.01.011

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Peroxisome proliferator-activated receptor gamma coactivator-1 beta (PGC-1 beta) is known to be a transcriptional coactivator for SREBP-1, the master regulator of hepatic lipogenesis. Here, we evaluated the role of PGC-1 beta in the pathogenesis of fructose-induced insulin resistance by using an antisense oligonucletoide (ASO) to knockdown PGC-1 beta in liver and adipose tissue. PGC-1 beta ASO improved the metabolic phenotype induced by fructose feeding by reducing expression of SREBP-1 and downstream lipogenic genes in liver. PGC-1 beta ASO also reversed hepatic insulin resistance induced by fructose in both basal and insulin-stimulated states. Furthermore, PGC-1 beta 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-1 beta in the pathogenesis of fructose-induced insulin resistance and suggest that PGC-1 0 inhibition may be a therapeutic target for treatment of NAFLD, hypertriglyceridemia, and insulin resistance associated with increased de novo lipogenesis.

引用

页码：252 / 264

页数：13

共 38 条

[1] Fructose, insulin resistance, and metabolic dyslipidemia [J].

Basciano H. ;

Federico L. ;

Adeli K. .

Nutrition & Metabolism, 2 (1)

[2] Quantitative analysis of total mitochondrial DNA: Competitive polymerase chain reaction versus real-time polymerase chain reaction [J].

Bhat, HK ;

Epelboym, I .

JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, 2004, 18 (04) :180-186

[3]

BLIGH EG, 1959, CAN J BIOCHEM PHYS, V37, P911

[4] Insulin activates the rat sterol-regulatory-element-binding protein 1c (SREBP-1c) promoter through the combinatorial actions of SREBP, LXR, Sp-1 and NF-Y cis-acting elements [J].

Cagen, LM ;

Deng, X ;

Wilcox, HG ;

Park, EA ;

Raghow, R ;

Elam, MB .

BIOCHEMICAL JOURNAL, 2005, 385 :207-216

[5] Dietary carbohydrates and insulin sensitivity: A review of the evidence and clinical implications [J].

Daly, ME ;

Vale, C ;

Walker, M ;

Alberti, KGMM ;

Mathers, JC .

AMERICAN JOURNAL OF CLINICAL NUTRITION, 1997, 66 (05) :1072-1085

[6] Expression of the rat sterol regulatory element-binding protein-1c gene in response to insulin is mediated by increased transactivating capacity of specificity protein 1 (Sp1) [J].

Deng, Xiong ;

Yellaturu, Chandrahasa ;

Cagen, Lauren ;

Wilcox, Henry G. ;

Park, Edwards A. ;

Raghow, Rajendra ;

Elam, Marshall B. .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (24) :17517-17529

[7] Insulin activates human sterol-regulatory-element-binding protein-1c (SREBP-1c) promoter through SRE motifs [J].

Dif, Nicolas ;

Euthine, Vanessa ;

Gonnet, Estelle ;

Laville, Martine ;

Vidal, Hubert ;

Lefai, Etienne .

BIOCHEMICAL JOURNAL, 2006, 400 :179-188

[8] Fructose, weight gain, and the insulin resistance syndrome [J].

Elliott, SS ;

Keim, NL ;

Stern, JS ;

Teff, K ;

Havel, PJ .

AMERICAN JOURNAL OF CLINICAL NUTRITION, 2002, 76 (05) :911-922

[9] Regulation of SREBP-1 expression and transcriptional action on HKII and FAS genes during fasting and refeeding in rat tissues [J].

Gosmain, Y ;

Dif, N ;

Berbe, V ;

Loizon, E ;

Rieusset, J ;

Vidal, H ;

Lefai, E .

JOURNAL OF LIPID RESEARCH, 2005, 46 (04) :697-705

[10]

Havel PJ, 2005, NUTR REV, V63, P133, DOI [10.1301/nr.2005.may.133-157, 10.1111/j.1753-4887.2005.tb00132.x]

← 1 2 3 4 →