Intrahepatic Diacylglycerol Content Is Associated With Hepatic Insulin Resistance in Obese Subjects

被引：156

作者：

Magkos, Faidon ^{[1
]}

Su, Xiong ^{[1
]}

Bradley, David ^{[1
]}

Fabbrini, Elisa ^{[1
,4
]}

Conte, Caterina ^{[1
,5
]}

Eagon, J. Christopher ^{[1
,2
]}

Varela, J. Esteban ^{[1
,2
]}

Brunt, Elizabeth M. ^{[1
,3
]}

Patterson, Bruce W. ^{[1
]}

Klein, Samuel ^{[1
]}

机构：

[1] Washington Univ, Sch Med, Ctr Human Nutr, St Louis, MO 63110 USA

[2] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA

[3] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA

[4] Inst Ricovero & Cura Carattere Sci San Raffaele, Dept Med Sci, Ctr Clin & Basic Res, Rome, Italy

[5] Sapienza Univ Rome, Dept Clin Med, Rome, Italy

来源：

GASTROENTEROLOGY | 2012年 / 142卷 / 07期

基金：

美国国家卫生研究院;

关键词：

Obesity; Lipid Intermediates; Lipid-Induced Insulin Resistance; NAFLD; LIVER; SUPPRESSION; STEATOSIS; MICE;

D O I：

10.1053/j.gastro.2012.03.003

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Data from studies in animal models indicate that certain lipid metabolites, particularly diacylglycerol, ceramide, and acylcarnitine, disrupt insulin action. We evaluated the relationship between the presence of these metabolites in the liver (assessed by mass spectrometry) and hepatic insulin sensitivity (assessed using a hyperinsulinemic-euglycemic clamp with stable isotope tracer infusion) in 16 obese adults (body mass index, 48 +/- 9 kg/m(2)). There was a negative correlation between insulin-mediated suppression of hepatic glucose production and intrahepatic diacylglycerol (r = -0.609; P = .012), but not with intrahepatic ceramide or acylcarnitine. These data indicate that intrahepatic diacylglycerol is an important mediator of hepatic insulin resistance in obese people with nonalcoholic fatty liver disease.

引用

页码：1444 / +

页数：5

共 25 条

[1] Dissociation Between Intrahepatic Triglyceride Content and Insulin Resistance in Familial Hypobetalipoproteinemia [J].

Amaro, Anastassia ;

Fabbrini, Elisa ;

Kars, Marleen ;

Yue, Pin ;

Schechtman, Kenneth ;

Schonfeld, Gustav ;

Klein, Samuel .

GASTROENTEROLOGY, 2010, 139 (01) :149-153

[2] Suppression of diacylglycerol acyltransferase-2 (DGAT2), but not DGAT1, with antisense oligonucleotides reverses diet-induced hepatic steatosis and insulin resistance [J].

Choi, Cheol Soo ;

Savage, David B. ;

Kulkarni, Ameya ;

Yu, Xing Xian ;

Liu, Zhen-Xiang ;

Morino, Katsutaro ;

Kim, Sheene ;

Distefano, Alberto ;

Samuel, Varman T. ;

Neschen, Susanne ;

Zhang, Dongyan ;

Wang, Amy ;

Zhang, Xian-Man ;

Kahn, Mario ;

Cline, Gary W. ;

Pandey, Sanjay K. ;

Geisler, John G. ;

Bhanot, Sanjay ;

Monia, Brett P. ;

Shulman, Gerald I. .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (31) :22678-22688

[3] Insulin resistance, lipotoxicity, type 2 diabetes and atherosclerosis: the missing links. The Claude Bernard Lecture 2009 [J].

DeFronzo, R. A. .

DIABETOLOGIA, 2010, 53 (07) :1270-1287

[4] Diacylglycerol-mediated insulin resistance [J].

Erion, Derek M. ;

Shulman, Gerald I. .

NATURE MEDICINE, 2010, 16 (04) :400-402

[5] Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity [J].

Fabbrini, Elisa ;

Magkos, Faidon ;

Mohammed, B. Selma ;

Pietka, Terri ;

Abumrad, Nada A. ;

Patterson, Bruce W. ;

Okunade, Adewole ;

Klein, Samuel .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (36) :15430-15435

[6] Apoptosis and insulin resistance in liver and peripheral tissues of morbidly obese patients is associated with different stages of non-alcoholic fatty liver disease [J].

Ferreira, D. M. S. ;

Castro, R. E. ;

Machado, M. V. ;

Evangelista, T. ;

Silvestre, A. ;

Costa, A. ;

Coutinho, J. ;

Carepa, F. ;

Cortez-Pinto, H. ;

Rodrigues, C. M. P. .

DIABETOLOGIA, 2011, 54 (07) :1788-1798

[7]

Frimel Tiffany N, 2007, J Cardiometab Syndr, V2, P136, DOI 10.1111/j.1559-4564.2007.07168.x

[8] Hepatic insulin resistance in mice with hepatic overexpression of diacylglycerol acyltransferase 2 [J].

Jornayvaz, Francois R. ;

Birkenfeld, Andreas L. ;

Jurczak, Michael J. ;

Kanda, Shoichi ;

Guigni, Blas A. ;

Jiang, Debbie C. ;

Zhang, Dongyan ;

Lee, Hui-Young ;

Samuel, Varman T. ;

Shulman, Gerald I. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2011, 108 (14) :5748-5752

[9] Clinical importance of obesity versus the metabolic syndrome in cardiovascular risk in women - A report from the Women's Ischemia Syndrome Evaluation (WISE) study [J].

Kip, KE ;

Marroquin, OC ;

Kelley, DE ;

Johnson, BD ;

Kelsey, SF ;

Shaw, LJ ;

Rogers, WJ ;

Reis, SE .

CIRCULATION, 2004, 109 (06) :706-713

[10] Design and validation of a histological scoring system for nonalcoholic fatty liver disease [J].

Kleiner, DE ;

Brunt, EM ;

Van Natta, M ;

Behling, C ;

Contos, MJ ;

Cummings, OW ;

Ferrell, LD ;

Liu, YC ;

Torbenson, MS ;

Unalp-Arida, A ;

Yeh, M ;

McCullough, AJ ;

Sanyal, AJ .

HEPATOLOGY, 2005, 41 (06) :1313-1321

← 1 2 3 →