Abnormal lipid and glucose metabolism in obesity: Implications for nonalcoholic fatty liver disease

被引:252
作者
Parekh, Samir [1 ]
Anania, Frank A. [1 ]
机构
[1] Emory Univ, Sch Med, Dept Med, Div Digest Dis, Atlanta, GA 30322 USA
关键词
D O I
10.1053/j.gastro.2007.03.055
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Nonalcoholic fatty liver disease represents a spectrum of histopathologic abnormalities, the prevalence of which may be as high as 24% of the population of the United States. Nonalcoholic fatty liver disease will play a major role in the science and practice of gastroenterology in the near future. The fundamental derangement in nonalcoholic fatty liver disease is insulin resistance, a key component of the metabolic syndrome, which includes type 2 diabetes mellitus, hypertriglyceridemia, essential hypertension, low circulating high-density lipoprotein, and obesity. The natural,history of fatty liver disease is not always benign, and causality for cirrhosis and chronic liver disease is well-founded in the literature. Treatment strategies are limited and, at present, are primarily focused on weight loss and use of insulin sensitizing agents, including the thiazolidenediones. Recent data clearly implicate hepatic insulin resistance as a culprit in accumulation of free fatty acids as triglycerides in hepatocytes. Hepatic insulin resistance is clearly exacerbated by systemic insulin resistance and impaired handling by skeletal muscle and adipose tissue of both glucose and free fatty acids. The key consequence of hepatic insulin resistance, impaired hepatocyte insulin signal transduction, results in adverse cellular and molecular changes exacerbating hepatocyte triglyceride storage. Cytokines secreted by white adipose tissue, adipokines, have emerged as key players in glucose and fat metabolism previously thought controlled largely by insulin. Modulation of adipokines may aid in further understanding of the pathophysiology and treatment of nonalcoholic fatty liver disease.
引用
收藏
页码:2191 / 2207
页数:17
相关论文
共 162 条
[71]   Tissue-specific overexpression of lipoprotein lipase causes tissue-specific insulin resistance [J].
Kim, JK ;
Fillmore, JJ ;
Chen, Y ;
Yu, CL ;
Moore, IK ;
Pypaert, M ;
Lutz, EP ;
Kako, Y ;
Velez-Carrasco, W ;
Goldberg, IJ ;
Breslow, JL ;
Shulman, GI .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (13) :7522-7527
[72]   Primacy of hepatic insulin resistance in the development of the metabolic syndrome induced by an isocaloric moderate-fat diet in the dog [J].
Kim, SP ;
Ellmerer, M ;
Van Citters, GW ;
Bergman, RN .
DIABETES, 2003, 52 (10) :2453-2460
[73]   In vivo administration of leptin activates signal transduction directly in insulin-sensitive tissues:: Overlapping but distinct pathways from insulin [J].
Kim, YB ;
Uotani, S ;
Pierrez, DD ;
Flier, JS ;
Kahn, BB .
ENDOCRINOLOGY, 2000, 141 (07) :2328-2339
[74]   DEVELOPMENT OF MUSCLE INSULIN RESISTANCE AFTER LIVER INSULIN RESISTANCE IN HIGH-FAT FED RATS [J].
KRAEGEN, EW ;
CLARK, PW ;
JENKINS, AB ;
DALEY, EA ;
CHISHOLM, DJ ;
STORLIEN, LH .
DIABETES, 1991, 40 (11) :1397-1403
[75]   NONALCOHOLIC STEATOHEPATITIS - A STUDY OF 49 PATIENTS [J].
LEE, RG .
HUMAN PATHOLOGY, 1989, 20 (06) :594-598
[76]   Effects of obesity surgery on the metabolic syndrome [J].
Lee, WJ ;
Huang, MT ;
Wang, W ;
Lin, CM ;
Chen, TC ;
Lai, IR .
ARCHIVES OF SURGERY, 2004, 139 (10) :1088-1092
[77]   EFFECTS OF ACUTE HYPERINSULINEMIA ON VLDL TRIGLYCERIDE AND VLDL APO-B PRODUCTION IN NORMAL-WEIGHT AND OBESE INDIVIDUALS [J].
LEWIS, GF ;
UFFELMAN, KD ;
SZETO, LW ;
STEINER, G .
DIABETES, 1993, 42 (06) :833-842
[78]   Metformin reverses fatty liver disease in obese, leptin-deficient mice [J].
Lin, HZ ;
Yang, SQ ;
Chuckaree, C ;
Kuhajda, F ;
Ronnet, G ;
Diehl, AM .
NATURE MEDICINE, 2000, 6 (09) :998-1003
[79]  
LUDWIG J, 1980, MAYO CLIN PROC, V55, P434
[80]   Liver abnormalities in severely obese subjects:: Effect of drastic weight loss after gastroplasty [J].
Luyckx, FH ;
Desaive, C ;
Thiry, A ;
Dewé, W ;
Scheen, AJ ;
Gielen, JE ;
Lefèbvre, PJ .
INTERNATIONAL JOURNAL OF OBESITY, 1998, 22 (03) :222-226