A model of insulin resistance and nonalcoholic steatohepatitis in rats -: Role of peroxisome proliferator-activated receptor-α and n-3 polyunsaturated fatty acid treatment on liver injury

被引：205

作者：

Svegliati-Baroni, Gianluca

Candelaresi, Cinzia

Saccomanno, Stefania

Ferretti, Gianna

Bachetti, Tiziana

Marzioni, Marco

De Minicis, Sarnuele

Nobili, Liliana

Salzano, Renata

Omenetti, Alessia

Pacetti, Deborah

Sigmund, Soeren

Benedetti, Antonio

Casini, Alessandro

机构：

[1] Univ Politecn Marche, Gastroenterol Clin, Dept Gastroenterol, I-60020 Ancona, Italy

[2] Univ Politecn Marche, Inst Biochem, Ancona, Italy

[3] Univ Politecn Marche, Dept Food Sci, Ancona, Italy

[4] Nerviano Med Sci, Clin Pathol Lab, Preclin Dev, Nerviano, Italy

[5] Univ Florence, Dept Clin Pathophysiol, Nutr Ctr, Florence, Italy

[6] Univ Florence, Dept Clin Pathophysiol, GI Unit, Florence, Italy

[7] Columbia Univ, Coll Phys & Surg, Med Ctr, Dept Med, New York, NY USA

[8] Multidisciplinary Ctr Res Food Sci, Florence, Italy

来源：

AMERICAN JOURNAL OF PATHOLOGY | 2006年 / 169卷 / 03期

关键词：

D O I：

10.2353/ajpath.2006.050953

中图分类号：

R36 [病理学];

学科分类号：

100104 ;

摘要：

Insulin resistance induces nonalcoholic fatty liver disease and nonalcoholic steatoliepatitis (NASH). We used a high-fat, high-calorie solid diet (HID) to create a model of insulin resistance and NASH in nongenetically modified rats and to study the relationship between visceral adipose tissue and liver. Obesity and insulin resistance occurred in HID rats, accompanied by a progressive increase in visceral adipose tissue tumor necrosis factor (TNF)-alpha mRNA and in circulating free fatty acids. HFD also decreased adiponectin mRNA and peroxisome proliferator-activated receptor (PPAR)-alpha expression in the visceral adipose tissue and the liver, respectively, and induced hepatic insulin resistance through TNF-alpha-mediated c-Jun N-terminal kinase (JNK)-dependent insulin receptor sub-strate-1(Ser307) phosphorylation. These modifications lead to hepatic steatosis accompanied by oxidative stress phenomena, necroinflammation, and hepatocyte apoptosis at 4 weeks and by pericentral fibrosis

引用

页码：846 / 860

页数：15

共 58 条

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