Long-term fatty liver-induced insulin resistance in orotic acid-induced nonalcoholic fatty liver rats

Author:

Han Xiuqing1,Liu Chunhua2,Xue Yong1,Wang Jingfeng1,Xue Changhu1,Yanagita Teruyoshi3,Gao Xiang14,Wang Yuming1

Affiliation:

1. College of Food Science and Engineering, Ocean University of China, Qingdao, China

2. Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China

3. Health and Nutrition Science, Nishi kyushu University, Kanzaki, Japan

4. Faculty of Medicine, Memorial University, Saint John's, Canada

Abstract

Abstract We investigated whether fatty liver preceded insulin resistance or vice versa using a long-term orotic acid (OA)-induced nonalcoholic fatty liver disease (NAFLD) model without the confounding effects of obesity and hyperlipidemia and explored the role of the liver in insulin resistance. Male Wistar rats were fed with or without OA supplementation for 30, 60, and 90 days. The NAFLD group showed increased liver lipid at 30, 60, and 90 days; glucose intolerance was noted at 60 and 90 days. Furthermore, partial liver proteins and gene expressions related to upstream signaling of insulin were decreased. However, the liver glycogen content was elevated, and gluconeogenesis genes expressions were obviously decreased at 90 days. The occurrence of fatty liver preceded insulin resistance in OA-induced NAFLD without the interference of obesity and hyperlipidemia, and hepatic insulin resistance may not play a conclusive role in insulin resistance in this model.

Funder

National Natural Science Foundation of China

Publisher

Oxford University Press (OUP)

Subject

Organic Chemistry,Molecular Biology,Applied Microbiology and Biotechnology,General Medicine,Biochemistry,Analytical Chemistry,Biotechnology

Reference36 articles.

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