1. Chronic inflammation aggravates metabolic disorders of hepatic fatty acids in high-fat diet-induced obese mice.
- Author
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Zhao, Lei, Zhong, Shan, Qu, Haiyang, Xie, Yunxia, Cao, Zhennan, Li, Qing, Yang, Ping, Varghese, Zac, Moorhead, John F., Chen, Yaxi, and Ruan, Xiong Z.
- Subjects
CHRONICALLY ill ,CHRONIC disease treatment ,LIVER diseases ,BODY mass index ,FATTY degeneration - Abstract
The prevalence of nonalcoholic fatty liver disease (NAFLD) increases with increasing body mass index (BMI). However, approximately 40-50% of obese adults do not develop hepatic steatosis. The level of inflammatory biomarkers is higher in obese subjects with NAFLD compared to BMI-matched subjects without hepatic steatosis. We used a casein injection in high-fat diet (HFD)-fed C57BL/6J mice to induce inflammatory stress. Although mice on a HFD exhibited apparent phenotypes of obesity and hyperlipidemia regardless of exposure to casein injection, only the HFD+Casein mice showed increased hepatic vacuolar degeneration accompanied with elevated inflammatory cytokines in the liver and serum, compared to mice on a normal chow diet. The expression of genes related to hepatic fatty acid synthesis and oxidation were upregulated in the HFD-only mice. The casein injection further increased baseline levels of lipogenic genes and decreased the levels of oxidative genes in HFD-only mice. Inflammatory stress induced both oxidative stress and endoplasmic reticulum stress in HFD-fed mice livers. We conclude that chronic inflammation precedes hepatic steatosis by disrupting the balance between fatty acid synthesis and oxidation in the livers of HFD-fed obese mice. This mechanism may operate in obese individuals with chronic inflammation, thus making them more prone to NAFLD. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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