Chronic inflammation aggravates metabolic disorders of hepatic fatty acids in high-fat diet-induced obese mice

• Published in: Scientific reports Vol. 5; no. 1; p. 10222
• Main Authors: Zhao, Lei, Zhong, Shan, Qu, Haiyang, Xie, Yunxia, Cao, Zhennan, Li, Qing, Yang, Ping, Varghese, Zac, Moorhead, John F., Chen, Yaxi, Ruan, Xiong Z.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 14.05.2015; Nature Publishing Group
• Subjects: 13/21; 13/51; 14/63; 38/77; 692/420/256/2515; 692/699/317; 82/1; 82/29; 82/51; Animals; Body mass; Body Mass Index; Casein; Caseins - administration & dosage; Caseins - pharmacology; Cells, Cultured; Cytokines; Cytokines - blood; Degeneration; Diet; Diet, High-Fat; Endoplasmic reticulum; Endoplasmic Reticulum Stress - physiology; Fatty acids; Fatty Acids - biosynthesis; Fatty liver; High fat diet; Humanities and Social Sciences; Hyperlipidemia; Inflammation; Inflammation - chemically induced; Inflammation - immunology; Injection; Lipid Metabolism; Liver - pathology; Liver diseases; Male; Metabolic disorders; Mice; Mice, Inbred C57BL; Mice, Obese; multidisciplinary; Non-alcoholic Fatty Liver Disease - pathology; Obesity; Obesity - metabolism; Oxidation; Oxidation-Reduction; Oxidative Stress; Rodents; Science; Steatosis
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep10222

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.