title: Chronic inflammation aggravates metabolic disorders of hepatic fatty acids in high-fat diet-induced obese mice.
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.
authors.affiliation: Centre for Lipid Research, &Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Centre for Lipid Research, &Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Zhong
authors.affiliation: Centre for Lipid Research, &Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
authors.forename: Haiyang
authors.initials: H
authors.lastname: Qu
authors.affiliation: Centre for Lipid Research, &Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
authors.forename: Yunxia
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Centre for Lipid Research, &Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
authors.forename: Zhennan
authors.initials: Z
authors.lastname: Cao
authors.affiliation: Centre for Lipid Research, &Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.affiliation: Centre for Lipid Research, &Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
authors.affiliation: John Moorhead Research Laboratory, Centre for Nephrology, University College London Medical School, Royal Free Campus, University College London, London, UK.
authors.forename: Zac
authors.initials: Z
authors.lastname: Varghese
authors.affiliation: John Moorhead Research Laboratory, Centre for Nephrology, University College London Medical School, Royal Free Campus, University College London, London, UK.
authors.forename: John F
authors.initials: JF
authors.lastname: Moorhead
authors.affiliation: Centre for Lipid Research, &Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
authors.forename: Yaxi
authors.initials: Y
authors.lastname: Chen
authors.affiliation: 1] Centre for Lipid Research, &Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China [2] John Moorhead Research Laboratory, Centre for Nephrology, University College London Medical School, Royal Free Campus, University College London, London, UK.
authors.forename: Xiong Z
authors.initials: XZ
authors.lastname: Ruan
mesh_terms: D000818:Animals; D015992:Body Mass Index; D002364:Caseins / Q000008:administration & dosage / Q000494:pharmacology*; D002478:Cells, Cultured; D016207:Cytokines / Q000097:blood; D059305:Diet, High-Fat; D059865:Endoplasmic Reticulum Stress / Q000502:physiology; D005227:Fatty Acids / Q000096:biosynthesis*; D007249:Inflammation / Q000139:chemically induced* / Q000276:immunology; D050356:Lipid Metabolism; D008099:Liver / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D065626:Non-alcoholic Fatty Liver Disease / Q000473:pathology*; D009765:Obesity / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress
chemical_list: D002364:Caseins; D016207:Cytokines; D005227:Fatty Acids