Inflammatory stress exacerbates ectopic lipid deposition in C57BL/6J mice

• Published in: Lipids in health and disease Vol. 10; no. 1; p. 110
• Main Authors: Mei, Mei, Zhao, Lei, Li, Qing, Chen, Yaxi, Huang, Ailong, Varghese, Zac, Moorhead, John F, Zhang, Suhua, Powis, Stephen H, Li, Qifu, Ruan, Xiong Z
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 30.06.2011; BioMed Central; BMC
• Subjects: acetyl CoA carboxylase; Acetyl-CoA Carboxylase - genetics; Acetyl-CoA Carboxylase - metabolism; Adipose Tissue, White - enzymology; Adipose Tissue, White - metabolism; Adipose Tissue, White - pathology; Adipose tissues; adipose triglyceride lipase; Animals; Blood; Blood Glucose; Caseins; fatty acid synthase; Fatty Acid Synthase, Type I - genetics; Fatty Acid Synthase, Type I - metabolism; Fatty Acids, Nonesterified - blood; Gene Expression; Inflammation; Inflammation - chemically induced; Insulin - blood; Insulin Resistance; Interleukin-6 - blood; Lipid Metabolism; Lipolysis; Liver - enzymology; Liver - metabolism; Liver - pathology; Medical examination; Mice; Mice, Inbred C57BL; Muscle, Skeletal - enzymology; Muscle, Skeletal - metabolism; Muscle, Skeletal - pathology; Physiological aspects; Risk factors; Serum Amyloid A Protein - metabolism; Sterol Regulatory Element Binding Protein 1 - genetics; Sterol Regulatory Element Binding Protein 1 - metabolism; sterol regulatory element binding protein1; Stress, Physiological; United Kingdom; China
• ISSN: 1476-511X; 1476-511X
• DOI: 10.1186/1476-511X-10-110

Chronic systemic inflammation and abnormal free fatty acid metabolism are closely related to ectopic lipid deposition. In this study, we investigate if inflammation tissue-specifically disrupts lipogenesis and lipolysis in nonadipose tissues and adipose tissue, resulting in ectopic lipid deposition in C57BL/6J mice. We used casein injection in C57BL/6J mice to induce a chronic systemic inflammatory stress in vivo. Serum was analyzed for free fatty acid and cytokines. Insulin sensitivities were evaluated by glucose and insulin tolerance tests. Liver, muscle, adipose tissues were taken for lipid analysis. Real-time polymerase chain reaction and western blotting were used to examine the gene and protein expression of molecules involved in adipogenesis and lipolysis in tissues. Casein injection elevated serum levels of IL-6 and SAA in mice, which are associated with increased lipid accumulation in liver and muscle, suggesting that chronic systemic inflammation induces ectopic lipid deposition in nonadipose tissues. The inflammatory stress upregulated mRNA and protein expression of sterol regulatory element binding protein 1, fatty acid synthase, and acetyl CoA carboxylase alpha, while inhibited these molecules expression in adipose. Interestingly, in the same experimental setting, inflammation increased triglyceride lipase and hormone-sensitive lipase expression in white adipose tissue. Inflammation also induced insulin resistance and increased serum free fatty acid levels in C57BL/6J mice. Chronic systemic inflammation increased lipogenesis in nonadipose tissues and lipolysis in white adipose tissue, resulting in ectopic lipid deposition in nonadipose tissues. This disturbed free fatty acid homeostasis and caused insulin resistance in C57BL/6J mice.