Cathelicidin suppresses lipid accumulation and hepatic steatosis by inhibition of the CD36 receptor

• Published in: International Journal of Obesity 2016-09, Vol.40 (9), p.1424-1434
• Main Authors: Hoang-Yen Tran, D, Hoang-Ngoc Tran, D, Mattai, S A, Sallam, T, Ortiz, C, Lee, E C, Robbins, L, Ho, S, Lee, J E, Fisseha, E, Shieh, C, Sideri, A, Shih, D Q, Fleshner, P, McGovern, D P B, Vu, M, Hing, T C, Bakirtzi, K, Cheng, M, Su, B, Law, I, Karagiannides, I, Targan, S R, Gallo, R L, Li, Z, Koon, H W
• Format: Article
• Language: English
• Subjects: 13/109; 38/77; 3T3-L1 Cells; 631/443/319/1642/393; 631/443/319/2723; 631/45/612/1237; 631/80/86; 64/60; 692/4020/4021/1607; 96/95; Accumulation; Adipocytes; Adipocytes - cytology; Adipocytes - drug effects; Adipocytes - metabolism; Animals; Antiinfectives and antibacterials; Antimicrobial Cationic Peptides - pharmacology; Antimicrobial peptides; Body fat; Body mass index; Body size; Cathelicidins; CD36 antigen; CD36 Antigens - biosynthesis; CD36 Antigens - genetics; Cell Differentiation - drug effects; Diabetes; Diabetes mellitus; Diabetes Mellitus, Experimental; Diet; Diet, High-Fat - adverse effects; Disease Models, Animal; Enzyme-linked immunosorbent assay; Epidemiology; Fatty acids; Fatty liver; Fatty Liver - complications; Fatty Liver - drug therapy; Fatty Liver - metabolism; Fatty Liver - prevention & control; Gene Expression Regulation - drug effects; Health aspects; Health Promotion and Disease Prevention; Hepatocytes; Hepatocytes - drug effects; High fat diet; Humans; Immunohistochemistry; Insulin; Internal Medicine; Lipid metabolism; Lipid Metabolism - drug effects; Lipids; Liver - pathology; Liver diseases; Male; Medicine; Medicine & Public Health; Metabolic Diseases; Metabolic disorders; Metabolic syndrome; Mice; Mice, Inbred C57BL; Nutrition research; Obesity; Obesity - complications; Obesity - metabolism; original-article; Physiological aspects; Prediabetic State - complications; Prediabetic State - metabolism; Proteins; Public Health; Receptors; Steatosis; Streptozocin; Translocase
• ISSN: 0307-0565; 1476-5497
• DOI: 10.1038/ijo.2016.90

Background and objectives: Obesity is a global epidemic which increases the risk of the metabolic syndrome. Cathelicidin (LL-37 and mCRAMP) is an antimicrobial peptide with an unknown role in obesity. We hypothesize that cathelicidin expression correlates with obesity and modulates fat mass and hepatic steatosis. Materials and methods: Male C57BL/6 J mice were fed a high-fat diet. Streptozotocin was injected into mice to induce diabetes. Experimental groups were injected with cathelicidin and CD36 overexpressing lentiviruses. Human mesenteric fat adipocytes, mouse 3T3-L1 differentiated adipocytes and human HepG2 hepatocytes were used in the in vitro experiments. Cathelicidin levels in non-diabetic, prediabetic and type II diabetic patients were measured by enzyme-linked immunosorbent assay. Results: Lentiviral cathelicidin overexpression reduced hepatic steatosis and decreased the fat mass of high-fat diet-treated diabetic mice. Cathelicidin overexpression reduced mesenteric fat and hepatic fatty acid translocase (CD36) expression that was reversed by lentiviral CD36 overexpression. Exposure of adipocytes and hepatocytes to cathelicidin significantly inhibited CD36 expression and reduced lipid accumulation. Serum cathelicidin protein levels were significantly increased in non-diabetic and prediabetic patients with obesity, compared with non-diabetic patients with normal body mass index (BMI) values. Prediabetic patients had lower serum cathelicidin protein levels than non-diabetic subjects. Conclusions: Cathelicidin inhibits the CD36 fat receptor and lipid accumulation in adipocytes and hepatocytes, leading to a reduction of fat mass and hepatic steatosis in vivo . Circulating cathelicidin levels are associated with increased BMI. Our results demonstrate that cathelicidin modulates the development of obesity.