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

Autor:	Hoang-Yen Tran D; Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA., Hoang-Ngoc Tran D; Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA., Mattai SA; Department of Medicine, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA., Sallam T; Department of Medicine, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA., Ortiz C; Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA., Lee EC; Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA., Robbins L; Department of Medicine, Cedars-Sinai Medical Center, F. Widjaja Foundation, Inflammatory Bowel & Immunobiology Research Institute, Los Angeles, CA, USA., Ho S; Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA., Lee JE; Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA., Fisseha E; Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA., Shieh C; Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA., Sideri A; Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA., Shih DQ; Department of Medicine, Cedars-Sinai Medical Center, F. Widjaja Foundation, Inflammatory Bowel & Immunobiology Research Institute, Los Angeles, CA, USA., Fleshner P; Department of Medicine, Cedars-Sinai Medical Center, F. Widjaja Foundation, Inflammatory Bowel & Immunobiology Research Institute, Los Angeles, CA, USA., McGovern DP; Department of Medicine, Cedars-Sinai Medical Center, F. Widjaja Foundation, Inflammatory Bowel & Immunobiology Research Institute, Los Angeles, CA, USA., Vu M; Department of Medicine, Cedars-Sinai Medical Center, F. Widjaja Foundation, Inflammatory Bowel & Immunobiology Research Institute, Los Angeles, CA, USA., Hing TC; Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA., Bakirtzi K; Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA., Cheng M; Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA., Su B; Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA., Law I; Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA., Karagiannides I; Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA., Targan SR; Department of Medicine, Cedars-Sinai Medical Center, F. Widjaja Foundation, Inflammatory Bowel & Immunobiology Research Institute, Los Angeles, CA, USA., Gallo RL; Division of Dermatology, Department of Medicine, the University of California San Diego, San Diego, CA, USA., Li Z; Division of Clinical Nutrition, Department of Medicine, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA., Koon HW; Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA.
Jazyk:	angličtina
Zdroj:	International journal of obesity (2005) [Int J Obes (Lond)] 2016 Sep; Vol. 40 (9), pp. 1424-34. Date of Electronic Publication: 2016 May 10.
DOI:	10.1038/ijo.2016.90
Abstrakt:	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. Competing Interests: All authors disclose no conflict of interest.
Databáze:	MEDLINE
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