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Animal Models

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

International Journal of Obesity volume 40, pages 1424–1434 (2016)Cite this article

Subjects

Abstract

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.

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Acknowledgements

This work was supported by CCFA (#2691), NIH K01(DK084256), and NIH R03 (DK103964) grants to HWK, CCFA (#287244, #3831 & #324000) to MC, SH and DHNTran, and United States PHS grant DK046763 to DQS. Clinical data and specimens were provided by the MIRIAD Biobank. MIRIAD is currently supported by F Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, NIH grant P01DK046763, The European Union Grant 305479, NIDDK Grant DK062413, U54 DE023798 and the Leona M and Harry B Helmsley Charitable Trust.

Author contributions

DHYT, DH-NT and HWK acquired the data and drafted the manuscript. TS, LR, ECL, CO, SH, EF, CS, JEL, AS, MV, TCH, KB, MC, BS, IL and IK acquired the data and revised the manuscript. SAM, RLG, ZL, DQS, PF, DPBMG and SRT provided provision of materials, acquired data and revised the manuscript. HWK approved the final version of manuscript and study supervision.

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Author notes

  1. D Hoang-Yen Tran and D Hoang-Ngoc Tran: These two authors contributed equally to this work.

Authors and Affiliations

  1. Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA

    D Hoang-Yen Tran, D Hoang-Ngoc Tran, C Ortiz, E C Lee, S Ho, J E Lee, E Fisseha, C Shieh, A Sideri, T C Hing, K Bakirtzi, M Cheng, B Su, I Law, I Karagiannides & H W Koon

  2. Department of Medicine, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA

    S A Mattai & T Sallam

  3. Division of Clinical Nutrition, Department of Medicine, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA

    Z Li

  4. Division of Dermatology, Department of Medicine, the University of California San Diego, San Diego, CA, USA

    R L Gallo

  5. Department of Medicine, Cedars-Sinai Medical Center, F. Widjaja Foundation, Inflammatory Bowel & Immunobiology Research Institute, Los Angeles, CA, USA

    L Robbins, D Q Shih, P Fleshner, D P B McGovern, M Vu & S R Targan

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Correspondence to H W Koon.

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Hoang-Yen Tran, D., Hoang-Ngoc Tran, D., Mattai, S. et al. Cathelicidin suppresses lipid accumulation and hepatic steatosis by inhibition of the CD36 receptor. Int J Obes 40, 1424–1434 (2016). https://doi.org/10.1038/ijo.2016.90

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