title: Cathelicidin suppresses lipid accumulation and hepatic steatosis by inhibition of the CD36 receptor.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: D
authors.initials: D
authors.lastname: Hoang-Yen Tran
authors.affiliation: Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: D
authors.initials: D
authors.lastname: Hoang-Ngoc Tran
authors.affiliation: Department of Medicine, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Mattai
authors.affiliation: Department of Medicine, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: T
authors.initials: T
authors.lastname: Sallam
authors.affiliation: Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Ortiz
authors.affiliation: Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: E C
authors.initials: EC
authors.lastname: Lee
authors.affiliation: Department of Medicine, Cedars-Sinai Medical Center, F. Widjaja Foundation, Inflammatory Bowel & Immunobiology Research Institute, Los Angeles, CA, USA.
authors.forename: L
authors.initials: L
authors.lastname: Robbins
authors.affiliation: Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Ho
authors.affiliation: Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Lee
authors.affiliation: Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: E
authors.initials: E
authors.lastname: Fisseha
authors.affiliation: Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Shieh
authors.affiliation: Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Sideri
authors.affiliation: Department of Medicine, Cedars-Sinai Medical Center, F. Widjaja Foundation, Inflammatory Bowel & Immunobiology Research Institute, Los Angeles, CA, USA.
authors.forename: D Q
authors.initials: DQ
authors.lastname: Shih
authors.affiliation: Department of Medicine, Cedars-Sinai Medical Center, F. Widjaja Foundation, Inflammatory Bowel & Immunobiology Research Institute, Los Angeles, CA, USA.
authors.forename: P
authors.initials: P
authors.lastname: Fleshner
authors.affiliation: Department of Medicine, Cedars-Sinai Medical Center, F. Widjaja Foundation, Inflammatory Bowel & Immunobiology Research Institute, Los Angeles, CA, USA.
authors.forename: D P B
authors.initials: DP
authors.lastname: McGovern
authors.affiliation: Department of Medicine, Cedars-Sinai Medical Center, F. Widjaja Foundation, Inflammatory Bowel & Immunobiology Research Institute, Los Angeles, CA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Vu
authors.affiliation: Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: T C
authors.initials: TC
authors.lastname: Hing
authors.affiliation: Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: K
authors.initials: K
authors.lastname: Bakirtzi
authors.affiliation: Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Cheng
authors.affiliation: Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: B
authors.initials: B
authors.lastname: Su
authors.affiliation: Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: I
authors.initials: I
authors.lastname: Law
authors.affiliation: Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: I
authors.initials: I
authors.lastname: Karagiannides
authors.affiliation: Department of Medicine, Cedars-Sinai Medical Center, F. Widjaja Foundation, Inflammatory Bowel & Immunobiology Research Institute, Los Angeles, CA, USA.
authors.forename: S R
authors.initials: SR
authors.lastname: Targan
authors.affiliation: Division of Dermatology, Department of Medicine, the University of California San Diego, San Diego, CA, USA.
authors.forename: R L
authors.initials: RL
authors.lastname: Gallo
authors.affiliation: Division of Clinical Nutrition, Department of Medicine, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Li
authors.affiliation: Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: H W
authors.initials: HW
authors.lastname: Koon
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D018955:CD36 Antigens / Q000096:biosynthesis / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental; D059305:Diet, High-Fat / Q000009:adverse effects; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control*; D005786:Gene Expression Regulation / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D050356:Lipid Metabolism / Q000187:drug effects*; D008099:Liver / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000150:complications / Q000378:metabolism; D011236:Prediabetic State / Q000150:complications / Q000378:metabolism; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D018955:CD36 Antigens; D054804:Cathelicidins