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.
Subject(s)
Antimicrobial Cationic Peptides/pharmacology , Fatty Liver/drug therapy , Fatty Liver/prevention & control , Lipid Metabolism/drug effects , 3T3-L1 Cells , Adipocytes/cytology , Adipocytes/drug effects , Adipocytes/metabolism , Animals , CD36 Antigens/biosynthesis , CD36 Antigens/genetics , Cell Differentiation/drug effects , Diabetes Mellitus, Experimental , Diet, High-Fat/adverse effects , Disease Models, Animal , Fatty Liver/complications , Fatty Liver/metabolism , Gene Expression Regulation/drug effects , Hepatocytes/drug effects , Humans , Immunohistochemistry , Liver/pathology , Male , Mice , Mice, Inbred C57BL , Obesity/complications , Obesity/metabolism , Prediabetic State/complications , Prediabetic State/metabolism , CathelicidinsABSTRACT
BACKGROUND: Systemic lupus erythematosus is a chronic, multisystem, autoimmune disorder that primarily affects women. Morbidity and mortality have improved for lupus patients during the last 15 years. An increased risk of malignancy in patients with lupus has been shown in some, but not all studies. The purpose of this study was to ascertain cancer risk in lupus patients by linking two disease registries. METHODS: Participants in the Chicago Lupus Cohort included 616 women with lupus who were residents of Cook County, Illinois. They were seen during 1985-1995 at 4 University, inner city, and suburban inpatient and outpatient clinics in Chicago. Malignancies occurring in these subjects during the study interval, 1985-1995, were identified from the Illinois State Cancer Registry by matching name, birthdate, and social security number. Standardized incidence ratios (SIRs) were estimated for all malignancies in this cohort of lupus patients using age, gender, and all race or race-stratified specific cancer incidence data from Cook County, Illinois. RESULTS: The registry linkage study with the Illinois State Cancer Registry documented that 30 women with lupus had a malignancy. The expected number of malignancies for women in the lupus cohort was 15.0. There were 8 cases of breast cancer and 4 each of lung and cervical cancer. In the remaining 14 women, 12 different types of cancers were noted. The SIR and 95% confidence interval (CI) for malignancy for all women with lupus in the study were 2.0 (1.4, 2.9) and lung cancer was the only individual cancer increased in all women--SIR and 95% CI were 3.1 (1.3, 7.9). In the analysis stratified by race, the risk of malignancy (SIR and 95% CI) was increased in Caucasian women, 2.3 (1.4, 3.9). Breast cancer was the only individual cancer increased in Caucasian women with lupus with an SIR and 95% CI of 2.9 (1.4, 6.4). CONCLUSIONS: Lupus patients have an increased risk of malignancy. Breast, lung, and gynecological malignancies were the most common malignancies observed in the cohort and breast cancer was significantly increased in Caucasian women.
