title: Glucocorticoid inhibition of leptin- and lipopolysaccharide-induced interleukin-6 production in obesity.
abstract: Obesity is considered a chronic inflammatory condition that enhances the risk of numerous inflammatory diseases, including diabetes and cardiovascular disease. Glucocorticoids (GCs) and synthetic therapeutic GCs are anti-inflammatory agents, but the exact functions of GCs in obesity-related inflammation are unknown. Therefore, the objective of this study was to examine the inhibitory effect of an exogenous GC (dexamethasone, DEX) on leptin- and lipopolysaccharide (LPS)-induced IL-6 production by peripheral blood mononuclear cells (PBMCs) ex vivo in obese subjects compared to normal-weight subjects. Blood samples were drawn from 14 obese (BMI>30 kg/m(2)) and 14 normal-weight (BMI<25 kg/m(2)) subjects. Plasma cortisol, TNF-α and IL-6 levels, and insulin resistance (HOMA-IR) were quantified. Subjects' PBMCs (1×10(6) cells/mL) were isolated and cultured with leptin (18.75 and 250 ng/mL) or LPS (10ng/mL) in the presence of DEX (0, 10(-8), 10(-7), and 10(-6) M), a synthetic GC, for 24 h; IL-6 levels and GC sensitivity (IC50) were assessed in the cultured supernatants. No differences in the plasma cortisol levels were found between the two groups. We found that obese subjects showed greater leptin- and LPS-induced IL-6 production compared to normal-weight subjects. The suppressive effect of DEX on leptin- and LPS-induced IL-6 production (IC50) was not different between the two groups. However, the IC50 of DEX for LPS-induced was correlated with BMI, waist circumference, and hip circumference. These findings suggest that reduced GC sensitivity may be an important mechanism in the up-regulation of selected obese inflammation.
authors.affiliation: Department of Exercise Science and Health Promotion, Florida Atlantic University, Boca Raton, FL, United States. Electronic address: chuang5@fau.edu.
authors.forename: Chun-Jung
authors.initials: CJ
authors.lastname: Huang
authors.affiliation: Department of Health and Human Performance, Virginia Commonwealth University, Richmond, VA, United States.
authors.forename: Edmund O
authors.initials: EO
authors.lastname: Acevedo
authors.affiliation: Department of Exercise Science and Health Promotion, Florida Atlantic University, Boca Raton, FL, United States.
authors.forename: David C
authors.initials: DC
authors.lastname: Mari
authors.affiliation: Department of Exercise Science and Health Promotion, Florida Atlantic University, Boca Raton, FL, United States.
authors.forename: Christopher
authors.initials: C
authors.lastname: Randazzo
authors.affiliation: Department of Biomedical Science, College of Medicine, Florida Atlantic University, Boca Raton, FL, United States.
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Shibata
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism / Q000502:physiology*; D020738:Leptin / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D009765:Obesity / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D055815:Young Adult
chemical_list: D005938:Glucocorticoids; D015850:Interleukin-6; D020738:Leptin; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D006854:Hydrocortisone
keywords: Glucocorticoid sensitivity; Interleukin-6; Leptin; Lipopolysaccharide; Obesity