title: θ-Defensin RTD-1 improves insulin action and normalizes plasma glucose and FFA levels in diet-induced obese rats.
abstract: Inflammation is implicated in metabolic abnormalities in obesity and type 2 diabetes. Because θ-defensins have anti-inflammatory activities, we tested whether RTD-1, a θ-defensin, improves metabolic conditions in diet-induced obesity (DIO). DIO was induced by high-fat feeding in obese-prone CD rats from 4 wk of age. Starting at age 10 wk, the DIO rats were treated with saline or RTD-1 for 4 or 8 wk. DIO rats gained more weight than low-fat-fed controls. RTD-1 treatment did not alter body weight or calorie intake in DIO rats. Plasma glucose, FFA, triglyceride (TG), and insulin levels increased in DIO rats; RTD-1 normalized plasma glucose and FFA levels and showed tendencies to lower plasma insulin and TG levels. Hepatic and skeletal muscle TG contents increased in DIO rats; RTD-1 decreased muscle, but not hepatic, TG content. Insulin sensitivity, estimated using homeostasis model assessment of insulin resistance and the glucose clamp technique, decreased in DIO rats, but this change was markedly reversed by RTD-1. RTD-1 had no significant effects on plasma cytokine/chemokine levels or IL-1β and TNF-α expression in liver or adipose tissues. RTD-1 treatment decreased hepatic expression of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase, suggesting that the effect of RTD-1 on plasma glucose (or insulin action) might be mediated by its effect to decrease hepatic gluconeogenesis. Thus, RTD-1 ameliorated insulin resistance and normalized plasma glucose and FFA levels in DIO rats, supporting the potential of RTD-1 as a novel therapeutic agent for insulin resistance, metabolic syndrome, or type 2 diabetes.
authors.affiliation: Departments of Physiology and Biophysics, University of Southern California Keck School of Medicine, Los Angeles, California;
authors.forename: Young Taek
authors.initials: YT
authors.lastname: Oh
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Southern California Keck School of Medicine, Los Angeles, California;
authors.forename: Dat
authors.initials: D
authors.lastname: Tran
authors.affiliation: Department of Medicine, University of Southern California Keck School of Medicine, Los Angeles, California; and.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Buchanan
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Southern California Keck School of Medicine, Los Angeles, California; Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, California.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Selsted
authors.affiliation: Departments of Physiology and Biophysics, University of Southern California Keck School of Medicine, Los Angeles, California; youn@usc.edu.
authors.forename: Jang H
authors.initials: JH
authors.lastname: Youn
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D023082:Defensins / Q000494:pharmacology* / Q000627:therapeutic use; D059305:Diet, High-Fat; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D007328:Insulin / Q000097:blood / Q000502:physiology*; D007333:Insulin Resistance; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D009765:Obesity / Q000097:blood / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D051381:Rats; D014280:Triglycerides / Q000097:blood
chemical_list: D001786:Blood Glucose; D023082:Defensins; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D014280:Triglycerides; C450142:theta-defensin
keywords: gluconeogenesis; high-fat feeding; inflammation; insulin resistance; type 2 diabetes