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Inhibition of ADRP prevents diet-induced insulin resistance.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Varela, Gladys M. Antwi, Daniel A. Dhir, Ravindra Yin, Xiaoyan Singhal, Neel S. Graham, Mark J. Crooke, Roseanne M. Ahima, Rexford S.
Description	Country affiliation: United States Author Affiliation: Varela GM ( Department of Medicine, Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania School of Medicine, 415 Curie Blvd., 712A Clinical Research Bldg., Philadelphia, PA 19104, USA.)
Abstract	Diets with high fat content induce steatosis, insulin resistance, and type 2 diabetes. The lipid droplet protein adipose differentiation-related protein (ADRP) mediates hepatic steatosis, but whether this affects insulin action in the liver or peripheral organs in diet-induced obesity is uncertain. We fed C57BL/6J mice a high-fat diet and simultaneously treated them with an antisense oligonucleotide (ASO) against ADRP for 4 wk. Glucose homeostasis was assessed with clamp and tracer techniques. ADRP ASO decreased the levels of triglycerides and diacylglycerol in the liver, but fatty acids, long-chain fatty acyl CoAs, ceramides, and cholesterol were unchanged. Insulin action in the liver was enhanced after ADRP ASO treatment, whereas muscle and adipose tissue were not affected. ADRP ASO increased the phosphorylation of insulin receptor substrate (IRS)1, IRS2, and Akt, and decreased gluconeogenic enzymes and PKCepsilon, consistent with its insulin-sensitizing action. These results demonstrate an important role for ADRP in the pathogenesis of diet-induced insulin resistance.
File Format	HTM / HTML
ISSN	01931857
e-ISSN	15221547
DOI	10.1152/ajpgi.90204.2008
Journal	AJP: Gastrointestinal and Liver Physiology
Issue Number	3
Volume Number	295
Language	English
Publisher	American Physiological Society
Publisher Date	2008-09-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Physiology Discipline Gastroenterology Fatty Liver Therapy Genetic Therapy Insulin Resistance Membrane Proteins Metabolism Oligonucleotides, Antisense Therapeutic Use Adipose Tissue Enzymology Animals Blood Glucose Dietary Fats Diglycerides Disease Models, Animal Etiology Genetics Physiopathology Homeostasis Insulin Liver Mice Mice, Inbred C57bl Muscle, Skeletal Time Factors Triglycerides Research Support, N.i.h., Extramural
Content Type	Text
Resource Type	Article
Subject	Hepatology Physiology Physiology (medical) Gastroenterology

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