Absence of perilipin 2 prevents hepatic steatosis, glucose intolerance and ceramide accumulation in alcohol-fed mice

• Published in: PloS one Vol. 9; no. 5; p. e97118
• Main Authors: Carr, Rotonya M, Peralta, Giselle, Yin, Xiaoyan, Ahima, Rexford S
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 15.05.2014; Public Library of Science (PLoS)
• Subjects: Accumulation; Alcoholic beverages; Alcoholism; Analysis; Animals; Biology; Blood glucose test; Body Composition; Body composition (biology); Body Weight; Carbohydrates; Carbon dioxide; Ceramide; Ceramides - metabolism; Composition effects; Diabetes; Diet; Down-Regulation; Drug tolerance; Energy balance; Energy intake; Enzymes; Ethanol; Ethanol - administration & dosage; Fatty liver; Fatty Liver - metabolism; Feeding; Gastroenterology; Glucose; Glucose intolerance; Glucose Intolerance - metabolism; Glucose tolerance; Glucose Tolerance Test; Hepatology; Histology; Homeostasis; In vivo methods and tests; Insulin resistance; Intolerance; Lipid Metabolism - physiology; Lipids; Lipogenesis; Liver; Liver - metabolism; Liver cirrhosis; Liver diseases; Liver Diseases, Alcoholic - pathology; Male; Medicine; Medicine and Health Sciences; Membrane Proteins - genetics; Membrane Proteins - physiology; Metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Obesity; Oxygen; Oxygen Consumption; Pathogenesis; Perilipin-2; Physiological aspects; Physiology; Prevention; Proteins; Rodents; Steatosis; Studies; Time Factors; Triglycerides; Triglycerides - metabolism; United States > US; Pennsylvania
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0097118

Perilipin 2 (Plin2) is a lipid droplet protein that has roles in both lipid and glucose homeostasis. An increase in Plin2 in liver is associated with the development of steatosis, glucose intolerance, and ceramide accumulation in alcoholic liver disease. We investigated the role of Plin2 on energy balance and glucose and lipid homeostasis in wildtype and Plin2 knockout (Plin2KO) mice chronically fed a Lieber-DeCarli liquid ethanol or control diet for six weeks. We performed in vivo measurements of energy intake and expenditure; body composition; and glucose tolerance. After sacrifice, liver was dissected for histology and lipid analysis. We found that neither genotype nor diet had a significant effect on final weight, body composition, or energy intake between WT and Plin2KO mice fed alcohol or control diets. Additionally, alcohol feeding did not affect oxygen consumption or carbon dioxide production in Plin2KO mice. We performed glucose tolerance testing and observed that alcohol feeding failed to impair glucose tolerance in Plin2KO mice. Most notably, absence of Plin2 prevented hepatic steatosis and ceramide accumulation in alcohol-fed mice. These changes were related to downregulation of genes involved in lipogenesis and triglyceride synthesis. Plin2KO mice chronically fed alcohol are protected from hepatic steatosis, glucose intolerance, and hepatic ceramide accumulation, suggesting a critical pathogenic role of Plin2 in experimental alcoholic liver disease.