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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
University of Pennsylvania, Perelman School of Medicine, Department of Medicine, Gastroenterology Division, Philadelphia, Pennsylvania, United States of America.
Rotonya M
RM
Carr
University of Pennsylvania, Perelman School of Medicine, Institute for Diabetes, Obesity and Metabolism, Philadelphia, Pennsylvania, United States of America.
Giselle
G
Peralta
University of Pennsylvania, Perelman School of Medicine, Institute for Diabetes, Obesity and Metabolism, Philadelphia, Pennsylvania, United States of America.
Xiaoyan
X
Yin
University of Pennsylvania, Perelman School of Medicine, Institute for Diabetes, Obesity and Metabolism, Philadelphia, Pennsylvania, United States of America.
Rexford S
RS
Ahima
D000818:Animals; D001823:Body Composition; D001835:Body Weight; D002518:Ceramides / Q000378:metabolism*; D015536:Down-Regulation; D000431:Ethanol / Q000008:administration & dosage*; D005234:Fatty Liver / Q000378:metabolism*; D018149:Glucose Intolerance / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006706:Homeostasis; D050356:Lipid Metabolism / Q000502:physiology; D008099:Liver / Q000378:metabolism; D008108:Liver Diseases, Alcoholic / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010101:Oxygen Consumption; D000070780:Perilipin-2; D013997:Time Factors; D014280:Triglycerides / Q000378:metabolism
D002518:Ceramides; D008565:Membrane Proteins; D000070780:Perilipin-2; C000602983:Plin2 protein, mouse; D014280:Triglycerides; D000431:Ethanol