Poster Presentation Australian Diabetes Society and the Australian Diabetes Educators Association Annual Scientific Meeting 2014

Perilipin-5 facilitates fatty acid oxidation and inhibits excessive triglyceride secretion in the liver. (#232)

Stacey N Keenan 1
  1. Department of Physiology, Monash University, Clayton, Victoria, Australia

Lipid metabolism is highly regulated and requires the co-ordinate actions of hormones and proteins to maintain homeostasis and prevent excessive lipid accumulation, which is linked to the pathogenesis of several metabolic diseases. The perilipin (Plin) proteins are abundant lipid droplet associated proteins, providing stabilization of intracellular lipid droplets and the control of triglyceride lipolysis. Plin5 is an important regulator of cardiac lipid metabolism and is highly expressed in other oxidative tissues, such as the liver and muscle. The aim of this study was to investigate the role of Plin5 in regulating lipid metabolism in hepatocytes. Hepatocytes were isolated by collagenase digestion from the livers of whole-body Plin5-/- and Plin5+/+ mice and were cultured for one day prior to the assessment of lipid metabolism by radiometric methods. Fatty acid uptake and storage into intracellular acylglycerols was not significantly different between Plin5-/- and Plin5+/+ hepatocytes. Plin5 ablation decreased the oxidation of free fatty acids by 35% and intrahepatic triglyceride-derived fatty acids by 69% compared with Plin5+/+ hepatocytes. The decrease in fatty acid oxidation was not due to defects in mitochondrial respiration. Treatment of hepatocytes with glucose resulted in increased lipogenesis (76%) in Plin5-/- compared with Plin5+/+ hepatocytes. Triglyceride secretion from hepatocytes was increased nearly 4-fold with Plin5 deletion. Thus, we conclude that Plin5 is essential for maintaining lipid homeostasis, by facilitating fatty acid oxidation and inhibiting excessive triglyceride secretion.