Physiologic roles of hepatic lipid droplets and involvement of peroxisome proliferator-activated receptor alpha in their dynamism.

The liver is not a storage site of excess energy as triacylglycerides but a major site of carbohydrate storage, playing a vital role in glucose homeostasis, and the hepatic lipid droplets (LDs) should have a distinct physiologic role from those in lipid-storing tissues. Most studies so far have been limited to characterization of the LDs in cultured cells or of the liver of animals maintained on a normal laboratory diet, and little is known about the properties of the LDs in the liver responding to dietary excess, irregular fats, and potentially toxic compounds contained in a natural food diet. We started to characterize the hepatic LDs in wild-type and peroxisome proliferator-activated receptor alpha (PPARalpha)-null mice fed various natural diets by identifying the liver-enriched LD-associated proteins and the changes in lipid compositions. Based on the currently available data, we propose the hypothesis that hepatic LDs play vital protective roles against diet-derived excess fatty acids and potentially toxic hydrophobic compounds by temporarily storing them as neutral lipids or compounds until completion of the remodeling of fatty acids and detoxification of the compounds in a PPARalpha-dependent manner.