Physiologic Roles of Hepatic Lipid Droplets and Involvement of Peroxisome Proliferator-Activated Receptor .ALPHA. in Their Dynamism

Abstract

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 a a (PPARa a)-null mice fed various natural diets by identifying the liver-enriched LDassociated 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 PPARa a-dependent manner.

PPARαas a Transcriptional Regulator for Detoxification of Plant Diet-Derived Unfavorable Compounds

“…Feeding these seeds and nuts induced the formation of lipid droplets with similar fatty acid compositions to those of the diets in the liver of both wild-type and PPAR α -null mice [17]. Thus, the fatty acid compositions of neutral lipids in hepatic lipid droplets were strongly influenced by those in the diet, suggesting that the lipid droplets promptly stored the diet-derived excess fats with unfavorable fatty acid compositions and protected the cells from lipotoxicity.…”

“…However, quick reversibility was not observed in PPAR α -null mice. These results suggest that PPAR α plays an important role in the rapid induction of lipid-metabolizing/remodeling enzymes according to the contents of the diet [17]. However, PPAR α may not be absolutely necessary for metabolism of major fatty acids but vital for detoxification of minor but sesame-enriched abnormal fatty acid(s) or compound(s).…”