Requirement of PPARα in maintaining phospholipid and triacylglycerol homeostasis during energy deprivation

Abstract

The peroxisome proliferator-activated receptor α (PPARα) has been implicated as a key control of fatty acid catabolism during the cellular fasting. However, little is known regarding changes of individual fatty acids in hepatic triacylglycerol (TG) and phospholipid (PL) as a result of starvation. In the present work, the effects of 72 h fasting on hepatic TG and PL fatty acid profiles in PPARα-null (KO) mice and their wild-type (WT) counterparts were investigated. Our results indicated that mice deficient in PPARα displayed hepatomegaly and hypoketonemia following 72 h starvation. Histochemical analyses revealed that severe fatty infiltration was observed in the livers of KO mice under fasted conditions. Furthermore, 72 h fasting resulted in a 2.8-fold higher accumulation of hepatic TG in KO mice than in WT mice fasted for the same length of time. Surprisingly, the total hepatic PL contents in fasted KO mice decreased by 45%, but no significant change in hepatic PL content was observed in WT mice following starvation. Gas chromatographic analysis indicated that KO mice were deprived of arachidonic (20:4n-6) and docosahexaenoic (22:6n-3) acids during fasting.Taken together, these results show that PPARα plays an important role in regulation of fatty acid metabolism as well as phospholipid homeostasis during energy deprivation.

Keywords

• adipose tissue
• arachidonic acid
• docosahexaenoic acid
• fatty acid profiling
• fatty liver
• hepatomegaly