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Journal of Lipid Research, Vol. 45, 2025-2037, November 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology

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

Susanna S. T. Lee^1,*, Wood-Yee Chan, Cherry K. C. Lo^*, David C. C. Wan^*, David S. C. Tsang^* and Wing-Tai Cheung^*

^* Department of Biochemistry, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China
Department of Anatomy, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China

¹ To whom correspondence should be addressed. e-mail: lee2022{at}cuhk.edu.hk

The peroxisome proliferator-activated receptor (PPAR) 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 PPAR-null (KO) mice and their wild-type (WT) counterparts were investigated. Our results indicated that mice deficient in PPAR 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 PPAR plays an important role in regulation of fatty acid metabolism as well as phospholipid homeostasis during energy deprivation.

Abbreviations: KO, PPAR-null [knockout]; PL, phospholipid; WT, wild-type

Supplementary key words adipose tissue • arachidonic acid • docosahexaenoic acid • fatty acid profiling • fatty liver • hepatomegaly • 3-hydroxy-3-methylglutaryl coenzyme A synthase • hypoketonemia • ketone bodies • peroxisome proliferator-activated receptor • starvation

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