Functional Study of Porcine Peroxisome Proliferator-Activated Receptor γ and δ
Date Issued
2009
Date
2009
Author(s)
Yu, Yu-Hsiang
Abstract
Peroxisome proliferator-activated receptor γ (PPARγ) is a transcription factor that promotes adipocyte differentiation and insulin sensitivity. The PPARδ are multifunctional roles in lipid metabolism, specifically on lipolysis in the adipose tissue and fatty acid oxidation in the skeletal muscle. A ligand for PPARγ and PPARδ is required to activate PPARγ and PPARδ function. Fatty acids and its derivatives have been proposed to be the endogenous ligands for PPARγ and PPARδ. Polyunsaturated fatty acids (PUFA) have good binding activities with PPARγ and PPARδ. However, no direct evidence PUFA regulate lipid metabolism through activation of PPARγ and PPARδ in vivo. The current experiment was designed to study the function of porcine PPARγ and PPARδ in lipid metabolism.e found that porcine wild-type PPARγ and mutated PPARγ (serine 112 was mutated to alanine) enhanced the conversion of myoblast cells into adipocytes and the ability to transdifferentiation was greater in cells containing the mutated PPARγ than in cells containing the wild-type PPARγ. Therefore, the existence of serine 112 in PPARγ may have a role in regulating adipocyte differentiation. In the second experiment, we demonstrated that in myoblasts transfected with porcine PPARδ, adipogenesis was promoted in the presence of a PPARγ ligand. In addition, we showed that PPARδ alone with its ligand modulated adipogenic genes via expression of endogenous PPARγ. The third experiment demonstrated that docosahexaenoic acid (DHA) was a potent ligand precursor for porcine PPARγ activation. The DHA itself did not directly activate PPARγ but waking through its metabolites. In the in vivo study, we generated two transgenic mice models to study the function of PPARγ and PPARδ. One is muscle-specific expression of porcine PPARγ (PPARγ transgenic mice), and the other is adipose tissue-specific expression of PPARδ (PPARδ transgenic mice). Transgenic mice were generated and fed with high-saturated fat (13% beef tallow) or high-unsaturated fat (13% fish oil) diets for 4 months. Compared with wild-type mice, fish oil feeding increased glucose metabolism in PPARγ transgenic mice and reduced fat deposition, plasma triacylglycerol and free fatty acids in PPARδ transgenic mice. The results indicate PUFA may serves as natural and effective regulator of glucose and lipid metabolism in vivo and these effects may generate from activation of PPARγ and PPARδ.n conclusion, we demonstrated that porcine PPARγ and PPARδ play an important role in regulating lipid metabolism. Transgenic mouse models provide direct evidences to demonstrate PUFA, especially from fish oil, regulate glucose metabolism and lipid metabolism through interaction with PPARγ and PPARδ, respectively.
Subjects
adipocyte
lipid metabolism
peroxisome proliferator-activated receptor γ
peroxisome proliferator-activated receptor δ
polyunsaturated fatty acids
pigs
Type
thesis
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