Induction of overlapping genes by fasting and a peroxisome proliferator in pigs: Evidence of functional PPARα in nonproliferating species

Department of Animal Sciences, University of Illinois, Urbana-Champaign, Urbana, Illinois, United States
AJP Regulatory Integrative and Comparative Physiology (Impact Factor: 3.11). 07/2005; 288(6):R1525-35. DOI: 10.1152/ajpregu.00751.2004
Source: PubMed


Peroxisome proliferator-activated receptor alpha (PPARalpha), a key regulator of fatty acid oxidation, is essential for adaptation to fasting in rats and mice. However, physiological functions of PPARalpha in other species, including humans, are controversial. A group of PPARalpha ligands called peroxisome proliferators (PPs) causes peroxisome proliferation and hepatocarcinogenesis only in rats and mice. To elucidate the role of PPARalpha in adaptation to fasting in nonproliferating species, we compared gene expressions in pig liver from fasted and clofibric acid (a PP)-fed groups against a control diet-fed group. As in rats and mice, fasting induced genes involved with mitochondrial fatty acid oxidation and ketogenesis in pigs. Those genes were also induced by clofibric acid feeding, indicating that PPARalpha mediates the induction of these genes. In contrast to rats and mice, little or no induction of genes for peroxisomal or microsomal fatty acid oxidation was observed in clofibric acid-fed pigs. Histology showed no significant hyperplasia or hepatomegaly in the clofibric acid-fed pigs, whereas it showed a reduction of glycogen by clofibric acid, an effect of PPs also observed in rats. Copy number of PPARalpha mRNA was higher in pigs than in mice and rats, suggesting that peroxisomal proliferation and hyperresponse of several genes to PPs seen only in rats and mice are unrelated to the abundance of PPARalpha. In conclusion, PPARalpha is likely to play a central role in adaptation to fasting in pig liver as in rats and mice.

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Available from: Matthew Wallig, Jan 26, 2016
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    • "Likewise, the present findings underscore that H group increased the expression of gene sets regulated by peroxisome proliferator-activated receptors alpha (PPAR-α) (APOA2, CYP2C9, CYP2C19) and RXR (ABCG8, CYP7A1) transcription factors, both of which are shown to have an important role in lipid homeostasis. For instance, PPAR-α is an important regulator of cellular fatty acid uptake and intracellular fatty acid transport, mitochondrial and peroxisomal fatty acid oxidation, ketogenesis, and gluconeogenesis in several species [41-43], whereas RXR plays a crucial role in the transcriptional regulation of a spectrum of genes controlling cholesterol homeostasis and bile acid homeostasis, together with nuclear receptor FXR, a key transcription factor that regulates cholesterol 7 α-hydroxylase (CYP7A1) activity and mRNA levels. "
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    • "Regarding expression of PPARα, there is, however, a different tissue profile between pigs and rats. Expression of PPARα in the liver is much lower in pigs than in rodents (Cheon et al., 2005; Luci et al., 2007). In contrast, pigs have a considerable expression of PPARα in the white adipose tissue (Ding et al., 2000) while in rats it is nearly completely absent in adipose tissue (Escher et al., 2001). "
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