Induction of overlapping genes by fasting and a peroxisome proliferator in pigs: evidence of functional PPARalpha in nonproliferating species.
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.
Cheon
Yewon
Y
Division of Nutritional Sciences, Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, 905 South Goodwin Ave., Bevier Hall #439, Urbana, IL, USA.
Nara
Takayuki Y
TY
Band
Mark R
MR
Beever
Jonathan E
JE
Wallig
Matthew A
MA
Nakamura
Manabu T
MT
D000818:Animals; D002784:Cholesterol / Q000378:metabolism; D002995:Clofibric Acid / Q000494:pharmacology; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D015342:DNA Probes; D005215:Fasting / Q000502:physiology*; D005227:Fatty Acids / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D015723:Gene Library; D007657:Ketone Bodies / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008112:Liver Glycogen / Q000378:metabolism; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D047493:PPAR alpha / Q000235:genetics* / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013552:Swine
D015342:DNA Probes; D005227:Fatty Acids; D007657:Ketone Bodies; D008112:Liver Glycogen; D047493:PPAR alpha; D012333:RNA, Messenger; D002995:Clofibric Acid; D004247:DNA; D002784:Cholesterol