Hepatic gene expression profile of lipid metabolism in rats: Impact of caloric restriction and growth hormone/insulin-like growth factor-1 suppression.
We investigated the role of the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis on caloric restriction (CR) using male wild-type and transgenic homozygous dwarf rats bearing an antisense GH transgene and their F1 heterozygous progeny fed either ad libitum or subjected to 30% CR. CR predominantly altered expression of hepatic genes involved in the stress response, xenobiotic metabolism, and lipid metabolism. Most gene expressions involved in stress response and xenobiotic metabolism were regulated in a GH/IGF-1-dependent manner, and those involved in lipid metabolism were regulated in a GH/IGF-1-independent manner. Moreover, CR enhanced the gene expression involved in fatty acid synthesis after feeding and those encoding mitochondrial beta-oxidation enzymes during food shortage, probably via transcriptional regulation by peroxisome proliferator-activated receptor alpha. These results, taken together with serum biochemical measures and hepatic triglyceride content, suggest that CR promotes lipid utilization through hepatic transcriptional alteration and prevents hepatic steatosis in a GH/IGF-1-independent manner.
Higami
Yoshikazu
Y
Department of Investigative Pathology, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan. higami@net.nagasaki-u.ac.jp
Tsuchiya
Tomoshi
T
Chiba
Takuya
T
Yamaza
Haruyoshi
H
Muraoka
Izumi
I
Hirose
Megumi
M
Komatsu
Toshimitsu
T
Shimokawa
Isao
I
D000818:Animals; D031204:Caloric Restriction; D005230:Fatty Acids, Nonesterified / Q000097:blood; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D013006:Growth Hormone / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000235:genetics*; D007657:Ketone Bodies / Q000097:blood; D050356:Lipid Metabolism / Q000235:genetics*; D008099:Liver / Q000378:metabolism*; D008297:Male; D047493:PPAR alpha / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019076:Transgenes; D014280:Triglycerides / Q000378:metabolism
D005230:Fatty Acids, Nonesterified; D007657:Ketone Bodies; D047493:PPAR alpha; D014280:Triglycerides; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone