Hepatic Gene Expression Profile of Lipid Metabolism in Rats: Impact of Caloric Restriction and Growth Hormone/Insulin-Like Growth Factor-1 Suppression

• Published in: The journals of gerontology. Series A, Biological sciences and medical sciences Vol. 61; no. 11; pp. 1099 - 1110
• Main Authors: Higami, Yoshikazu, Tsuchiya, Tomoshi, Chiba, Takuya, Yamaza, Haruyoshi, Muraoka, Izumi, Hirose, Megumi, Komatsu, Toshimitsu, Shimokawa, Isao
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01-11-2006
• Subjects: Age; Aging; Animals; Caloric Restriction; Fatty Acids, Nonesterified - blood; Gene expression; Gene Expression Profiling; Gene Expression Regulation; Genetic engineering; Growth Hormone - genetics; Growth hormones; Insulin; Insulin-Like Growth Factor I - analysis; Insulin-Like Growth Factor I - genetics; Ketone Bodies - blood; Laboratory animals; Lipid Metabolism - genetics; Lipids; Liver; Liver - metabolism; Male; PPAR alpha - metabolism; Rats; Reverse Transcriptase Polymerase Chain Reaction; Rodents; Transgenes; Triglycerides - metabolism
• ISSN: 1079-5006; 1758-535X
• DOI: 10.1093/gerona/61.11.1099

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 β-oxidation enzymes during food shortage, probably via transcriptional regulation by peroxisome proliferator-activated receptor α. 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.