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

Department of Investigative Pathology, Nagasaki University Graduate School of Biomedical Sciences, Japan.

Address correspondence to Yoshikazu Higami, MD, PhD, Department of Investigative Pathology, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan. E-mail: higami{at}net.nagasaki-u.ac.jp

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

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