書誌： Age , 2013
Chujo Y, Fujii N, Okita N, Konishi T, Narita T, Yamada A, Haruyama Y, Tashiro K, Chiba T, Shimokawa I, Higami Y. (2013). Age (Dordr). 35(4):1143-56. doi: 10.1007/s11357-012-9439-1. Abstract The role of the growth hormone (GH)-insulin-like growth factor (IGF)-1 axis in the lifelong caloric restriction (CR)-associated remodeling of white adiposetissue (WAT), adipocyte size, and gene expression profiles was explored in this study. We analyzed the WAT morphology of 6–7-month-old wild-type Wistarrats fed ad libitum (WdAL) or subjected to CR (WdCR),and of heterozygous transgenic dwarf rats bearing ananti-sense GH transgene fed ad libitum (TgAL) or subjected to CR (TgCR). Although less effective in TgAL, the adipocyte size was significantly reduced in WdCR compared with WdAL. This CR effect was blunted inTg rats. We also used high-density oligonucleotide microarrays to examine the gene expression profile ofWAT of WdAL, WdCR, and TgAL rats. The gene expression profile of WdCR, but not TgAL, differed greatly from that of WdAL. The gene clusters with the largest changes induced by CR but not by Tg were genes involved in lipid biosynthesis and inflammation, particularly sterol regulatory element binding proteins(SREBPs)-regulated and macrophage-related genes, respectively. Real-time reverse-transcription polymerasechain reaction analysis confirmed that the expression of SREBP-1 and its downstream targets was upregulated, whereas the macrophage-related genes were downregulated in WdCR, but not in TgAL. In addition, CR affected the gene expression profile of Tg rats similarly to wild-type rats. Our findings suggest that CR-associated remodeling of WAT, which involvesSREBP-1-mediated transcriptional activation and suppression of macrophage infiltration, is regulated in aGH–IGF-1-independent manner. Keywords: Growth hormone. Insulin-like growth factor-1. Caloric restriction (CR). Lipid biosynthesis. Sterol regulatory element binding protein. DNA microarray