Adipose tissue energy metabolism: altered gene expression profile of mice subjected to long-term caloric restriction.

We investigated the influences of short-term and lifespan-prolonging long-term caloric restriction (LCR) on gene expression in white adipose tissue (WAT). Over 11,000 genes were examined using high-density oligonucleotide microarrays in four groups of 10- to 11-month-old male C57Bl6 mice that were either fasted for 18 h before death (F), subjected to short-term caloric restriction for 23 days (SCR), or LCR for 9 months and compared with nonfasted control (CO) mice. Only a few transcripts of F and SCR were differentially expressed compared with CO mice. In contrast, 345 transcripts of 6,266 genes found to be expressed in WAT were altered significantly by LCR. The expression of several genes encoding proteins involved in energy metabolism was increased by LCR. Further, many of the shifts in gene expression after LCR are known to occur during adipocyte differentiation. Selected LCR-associated alterations of gene expression were supported by quantitative reverse transcriptase-polymerase chain reaction, histology, and histochemical examinations. Our data provide new insights on the metabolic state associated with aging retardation by LCR.