Aging is associated with redistribution of body fat and the development of insulin resistance. White adipose tissue emerges as an important organ in controlling life span. Caloric restriction (CR) delays the rate of aging possibly modulated partly by altering the amount and function of adipose tissue. Adiponectin is a major adipose-derived adipokine that has anti-inflammatory and insulin-sensitizing properties. This study examined the effects of CR on adiposity and gene expression of adiponectin, its receptors (AdipoR1 and AdipoR2) in adipose tissue and in isolated adipocytes of Brown Norway rats that had undergone CR for 4 months or fed ad libitum. The study also determined plasma concentrations of adiponectin and insulin in these animals and whether insulin infusion for 7 days affects adiponectin expression and its circulating concentrations under CR conditions. CR markedly reduced body weight as anticipated, epididymal fat mass and adipocyte size. CR led to an increase in plasma free fatty acid and glycerol (both twofold), and adipose triglyceride lipase messenger RNA (mRNA) in adipose tissue and isolated adipocytes (both >2-fold). Adiponectin mRNA levels were elevated in adipose tissue and adipocytes (both >2-fold) as was plasma adiponectin concentration (2.8-fold) in CR rats. However, CR did not alter tissue or cellular AdipoR1 and AdipoR2 expression. Seven days of insulin infusion decreased adiponectin mRNA in adipose tissue but did not reverse the CR-induced up-regulation of circulating adiponectin levels. Our results suggest that the benefits of CR could be, at least in part, dependent on enhanced expression and secretion of adiponectin by adipocytes.

It is accepted that dietary restriction (DR) feeding regimes will extend life span and even slow the rate of aging in a wide range of invertebrate and vertebrate species. In spite of significant research effort however, the biochemical mechanism underlying this effect still remains to be resolved. Although a body of data supports the interpretation that DR feeding regimes reduce the intensity of oxidative stress and damage in tissues of older animals, direct experimental confirmation is lacking that manipulating oxidative stress will modify the rate of aging. In tissues from rodent species the major cause of reduced exposure to reactive oxygen species (ROS) under DR feeding conditions results from a lower rate of ROS generation at the mitochondria. Recent work has suggested a plausible explanation of how DR feeding induces this adaptive response. What remains unclear is the cellular target in both fully fed and DR fed animals that is sensitive to ROS and thereby determines the rate of aging. Switching rodents between feeding regimes in mid-life or later provides little evidence of a memory effect of the initial feeding regime on ultimate life-time survival. This observation does not therefore support the interpretation that the extended survival induced by DR feeding results from a slower life time rate of accrual of oxidative damage. The use of a small molecular mimetic of the DR effect may provide an alternative experimental approach to identify the mechanism underlying the extended survival observed.