Plasma adiponectin concentrations are inversely correlated with body fat content (Havel, 2004); that is, they are lowered in obese patients and animals. Adiponectin exerts an antidiabetic effect by sensitizing insulin action and augmenting fatty acid oxidation in the muscles. It also exhibits an antiatherosclerotic effect by attenuating inflammatory insults in the vascular wall. These metabolic and anti-inflammatory effects are also thought to be some of the beneficial effects of CR (Masoro, 2003). Indeed, recent reports demonstrated a higher plasma concentration of adiponectin in CR animals (Berg et al., 2001; Combs et al., 2003; Zhu et al., 2004), and in long-lived dwarf animal models, plasma adiponectin concentrations have been shown to be increased (Berryman et al., 2004).
In this study, plasma adiponectin levels were increased in (tg/—) rats, when fed ad libitum (Figure 31.5C). Levels were also increased in (—/—)-CR rats. In addition, CR of (tg/—) rats additively increased plasma adiponectin concentrations. The increased concentration with CR was slightly greater in (tg/—) rats.
This increased adiponectin concentration might be linked to the increased sensitivity of insulin or lower concentration of plasma insulin after glucose load. Recent studies have indicated that adiponectin could facilitate glucose uptake into skeletal muscle and adipocytes independent of insulin action, through activation of AMP-activated protein kinase (AMPK) (Tomas et al., 2002; Wu et al., 2003). The adiponectin-AMPK pathway might act as the insulin-independent pathway for glucose metabolism in long-lived dwarf and CR animals. The level of phosphorylated AMPK, the active form of the enzyme, is increased in GHRKO mice (Al-Regaiey et al., 2005),
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