| Calorie restriction (CR) is one of the most effective treatments to reduce body fat and improve insulin sensitivity. Ames dwarf (df/df) mice are long-lived and insulin sensitive, whereas growth hormone (GH) overexpressing transgenic (Tg) mice are short-lived and insulin resistant. In order to address the mechanisms of altered insulin sensitivity in these mice, as well as the effects of CR on adipose signaling and metabolism, we fed df/df and transgenic mice ad libitum (AL) or subjected them to 30% CR. We then assayed plasma adipocytokines related to insulin sensitivity, plasma lipids and tissue triglycerides, and adipocytes morphology. Furthermore, we evaluated mRNA expression and protein levels of enzymes or regulators involved in regulating hepatic lipid metabolism. Our results suggest that enhanced insulin sensitivity in df/df mice may be partly due to increased release of adiponectin and the reduced release of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). Altered levels of adipocytokines might be consequent to the decreased lipid synthesis, plasma triglycerides, and free fatty acid levels df/df mice. In normal mice, CR improves insulin sensitivity by affecting the release of adipocytokines and decreasing circulating fatty acid and triglycerides as well as liver triglyceride. In Tg mice, decreased plasma adiponectin, increased resistin and cholesterol, as well as elevated TNF-alpha and IL-6 in adipocytes might contribute to the insulin resistance. Increased triglycerides and impaired adipocyte differentiation in Tg mice might contribute to the alteration of adipocytokines. Hepatic insulin resistance in these mice is probably due to the excess accumulation of fatty acids and their metabolites. CR may improve insulin sensitivity by enhancing the release of plasma adiponectin and decreasing IL-6, triglycerides and cholesterol. In conclusion, our results suggest that alterations in adipocytokines and lipid, as well as lipid contents in insulin-target tissues, which might be due to the changes of enzymes or regulators involved in lipid metabolism, are closely linked to altered insulin sensitivity in df/df and GH-Tg mice. CR may improve insulin sensitivity by affecting the release of adipocytokines and lipid levels, the lipid accumulation in white adipose tissue (WAT) or liver, as well as changing the size of adipocytes. |
