Divergent regulation of adipose tissue metabolism by calorie restriction and inhibition of growth hormone signaling.

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Calorie restriction (CR) and a reduced growth hormone (GH) signal affect insulin sensitivity and lifespan in mammals in a similar manner. We investigated the effects of CR and moderate inhibition of GH on glucose-stimulated activation of insulin signaling and the expression of genes related to fat metabolism in white adipose tissue (WAT) in rats. We used 10-month-old male, wild-type (W) Wistar rats, fed ad libitum (AL) or a 30% CR diet from 6weeks of age, and transgenic (Tg) rats with moderately suppressed GH signaling. Rats were killed 15min after an intraperitoneal injection of glucose or saline. In control W-AL rats, the levels of serum insulin, phosphorylated (p) insulin receptor (pY-IR), p-Akt, and the expression of glucose transporter (Glut) 4 in the membrane fraction were greater in the glucose-injected group than in the saline-injected group, indicating significant activation of insulin signaling in response to glucose loading. In the W-CR and Tg-AL rats, the serum insulin and pY-IR levels were lower than those in the W-AL rats. The Akt-Glut pathway was up-regulated even after saline-injection. Expression levels of adipogenic and lipogenic genes including PPARgamma, adiponectin, and its receptors, were higher in the W-CR rats than in the W-AL and Tg-AL rats. The present findings indicate adipose tissue metabolic profiles specific to CR.