Increased plasma IGF-1 levels but lack of changes in adipocyte glucose transport in weanling rats with dorsomedial hypothalamic nucleus lesions 1 year after lesion production

Abstract

Experimental destruction of the dorsomedial hypothalamic nuclei (DMN) in weanling rats exerts an antiaging effect by preventing microalbuminuria and kidney lesions both 1 month and 1 year after lesion production. In the present study we report further on antiaging effects of DMN lesions (DMNL) by measuring glucose transport into adipocytes and plasma levels of insulin-like growth factors 1 and 2 (IGF-I, IGF-II). Male and female weanling Sprague-Dawley rats received bilateral electrolytic lesions in the DMN; sham-operated animals served as controls (SCON). The rats were maintained for 1 year and food intake was measured 3 weeks after surgery and 3 weeks prior to sacrifice. As expected, DMNL resulted in profound reductions of body weight and food intake, with male DMNL rats showing higher body weights and body weight gains than their female counterparts. The same was true of the respective SCON. In male DMNL rats, carcass fat in absolute terms was significantly reduced vs. SCON, but it was comparable among all groups when expressed in percent. Lean body mass (LBM), although significantly reduced in absolute terms in DMNL rats vs. SCON, was, however, significantly higher in male DMNL vs. SCON when expressed in percent, but not in females. LBM laid down per food energy taken in was higher in DMNL rats of both sexes than in their respective SCON. Efficiency of food utilization was normal in male DMNL vs. male SCON but was higher in female DMNL vs. SCON. Both male and female DMNL rats had significantly higher plasma IGF-1 concentrations than their respective SCON, and male DMNL rats had higher values than female DMNL rats. Plasma concentrations of IGF-II were significantly higher in DMNL vs. SCON, but only in females. Under both basal and insulin-stimulated conditions, DMNL rats had normal 3-0-methylglucose flux in adipocytes from epididymal fat pads vs. SCON. However, DMNL and SCON responded similarly to the stimulating effect of insulin. Although one-year-old rats may not be considered “aged”, we do consider the observed lack of a drop in plasma IGF-1 levels that occurs with aging as an “anti-aging” effect of DMN lesions.