Daily Melatonin Administration at Middle Age Suppresses Male Rate Visceral Fat, Plasma Leptin, and Plasma Insulin to Youthful Levels

Abstract

Human and rat pineal melatonin secretion decline with aging, whereas visceral fat and plasma insulin levels increase. Melatonin modulates fat metabolism in some mammalian species, so these aging-associated melatonin, fat and insulin changes could be functionally related. Accordingly, we investigated the effects of daily melatonin supplementation to male Sprague-Dawley rats, starting at middle age (10 months) and continuing into old age (22 months). Melatonin was added to the drinking water (92% of which was consumed at night) at a dosage (4 microg/ml) previously reported to attenuate the aging-associated decrease in survival rate in male rats, as well as at a 10-fold lower dosage. The higher dosage produced nocturnal plasma melatonin levels in middle-aged rats which were 15-fold higher than in young (4 months) rats; nocturnal plasma melatonin levels in middle-aged rats receiving the lower dosage were not significantly different from young or middle-aged controls. Relative (% of body wt) retroperitoneal and epididymal fat, as well as plasma insulin and leptin levels, were all significantly increased at middle age when compared to young rats. All were restored within 10 weeks to youthful (4 month) levels in response to both dosages of melatonin. Continued treatment until old age maintained suppression of visceral (retroperitoneal + epididymal) fat levels. Plasma corticosterone and total thyroxine (T4) levels were not significantly altered by aging or melatonin treatment. Plasma testosterone, insulin-like growth factor I (IGF-I) and total triiodothyronine (T3) decreased by middle age; these aging-associated decreases were not significantly altered by melatonin treatment. Thus, visceral fat, insulin and leptin responses to melatonin administration may be independent of marked changes in gonadal, thyroid, adrenal or somatotropin regulation. Since increased visceral fat is associated with increased insulin resistance, diabetes, and cardiovascular disease, these results suggest that appropriate melatonin supplementation may potentially provide prophylaxis or therapy for some prominent pathologies associated with aging.

In vivo activation of insulin receptor tyrosine kinase by melatonin in the rat hypothalamus

“…The present report is the first to demonstrate that melatonin stimulates tyrosine phosphorylation of insulin receptor and IRS-1. These data suggest that IRS-1 phosphorylation may play a role as a converging target in insulin-and melatonin-stimulated signalling pathways and also as a probable link for both hormones in the control of body weight (Le Gouic et al 1996;Rasmussen et al 1999) and carbohydrate metabolism (Alquier et al 2003). The major lipid product of PI(3)K activity is phosphatidylinositol 3,4,5-triphosphate (PIP3).…”

Effects of 900MHz radiofrequency on corticosterone, emotional memory and neuroinflammation in middle-aged rats

“…Dawley and for IL in 12 month-old Fisher 344 rats and BALB/c mice (Gee et al, 2006;Kohman et al, 2010;Rasmussen et al, 1999). Deficits in Sprague Dawley and Wistar rats were reported later in the middle-age period (approximately 15 month-old), for micro and macroglia markers (CD11b, MHC II and GFAP) and IL levels, respectively (Bilbo, 2010;Hoane et al, 2004;Minogue et al, 2007).…”

Olanzapine-Induced Weight Gain and Increased Visceral Adiposity is Blocked by Melatonin Replacement Therapy in Rats

“…Because normal aging in humans and rats is associated with both increased visceral adiposity and decreased circulating melatonin concentrations (Grad and Rozencwaig, 1993), we previously investigated the effects of daily melatonin supplementation on aging-associated increased body weight and visceral fat in middle-aged rats. Melatonin treatment reduced body weight, and visceral fat was restored to youthful levels within 10 weeks (Rasmussen et al, 1999(Rasmussen et al, , 2001Wolden-Hanson et al, 2000). Continued melatonin supplementation until old age maintained suppression of this visceral fat accumulation (Rasmussen et al, 1999).…”

“…Melatonin treatment reduced body weight, and visceral fat was restored to youthful levels within 10 weeks (Rasmussen et al, 1999(Rasmussen et al, , 2001Wolden-Hanson et al, 2000). Continued melatonin supplementation until old age maintained suppression of this visceral fat accumulation (Rasmussen et al, 1999). We have now asked if olanzapine increases body weight and visceral adiposity in rats and, if so, whether melatonin replacement likewise reverses these changes.…”