Attenuation of leptin-mediated effects by monosodium glutamate-induced arcuate nucleus damage

Abstract

Leptin is a protein secreted by adipocytes that is important in regulating appetite and adiposity. Recent studies have suggested the presence of leptin receptors in the arcuate nucleus of the hypothalamus (ANH). Neonatal administration of monosodium glutamate (MSG) damages the ANH, resulting in obesity and neuroendocrine dysfunction. Neonatal administration of MSG was utilized to test the hypothesis that the anatomic site for many of leptin's actions is the ANH. Female control (n = 6) and MSG-treated rats (n = 7) were implanted for 14 days with osmotic minipumps containing phosphate-buffered saline or leptin (1 mg.kg-1.day-1). Leptin suppressed (P < 0.05) body weight gain in controls but did not suppress weight gain in MSG-treated rats. Leptin decreased (P < 0.05) fat depots in controls but had no effect in MSG-treated rats. Night feeding was suppressed (P < 0.05) in leptin-treated control rats. MSG-treated rats showed a suppression in food intake that was of a smaller magnitude and appeared later in the course of leptin treatment. These findings suggest that leptin mediates some physiological actions related to fat mobilization via receptors located in the ANH.

Avaliação do crescimento corporal e dos neurônios mioentéricos de ratos Wistar após tratamento neonatal com glutamato monossódico

“…The testes of the rats from group MSG had caloric density lower than those from group C. MSG animals have hypotrophy of gonads, prostate and pituitary (Pizzi and Barnhart, 1976;Pizzi et al, 1979;Hamaoka and Kusunoki, 1986;Miskowiak and Partyka, 1993). Low levels of gonadotrophic and gonadal hormones were also reported (Nemeroff et al, 1981;Gong et al, 1995;Franca et al, 2006). Therefore, the results of this study combine with those on the literature pointing to a reduced reproductive capacity of the MSG animals, which was confirmed in some investigations (Bakke et al, 1978;Nemeroff et al, 1981;Gong et al, 1995;Franca et al, 2006).…”

“…On the other hand, the accumulation of adipose tissue in group MSG, given by the greater relative weight of the retroperitoneal and periepididymal fats, confirms that the treatment caused obesity. The greater efficiency in the storage of nutrients as fat was ascribed both to the autonomic impairment and the disturbance of the hypothalamic actions of leptin due to the ARC lesion caused by MSG (Bray, 1984;Dawson et al, 1997;Martins et al, 2004). Other changes which disturb glucose homeostasis, such as hyperinsulinemia, insulin resistance and imbalances of glucocorticoid activity (Sartin et al, 1985;Yamamoto et al, 1993;Hirata et al, 1997;Macho et al, 2000), must also be involved.…”

“…Maringá, v. 29, n. 1, p. 87-94, 2007 the ARC, with fibers projecting to the median eminence (Olney, 1969). The neonatal treatment with MSG results in selective destruction of these neurons, and this neuronal damage affects an area closely linked to the regulation of different functions, such as energy balance and functioning of the hypothalamus-pituitary and hypothalamusadipose tissue axes (Bakke et al, 1978;Dolnikoff et al, 1988;Remke et al, 1988;Dawson et al, 1997). It can be suspected that the hormonal/metabolic alterations resulting from the neonatal treatment with MSG determined a change on the body protein/fat ratio, resulting in rats of smaller body weight and greater fat content.…”

“…The orexins form another group of neuropeptides whose involvement in feeding behavior has been recently emphasized. The orexin-secreting neurons have wide projections in the brain, and are in turn influenced by the ARC neurons, including those secreting neuropeptide Y. Leptin, a hormone produced by the adipose tissue, is one of the modulators of this pathway (Dawson et al, 1997;Sakurai, 1999). The regulation of all visceral function is carried out by the ANS.…”

“…When adults, these animals show, in addition to obesity, several endocrine changes (Bakke et al, 1978;Nemeroff et al, 1981;Dolnikoff et al, 1988;Gong et al, 1995;Macho et al, 2000;Franca et al, 2006) and autonomic alterations (Bray, 1984;Yoshida et al, 1984;Sartin et al, 1985;Leigh et al, 1992;Martins et al, 2004).…”