Effect of immune stress on body weight regulation is altered by ovariectomy in female rats.

It has been suggested that obesity and loss of ovarian function alter the inflammatory response to immune stress. Ovariectomized (OVX) rats, which are used as a model of human menopause, exhibit both hyperphagia-induced obesity and gonadal steroid deficiency. To evaluate the effects of ovariectomy on inflammatory responses, we compared the anorectic response to LPS in OVX rats and gonad intact female rats. As leptin and hypothalamic interleukin-1ß (IL1ß) play pivotal roles in the anorectic response to immune stress, these factors were also measured. It was found that the OVX rats exhibited an increased anorectic response to LPS compared with the sham-operated rats. The OVX rats showed higher serum leptin concentrations and a greater increase in hypothalamic IL1ß mRNA expression after LPS injection. In addition, in order to determine whether gonadal steroid deficiency contributes to the changes in the inflammatory responses of OVX rats, we compared responses between OVX rats treated with gonadal steroids and untreated OVX rats. There were no differences in appetite, the serum leptin level, and hypothalamic IL1ß mRNA expression between the two groups after LPS injection. These findings suggest that the loss of ovarian function increases the induction of leptin and hypothalamic IL1ß synthesis and consequently increases the anorectic response under immune stress conditions. It is possible that these alterations are caused by OVX-induced obesity rather than the direct effects of gonadal steroid deficiency.

Sensitivities of mRNA expression levels of Kiss1 and its receptor, Kiss1r, to nutritional status are changed during the developmental period in female rats.

Decreased activity of kisspeptin, the product of the hypothalamic Kiss1 gene, is the major cause of the suppression of reproductive function in subnutritional conditions. The sensitivities of the endocrine and the hypothalamic neuronal systems to nutritional status develop during the neonatal period. We examined the developmental changes in the sensitivity of hypothalamic mRNA expression of Kiss1 and its receptor, Kiss1r, to nutritional status in female rats. Kiss1 mRNA expression was reduced by 24 h food deprivation (24 h FD) at postnatal day 25, but not at postnatal day 5 or 15. Kiss1r mRNA expression was reduced by the 12 or 24 h FD at postnatal days 5 and 25, but not at postnatal day 15. Kiss1r mRNA level was found to be correlated with the plasma leptin level, and the administration of leptin, which increased the serum leptin concentration above the physiological range, restored the acute FD-induced suppression of Kiss1r mRNA expression. These data suggest that the hypothalamic Kiss1 and Kiss1r mRNA expression is differentially affected by the nutritional condition at different age points. It is speculated that the sensitivity of Kiss1 mRNA, which is expressed in kisspeptin neuron, to nutritional status develops during the neonatal period. On the other hand, it seems that the sensitivity of Kiss1r mRNA, which is expressed in GnRH neuron, to nutritional status has been already established during the early neonatal period. These data also show that hypoleptinemia plays a role in the reduction of hypothalamic Kiss1r mRNA expression under subnutritional conditions.

Neonatal LPS injection alters the body weight regulation systems of rats under non-stress and immune stress conditions.

It has been reported that prenatal immune stress induced by lipopolysaccharides or cytokines increases food intake and leads to obesity and other features of metabolic syndrome in adulthood. Using Sprague-Dawley rats, we evaluated whether neonatal LPS injection altered their body weight regulation systems under non-stress and immune stress conditions. On Day 10 after birth, all pups were injected with LPS (100 microg/kg, i.p.) (PND(10)LPS) or saline (PND(10)Saline). After weaning, body weight was significantly elevated in PND(10)LPS compared with PND(10)Saline. Thereafter, the rats were injected with LPS (100 microg/kg, i.p.) or saline (used as a basal condition) from 7 to 8 weeks of age. Under basal conditions, cumulative food intake were significantly higher, serum leptin concentration was significantly increased, and hypothalamic NPY mRNA expression was significantly decreased in PND(10)LPS compared with PND(10)Saline. Under adult LPS injected conditions, body weight gain and cumulative food intake were suppressed in both the PND(10)LPS and PND(10)Saline groups compared with those observed under basal adult saline-injected conditions. The suppressive effects induced by adult LPS injection were less evident in the PND(10)LPS group than in the PND(10)Saline group. Adult LPS injection increased the serum leptin concentration in the PND(10)Saline rats, but not in the PND(10)LPS rats. In addition, adult LPS injection increased the mRNA expression of anorexinergic factors (IL-1beta, and TNF-alpha), and decreased that of the orexinergic factor NPY in both groups. However, the influence of adult LPS injection upon these factors was less evident in the PND(10)LPS group than in the PND(10)Saline group. These results suggest that neonatal LPS injection alters body weight regulation under both non-stress and immune stress conditions in male rats. Changes in the endocrine, neuropeptide, and cytokine regulation systems might be involved in these alterations.