Perfluorooctane sulfonate (PFOS) is a degradation product of sulfonyl-based fluorochemicals that are used extensively in industrial and household applications. Humans and wildlife are exposed to this class of compounds from several sources. Toxicity tests in rodents have raised concerns about potential developmental, reproductive, and systemic effects of PFOS. However, the effect of PFOS on the neuroendocrine system has not been investigated thus far. In this study, adult female rats were injected intraperitoneally with 0, 1, or 10 mg PFOS/kg body weight (BW) for 2 weeks. Food and water intake, BW, and estrous cycles were monitored daily. At the end of treatment, PFOS levels in tissues were measured by high-performance liquid chromatography (HPLC) interfaced with electrospray mass spectrometry. Changes in brain monoamines were measured by HPLC with electrochemical detection, and serum corticosterone and leptin were monitored using radioimmunoassay. Treatment with PFOS produced a dose-dependent accumulation of this chemical in various body tissues, including the brain. PFOS exposure decreased food intake and BW in a dose-dependent manner. Treatment with PFOS affected estrous cyclicity and increased serum corticosterone levels while decreasing serum leptin concentrations. PFOS treatment also increased norepinephrine concentrations in the paraventricular nucleus of the hypothalamus. These results indicate that exposure to PFOS can affect the neuroendocrine system in rats.

Obesity. 2006;14:1905-1913. Objective: Human adenovirus 36 (Ad-36) increases adiposity and reduces serum lipids in chicken, mouse, and nonhuman primate models, and it is linked to obesity in seroepidemiological studies in humans. Involvement of the central nervous system (CNS) or adipose tissue in the mechanism of Ad-36-induced adiposity is unknown. The effects of Ad-36 on adiposity and on the neuroendocrine system were investigated in a rat model. Research Methods and Procedures: Five-week-old male Wistar rats were inoculated intraperitoneally with Ad-36 or medium. Results: Despite similar food intakes, infected rats attained significantly greater body weight and fat pad weight by 30 weeks post-inoculation. Epididymal-inguinal, retroperitoneal, and visceral fat pad weights of the infected group were greater by 60%, 46%, and 86%, respectively (p Ͻ 0.00001). The fasting serum insulin level and homeostasis model assessment index indicated greater insulin sensitivity in the infected group. Visceral adipose tissue expression of glycerol 3-phosphate dehydrogenase, peroxisome proliferatoractivated receptor ␥, and CCAAT/enhancer-binding protein ␣ and ␤ was markedly increased in the infected animals compared with controls. Ad-36 decreased norepinephrine levels significantly in the paraventricular nucleus in infected vs. control rats (mean Ϯ standard error, 8.9 Ϯ 1.1 vs. 12.8 Ϯ 1.2 pg/g protein; p Ͻ 0.05). Ad-36 markedly decreased serum corticosterone in infected vs. control rats (mean Ϯ standard error, 97 Ϯ 41.0 vs. 221 Ϯ 111 ng/mL; p Ͻ 0.005). Discussion: The results suggest that the pro-adipogenic effect of Ad-36 may involve peripheral as well as central effects. The male Wistar rat is a good model for the elucidation of metabolic and molecular mechanisms of Ad-36-induced adiposity.

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Objective: Consumption of a high-fat (HF) diet is a contributing factor for the development of obesity. HF diet per se acts as a stressor, stimulating hypothalamo-pituitary-adrenal (HPA) axis activity resulting in elevated glucocorticoid levels; however, the mechanism behind this activation is unclear. We hypothesized that consumption of an HF diet activates HPA axis by increasing norepinephrine (NE) in the paraventricular nucleus (PVN) of the hypothalamus, leading to elevation in corticotrophin-releasing hormone (CRH) concentration in the median eminence (ME) resulting in elevated serum corticosterone (CORT). Subjects: To test this hypothesis, diet-induced obese (DIO) and diet-resistant (DR) rats were exposed to either chow or HF diet for 6 weeks. Measurements: At the end of 6 weeks, NE in the PVN was measured using HPLC, CRH in the ME, and CORT and leptin levels in the serum were measured using RIA and ELISA, respectively. The gene expression of tyrosine hydroxylase (TH), the rate-limiting enzyme in NE synthesis, and leptin receptor in brainstem noradrenergic nuclei were also measured. Results: HF diet increased PVN NE in both DIO and DR rats (Po0.05). However, this was accompanied by increases in CRH and CORT secretion only in DR animals, but not in DIO rats. Leptin receptor mRNA levels in the brainstem noradrenergic areas were not affected in both DIO and DR rats. However, HF diet increased TH mRNA levels only in DIO rats. Conclusion: Significant differences occur in all the arms of HPA axis function between DIO and DR rats. Further studies are needed to determine whether this could be a causative factor or a consequence to obesity.

BACKGROUND Incidence of ovulatory disorders is common in obese animal models. The mechanism behind this effect is not clear. We hypothesized that high fat (HF) diet induces alterations in neuroendocrine mechanisms resulting in anovulation in diet-induced obese (DIO) animals. METHODS Adult female DIO and diet-resistant (DR) rats were fed either chow or HF diet (45% calories from fat) for 6 weeks. Oestrous cyclicity and body weight were monitored regularly. At the end of treatment, rats were implanted with a jugular catheter to monitor luteinising hormone (LH) levels on the day of prooestrous. Rats were sacrificed on the following prooestrous, their brains and ovaries were collected. Plasma from trunk blood was analyzed for oestradiol and leptin concentrations. Ovaries were fixed and sectioned for histological analysis. Brains were removed, frozen and sectioned and norepinephrine (NE) concentrations in discrete hypothalamic areas were measured using HPLC-EC. RESULTS HF diet affected oestrous cyclicity in both DIO and DR rats with the effect being more pronounced in DIO animals. HF diet increased leptin levels in both DIO and DR rats. Oestradiol levels were low in the DIO-HF group. NE levels in the hypothalamus were unaffected by HF diet or genotype. A normal LH surge was observed in DR-Chow rats and LH levels were low in the rest of the groups. CONCLUSION DIO rats have an inherently reduced reproductive capacity and exposure to a HF diet decreases it further. A reduction in oestradiol and LH surge levels could contribute to this effect, however the underlying mechanisms need to be studied further.