Perfluorooctane sulfonate influences feeding behavior and gut motility via the hypothalamus

Abstract

Abstract. Perfluorinated compounds (PFCs) have been employed as surface treatment agents in a variety of products. Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are the two most commonly found PFCs in the environment and human blood. We investigated the effects of PFOS and PFOA on feeding behavior. PFOS or PFOA was administered intracerebroventricularly in mice or rats. Following administration, food intake, gastroduodenal motility, gastric emptying, gene expression of hypothalamic neuropeptides, and c-Fos expression along with immunoreaction for urocortin 2 in the paraventricular nucleus (PVN) were determined. Centrally administered PFOS and PFOA decreased food intake. Administration of PFOS decreased gastric emptying and disrupted the fasted motor activity in the antrum and duodenum. The gene expression of urocortin 2 in the hypothalamus and c-Fos expression and immunoreaction for urocortin 2 in the PVN were increased by the action of PFOS. A centrally administered corticotropin-releasing factor type 2 receptor (CRFR2) antagonist blocked PFOS-induced anorexia. These findings indicate that PFOS and PFOA influence feeding behavior. This effect is mediated via the activation of hypothalamic urocortin 2 and CRFR2, and the suppression of gastroduodenal motor activity. These observations indicate that PFCs may act centrally to influence behavior and physiological functions in humans.

Environmental and biological monitoring of persistent fluorinated compounds in Japan and their toxicities

“…Increased corticosterone concentrations in serum and norepinephrine in the hypothalamus were induced by PFOS in mice, indicating that PFOS stimulates the stress axis [93]. Observed decreases in food intake caused by PFOA and PFOS were mediated via the activation of hypothalamic urocortin 1 and 2, respectively [94,95]. PFOS exposure also induced behavioral effects in mice, such as anxiety and spatial memory loss [96].…”

“…Decreased birth weight [8,10] Early pregnancy loss, increased neonatal mortality, delayed eye opening, growth deficits, altered pubertal maturation [87,91] Behavioral and neurotoxicities Decreases in food consumption and body weight [85] Decreased food intake, reduced habituation and hyperactivity, hypoactive response to nicotine [94,96] Other Higher prevalence of angina, myocardial infarction, stroke, chronic bronchitis, shortness of breath on stairs, asthma [78] PFOS Carcinogenicity Bladder cancer mortality [9] Hepatocellular adenoma, thyroid follicular cell adenoma [80] Hepatotoxicities Possible increase in cholesterol, decrease in high-density cholesterol, initial decrease and subsequent increase in total bilirubin [76] Decreased body weights, increased liver weights, lowered serum total cholesterol levels, lowered estradiol levels, no peroxisome proliferation [86] Peroxisome proliferation, mild increase in hepatic palmitoyl CoA oxidase [80] Developmental toxicities Decreased birth weight, ponderal index, and head circumference [10] Increased relative liver weight of pups, delayed eye opening, neonatal death due to intracranial blood vessel dilatation and lung atelectasis, decreased natural killer cell function in male pups [88][89][90] Behavioral and neurotoxicities…”

Endocrine disrupters as obesogens

“…Depressed birth weight can be induced by low to moderate prenatal exposure (>5 mg/kg bw) of perfluorooctanoic acid (PFOA) in rodents [56,57] and an association between depressed birth weight and levels of PFOA in human umbilical cord blood has been documented [39]. PFOA probably exerts anorexigenic effects through a central hypothalamic mechanism that triggers a decrease in food intake in adult rodents [58]. This phenotype is not observed in PPARα knockout animals [59].…”

Historical Trends in Human Serum Levels of Perfluorooctanoate and Perfluorooctane Sulfonate in Shenyang, China

“…The mechanisms of their toxicities, other than in fatty acid metabolism, are not fully understood. PFOS might have an effect on the neuroendocrine system in rodents (Austin et al 2003;Asakawa et al 2007). PFOS and PFOA have electrophysiological effects on action potentials and currents (Harada et al 2005bMatsubara et al 2006).…”