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KNDy neurons co-expressing kisspeptin (KP), neurokinin B (NKB) and dynorphin A (DYN A) in the arcuate nucleus of the hypothalamus (ARC) are key regulators of reproduction. Their activity is influenced by metabolic and hormonal signals. Previously, we have shown that orchidectomy alters the KP-, NKB-, and DYN A-immunoreactivity in the high-fat diet-induced (HFD) obesity and diabetes type 2 (DM2) models. Considering the potential sex difference in the response of KNDy neurons, we have hypothesized that ovariectomy (OVX) and post-ovariectomy replacement with estradiol (OVX+E 2 ) or estradiol and progesterone (OVX+E 2 +P 4 ) will also affect these neurons in HFD and DM2 females. Thus, each of these treatment protocols were employed for control, HFD, and DM2 groups of rats leading to nine experimental conditions within which we have determined the number of KP-, NKB-, or DYN-immunoreactive (-ir) neurons and assessed the metabolic and hormonal profiles of the animals. Accordingly: (1) no effects of group and surgery were observed on the number of KP-ir neurons; (2) the overall number of NKB-ir neurons was higher in the OVX+E 2 +P 4 and OVX+E 2 animals compared to OVX; (3) overall, the number of DYN A-ir neurons was higher in DM2 vs. control group, and surgery had an effect on the number of DYN A-ir neurons; (4) the metabolic and hormonal profiles were altered in HFD and DM2 animals compared to controls. Current data together with our previously published results indicate sex-specific differences in the response of KNDy neurons to DM2., (Copyright © 2020 IBRO. Published by Elsevier Ltd. All rights reserved.)

Obesity, which reaches an epidemic, is characterized by alterations in metabolic and hormonal profiles. Moreover, uncontrolled obesity may lead to development of diabetes type 2, which accounts for about 90% of all diabetic cases. In obesity, besides changes in metabolism, numerous co-morbidities are reported, e.g. disruptions of reproductive functions. Additionally, sex differences in development of this disease occur. We hypothesized that short-term exposure to high-fat diet (HFD; containing 50% of total energy from fat) would alter histology of testes and ovaries, and thus contribute to reproductive disruptions in male and female rats. Adult rats were fed ad libitum with HFD for 6-7 weeks and its effects on histology of testes and ovaries (n = 4/sex and treatment group) were studied using hematoxylin-eosin staining followed by microscopic analysis and compared to control (laboratory chow fed) group. We have found that in male rats fed with HFD there were: 1) decrease in diameter of seminiferous tubules due to smaller luminar diameter, and no change in epithelium height; 2) decrease in number of Sertoli cells; 3) no changes in number of spermatogonia and in percentage of semen in seminiferous tubules. In female rats exposed to HFD we have seen: 1) decrease in diameters of corpora lutea; 2) decrease in diameter of ovarian follicles types 7 and 8, but no changes in their number; 3) no changes in number of early primary follicles, primary follicles, and secondary follicles. We concluded that relatively short-term exposure to HFD in rats leads to changes in histology of both testes and ovaries, thus affecting reproductive functions., Competing Interests: Declaration of Competing Interest All authors declare no conflict of interest., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Apart from the primary metabolic symptoms of obesity and/or diabetes, there are numerous secondary problems, including disruptions of the reproductive system. The KNDy neurones, which express kisspeptin, neurokinin B and dynorphin A and are located in the arcuate nucleus of the hypothalamus (ARC), are important regulators of reproduction. Their functions are highly influenced by metabolic and hormonal status. We have previously shown that, in male rats with experimentally-induced diabetes type 2 (but not with high-fat diet-induced obesity), there are alterations in the number of these cells. In the present study, we hypothesised that a high-fat diet (HFD) and/or diabetes type 2 (DM2) in female rats affect the oestrous cycle, hormonal profiles and the number of kisspeptin-immunoreactive, neurokinin B-immunoreactive and/or dynorphin A-immunoreactive neurones in the ARC. Rats were assigned to one of three groups: a control group fed a regular chow diet, a high-fat diet group (HFD) and a diabetic group (DM2), with both of the latter two groups receiving a high calorie diet (50% of energy from lard). The third group was additionally treated with streptozotocin to induce DM2. Their oestrous cycles was monitored and their metabolic and hormonal status were assessed. We found that HFD and DM2 female rats, despite having significant alterations in their metabolic and hormonal profiles, as well as disruptions of the oestrous cycle, showed no changes in the number of the kisspeptin-immunoreactive, neurokinin B-immunoreactive and/or dynorphin A-immunoreactive neurones in the ARC. However, slight differences in the rostrocaudal distribution of these neurones among groups were reported. In conclusion, the data from the present study, together with our previously published results in males, indicate sex differences in the response of KNDy neurones to DM2 but not to HFD conditions., (© 2018 British Society for Neuroendocrinology.)