Selenium protects against nesfatin-1 modulation of the hypothalamic-pituitary-testicular axis during hypothyroidism in male rats.

Normal gonadal function can be disrupted by hypothyroidism. Hypothyroidism disturbs testicular function directly and centrally by affecting the hypothalamic-pituitary-testicular axis with unclear mechanism. As nesfatin-1 neurons co-localized with TRH and GnRH neurons in the hypothalamus, it could play a role in centrally hypothyroidism induced testicular dysfunction. Selenium (Se), by affecting thyroid iodide supply, could relieve these disturbances. So, we aim to identify the role of nesfatin-1 as a link between testicular dysfunction and hypothyroidism through modulating the MAPK/ERK pathway while discussing the possible role of Se in alleviating hypothyroidism and associated testicular damage. Forty male rats were divided equally into: Control: distilled water, Se: Se orally, Propylthiouracil (PTU): PTU orally, PTU + Se: Se with PTU orally. Serum thyroid function, gonadal hormones, nesfatin-1, testicular redox status, sperm analysis, brain tissue GnRH, nucleobindin 2-derived polypeptide, pMAPK/ERK gene expression, histological changes and immunohistochemical expression of testicular proliferating cell antigen (PCNA) were done. PTU induced hypothyroidism and reduction of gonadal hormones which both were correlated with reduced nesfatin-1. There was testicular stress with reduced GnRH, NUCB2, pMAPK/ERK gene expression, and PCNA immunopositive cells. These parameters were reversed by Se. Nesfatin-1 could be the central link between hypothyroidism and disturbances of the hypothalamic pituitary testicular axis.

Ameliorative effect of sesame oil on experimentally induced polycystic ovary syndrome: A cross-link between XBP-1/PPAR-1, regulatory proteins for lipogenesis/steroids.

Polycystic ovary syndrome (PCOS) is a mixed endocrine/metabolic/reproductive disorder in women of reproductive age. Sesame oil (SO) contains sesame lignans & vitamin E with broad-spectrum antioxidant and anti-inflammatory effects. This study investigates the ameliorative effect of SO on experimentally induced PCOS and elucidates the possible molecular mechanisms with a deeper focus on the different signaling pathways involved. The study was carried out on 28 nonpregnant female Wister albino rats that were divided into four equal groups; Group I (control group) received oral 0.5% wt/vol carboxymethyl cellulose daily. Group II (SO group): orally administered SO (2 mL/kg body wt./day) for 21 days. Group III (PCOS group) received letrozole daily, 1 mg/kg, for 21 days. Group IV (PCOS + SO group): concomitantly administered letrozole and SO for 21 days. The serum hormonal and metabolic panel and the homogenate ATF-1, StAR, MAPK, PKA, and PI3K levels of the ovarian tissue were calorimetrically evaluated. However, endoplasmic reticulum (ER) stress was evaluated by ovarian XBP1 and PPAR-γ messenger RNA expression level using the qRT-PCR technique. Ovarian COX-2 was detected immunohistochemically. The results suggest that SO-treated PCOS rats showed a significantly improved hormonal, metabolic panel, inflammatory, and ER stress status with concomitant decreases in ATF-1, StAR, MAPK, PKA, and PI3K in ovarian rats compared to the correspondent values in PCOS without treatment. CONCLUSIONS: The protective effects of SO against PCOS are triggered by ameliorating regulatory proteins of ER stress, lipogenesis, and steroidogenesis through the PI3K/PKA and MAPK/ERK2 signaling cascades. SIGNIFICANCE STATEMENT: Polycystic ovary syndrome (PCOS) is the most common mixed endocrine-metabolic dysfunction among women within the reproductive period, with an estimated prevalence of 5%-26% worldwide. Doctors traditionally recommend metformin for PCOS patients. However, metformin is known to be associated with significant adverse effects and contraindications. This work aimed at shedding light on the ameliorative effect of sesame oil (SO), natural polyunsaturated fatty acids-rich oil, on the induced PCOS model. SO proved to have a marvelous effect on the metabolic and endocrine derangements in the PCOS rat model. We hoped to provide a valuable alternative treatment for PCOS patients to avoid the side effects of metformin and to help PCOS patients for whom metformin is contraindicated.

Irisin improves adiposity and exercise tolerance in a rat model of postmenopausal obesity through enhancing adipo-myocyte thermogenesis

The prevalence of obesity and its associated metabolic disorders, along with their healthcare costs, is rising exponentially. Irisin, an adipomyokine, may serve as a critical cross-organ messenger, linking skeletal muscle with adipose tissue and the liver to integrate the energy homeostasis under diet-induced obesity. We aimed to explore the putative role of irisin in the protection against obesity in a postmenopausal rat model by modulating energy expenditure (EE). Bilateral ovariectomy (OVX) was performed. After 3 weeks of recovery, the OVX rats were classified according to their dietary protocol into rats maintained on normal diets (ND) (OVX) or high-fat diet (HFD) groups. The HFD-fed animals were equally divided into OVX/HFD, or irisin-treated OVX/HFD groups. Sham rats, maintained on ND, were selected as the control group. We evaluated anthropometric, EE, and molecular biomarkers of browning and thermogenesis in inguinal white adipose tissue and skeletal muscle, and the activity of the proteins related to mitochondrial long chain fatty acid transport, oxidation, and glycolysis. HFD of OVX further deteriorated the disturbed glucose homeostasis, lipid profile, and the reduced irisin, thermogenic parameters in adipose tissue and skeletal muscle, and EE. Irisin treatment improved the lipid profile and insulin resistance. That was associated with reduced hepatic gluconeogenic enzyme activities and restored hepatic glycogen content. Irisin reduced ectopic lipid infiltration. Irisin augmented EE by activating non-shivering thermogenesis in muscle and adipose tissues and decreasing metabolic efficiency. Our experimental evidence suggests irisin’s use as a potential thermogenic agent, therapeutically targeting obesity in postmenopausal patients. (AU)

Irisin improves adiposity and exercise tolerance in a rat model of postmenopausal obesity through enhancing adipo-myocyte thermogenesis.

The prevalence of obesity and its associated metabolic disorders, along with their healthcare costs, is rising exponentially. Irisin, an adipomyokine, may serve as a critical cross-organ messenger, linking skeletal muscle with adipose tissue and the liver to integrate the energy homeostasis under diet-induced obesity. We aimed to explore the putative role of irisin in the protection against obesity in a postmenopausal rat model by modulating energy expenditure (EE). Bilateral ovariectomy (OVX) was performed. After 3 weeks of recovery, the OVX rats were classified according to their dietary protocol into rats maintained on normal diets (ND) (OVX) or high-fat diet (HFD) groups. The HFD-fed animals were equally divided into OVX/HFD, or irisin-treated OVX/HFD groups. Sham rats, maintained on ND, were selected as the control group. We evaluated anthropometric, EE, and molecular biomarkers of browning and thermogenesis in inguinal white adipose tissue and skeletal muscle, and the activity of the proteins related to mitochondrial long chain fatty acid transport, oxidation, and glycolysis. HFD of OVX further deteriorated the disturbed glucose homeostasis, lipid profile, and the reduced irisin, thermogenic parameters in adipose tissue and skeletal muscle, and EE. Irisin treatment improved the lipid profile and insulin resistance. That was associated with reduced hepatic gluconeogenic enzyme activities and restored hepatic glycogen content. Irisin reduced ectopic lipid infiltration. Irisin augmented EE by activating non-shivering thermogenesis in muscle and adipose tissues and decreasing metabolic efficiency. Our experimental evidence suggests irisin's use as a potential thermogenic agent, therapeutically targeting obesity in postmenopausal patients. Irisin modulates the non-shivering thermogenesis in skeletal muscle and adipose tissue in postmenopausal model.