leptin and Rodent-Diseases

Mammalian spermatogenesis is a temperature-sensitive process, and an increase in testicular temperature impairs spermatogenesis. Leptin modulates testicular activity, but the effect of leptin or its synthetic analogue on heat-induced testicular impairment is unclear. We investigated the effects of synthetic leptin peptide (116-130 amides) on testicular activity in heat-stressed mice model. 15 adult mice (25.54 ± 1.43 g) were selected for the study. Ten mice were subjected to a single heat stress treatment (HS) at 43 °C for 15 min by submerging the lower half of the body in a thermostatic water bath. After heat treatment, mice were divided into two groups, the heat-stressed HS group (n = 5) and the second group as HSL, treated with leptin peptide (116-130 amide) for 14 days. The HS group showed a significant (p < 0.05) decline in the GSI (0.25 ± 0.018), Johnsenscore (4.5 ±.19), seminiferous tubule diameter (160.75 ± 10.18 μm), germinal epithelium height, (GEH) (37.5 ± 1.59 μm) compared to the CN (GSI-0.37 ± 0.015; Johnsen score-7.9 ± 0.20; GEH- 73.25 ± 1.29 μm; tubule diameter-230.25 ± 1.39 μm) and the HSL groups (GSI-0.38 ± 0.014; Johnsen' score-8.0 ± 0.32; GEH- 37.5 ± 1.59 μm; tubule diameter-160.75 ± 10.18 μm) groups. Heat treatment significantly (p < 0.05) increased the intra-testicular levels of leptin (HS-20.11 ± 2.1 pg/mg protein; CN-10.50 ± 0.17 pg/mg protein; HSL-12.99 ± 0.52 pg/mg protein) with a reduced level of pStat3, suggesting leptin resistance during testicular hyperthermia. Furthermore, heat treatment was associated with significantly (p < 0.05) decreased germ cell proliferation and reduced circulating testosterone levels (HS-2.69 ± 2.01 ng/mL; CN-7.69 ± 0.32 ng/mL; HSL-5.36 ± 0.73 ng/mL). However, the circulating androstenedione levels showed a significant (p < 0.05) increase in the HS group (0.75 ± 0.03 ng/mL) compared to the CN (0.51 ± 0.02 ng/mL) and HSL (0.57 ± 0.07 ng/mL) groups. Immunolocalisation of 3β-HSD showed moderate to faint staining in the Leydig cells in the HS group compared to the CN and HSL groups. Treatment with leptin peptide resulted in decrease in the intra-testicular leptin levels with increased phosphorylation of Stat3, suggesting improved leptin resistance, which was positively associated with increased germ cell proliferation, elevated testosterone levels, and improved testicular histoarchitecture. Testicular hyperthermia may cause leptin resistance and impaired leptin signalling, decreased testosterone biosynthe

Topics: Animals; Heat Stress Disorders; Leptin; Leydig Cells; Male; Mice; Rodent Diseases; Spermatogenesis; Testis; Testosterone

A pregnant hamster's exposure to changes in environmental factors, such as light, temperature and nutrition, may influence behavioural and physiological changes in offspring. In this study, dietary methyl donor supplementation was employed to examine the role of maternal diet on appetite, body weight, serum leptin levels and locomotor activity in male Syrian hamster offspring. Dams were fed a standard control (SC) or methyl donor-supplemented (MDSD) diet through pregnancy and lactation. At birth, offspring were cross-fostered to dams fed an SC or MDSD diet (SC-MDSD and MDSD-SC) or remained with their birth mothers (SC-SC and MDSD-MDSD). At weaning, offspring were fed a SC or MDSD diet until 60 days of age. Food intake, serum leptin levels and locomotor activity were measured from 30-60 days of age. Offspring fed a MDSD diet post-weaning (MDSD-MDSD and SC-MDSD) consumed more than double the amount of food daily compared with offspring fed a SC diet post-weaning (SC-SC, MDSD-SC). Interestingly, there were no observed differences in body weight among all four groups. Serum leptin levels at 60 days of age were depressed in offspring fed a MDSD diet post-weaning (MDSD-MDSD and SC-MDSD). There were no observed differences in wheel running activity between the SC-SC and MDSC-SC groups. Wheel running activity was at least twice the amount in offspring fed a MDSD diet post-weaning (SC-MDSD and MDSD-MDSD). Taken together, these results indicate that the timing of methyl donor supplementation appears to be an important factor during the development of offspring.

Topics: Animals; Appetite; Body Weight; Cricetinae; Dietary Supplements; Female; Lactation; Leptin; Male; Maternal Nutritional Physiological Phenomena; Mesocricetus; Motor Activity; Pregnancy; Prenatal Exposure Delayed Effects; Rodent Diseases

Obesity leads to insulin resistance and is a major risk factor for the development of diabetes mellitus in cats. Prevention of obesity and obesity-induced insulin resistance is difficult, and reliable long-term strategies are currently lacking. Retinoid-related orphan receptor gamma (RORγ) was recently identified as an important transcription factor in the development of large insulin-resistant adipocytes in mice and humans. RORγ negatively affects adipocyte differentiation through expression of its target gene matrix metalloproteinase 3 (MMP3) and promotes the development of large insulin-resistant adipocytes. Preliminary studies in mice showed that RORγ can be inhibited by its ligand tetra-hydroxylated bile acid (THBA). In the present study, serum THBA levels were determined in healthy and diabetic cats. Moreover, potential side effects and the effects of THBA supplementation on adipocyte size, mRNA expression of RORγ, MMP3, interleukin 6, tumor necrosis factor α, adiponectin and leptin in feline subcutaneous adipocytes and insulin sensitivity were investigated in healthy normal weight cats. Thirteen healthy and 13 diabetic cats were used for determination of serum THBA level, and six healthy normal-weight cats were included in a feeding trial. Similar THBA levels were determined in serum of healthy and diabetic cats. Supplementation of 5 mg/kg THBA for 8 wk did not cause any negative effect on feeding behavior, general condition and blood parameters of tested cats. It significantly reduced adipocyte size and mRNA expression of MMP3, interleukin 6, and tumor necrosis factor α in adipocytes, while mRNA expression of adiponectin significantly increased and mRNA expression of RORγ and leptin remained unchanged. Administration of THBA did not influence fasting blood glucose levels or the response of cats to acute insulin administration. Based on these results, THBA is palatable and is considered safe for use in cats. It reduces expression of MMP3 and promotes the development of small adipocytes with increased expression of adiponectin and reduced expression of interleukin 6 and tumor necrosis factor α. Further studies are recommended to evaluate the effect of THBA on adipocyte size and insulin sensitivity in obese cats.

Topics: Adipocytes; Adiponectin; Animals; Bile Acids and Salts; Cat Diseases; Cats; Diabetes Mellitus; Insulin; Insulin Resistance; Interleukin-6; Leptin; Matrix Metalloproteinase 3; Mice; Obesity; RNA, Messenger; Rodent Diseases; Tumor Necrosis Factor-alpha