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Autophagy is an evolutionarily conserved process that plays a crucial role in maintaining a series of cellular functions. It has been found that autophagy is closely involved in the physiological process of spermatogenesis and the regulation of sperm survival and motility. However, the role of autophagy in high-fat diet (HFD)-induced impaired spermatogenesis remains unknown. This study was designed to investigate the role of autophagy in HFD-induced spermatogenesis deficiency and employed chloroquine (CQ) to inhibit autophagy and rapamycin (RAP) to induce autophagy. 3-methyladenine (3-MA) and CQ were administered via intratesticular injection in vivo. The effects of CQ and 3-MA on the parameters of spermatozoa co-cultured with palmitic acid (PA) in vitro were also investigated. Human semen samples from obese, subfertile male patients were also collected to examine the level of autophagy. The results suggested that HFD mice subjected to CQ showed improved spermatogenesis. Inhibiting autophagy with CQ improved the decreased fertility of HFD male mice. Moreover, the in vivo and in vitro results indicated that both CQ and 3-MA could suppress the pathological changes in spermatozoa caused by HFD or PA treatment. Additionally, the excessive activation of autophagy was also observed in sperm samples from obese, subfertile male patients.

Purpose: The study aims to elucidate the changes in testicular spermatogenic function in high-fat diet (HFD)-induced obese rats and to evaluate the protective effects of metformin intervention., Methods: Male Sprague-Dawley rats (n = 18) were randomly divided into a control group (standard diet), an HFD group, and a metformin group (HFD + metformin at 100 mg/kg, once daily by oral gavage). After 8 weeks, rats were euthanized, and the weights of body and testes were measured. Testis and epididymis were dissected and hematoxylin-eosin-stained for histopathological examination and semen parameter analysis. Blood samples were collected for assessment of sex hormones and metabolic parameters (serum glucose, insulin, and leptin). Spermatogenic cell apoptosis was accessed by TUNEL., Results: Compared with the control group, the final body weight and weight gain were significantly higher in HFD rats, while the testicle weight and coefficients were lower. In HFD rats, metformin treatment induced weight loss and increased testicle weight (P < 0.05). In HFD rats, obvious pathological changes in the testicular tissue were characterized by small, atrophic, and distorted seminiferous tubules and destroyed basement membrane. Metformin treatment protected against the HFD-induced decrease in the number of spermatogonia, Sertoli cells, and Leydig cells (P < 0.05); ameliorated the HFD-induced increases in serum glucose, insulin, leptin, and estrogen; and decreased serum testosterone (P < 0.05) and reduced the rate of testicular cell apoptosis in obese male rats. Finally, metformin significantly improved semen parameters (including concentration, viability, motility, and normal morphology) in HFD rats (P < 0.05)., Conclusions: HFD-induced obesity in rats results in detrimental effects on spermatogenesis, semen quality, endogenous hormones, and testicular cell apoptosis. Metformin intervention improved the semen parameters, possibly due to its effects on weight loss, increased testicular weight, reduced testicular cell apoptosis, and resulted in restoration of hormonal homeostasis and correction of metabolic disorder.

Objective: To study the distribution characteristics of adiponectin gene +45 single nucleotide polymorphisms (SNP) in Chinese children, and to determine the role of adiponectin gene +45 polymorphisms in the pathogenesis of childhood obesity., Methods: A total of 147 Chinese obese and 118 healthy children were randomly selected and enrolled to identify adiponectin gene SNP+45 polymorphism by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Plasma adiponectin levels were determined using ELISA. Waist circumference (WC), waist to hip ratio (WHR), percentage of body fat (%BF), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting plasma glucose (FPG), serum triglycerides (TG), total cholesterol (TC), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), plasma fasting insulin (FINS), and homeostasis model assessment of insulin resistance (HOMA-IR) were measured., Results: The allelic frequency of adiponectin gene SNP+45 in children with obesity and healthy controls were 40.5% and 25.4%, respectively. There were significant differences in the distribution of genotypes and the allelic frequency between the two groups (P<0.05). The plasma adiponectin levels were significantly higher, in contrast, %BF, HOMA-IR, TC and LDL-C levels were significantly lower in obese children with TT genotype than those in obese children with TG or GG genotype., Conclusions: The adiponectin gene SNP+45 polymorphism may be associated with pathogenesis of obesity in children. T→G variance may be associated an increased risk of childhood obesity and result in a decreased level of adiponectin.

Objective: To examine plasma adiponectin (ADPN) and tumor necrosis factor-alpha (TNF-alpha) levels and their correlation in children with obesity in order to investigate the roles of both in the development of childhood obesity., Methods: One hundred and forty-seven children with obesity and 118 normal children who were randomly sampled from five primary schools from the Kaifu District in Changsha were enrolled. Physical shape indexes, including height, weight, waist circumference, hip circumference, and waist to hip ratio (WHR) were measured. Body mass index (BMI) was calculated. Blood pressure was measured. Percentage of body fat (%BF) was measured with dual energy X-ray absorptiometry. Plasmal levels of ADPN and TNF-alpha were detected using ABC-ELISA. Blood concentrations of triglycerides (TG), total cholesterol (TC), high density lipoprotein-cholesterol (HDL-C) and low density lipoprotein-cholesterol (LDL-C) were measured by automatic biochemistry analyzer. Fasting blood glucose level was measured by glucose oxidase method. Fasting blood insulin level was assayed by radioimmunity. Homeostasis model assessment for insulin resistance (HOMA-IR) was performed., Results: Plasma ADPN levels in obese children significantly decreased compared with those in normal children (8.12+/-2.54 mg/L vs 12.22+/-4.68 mg/L; p<0.05), and had a negative correlation with plasma TNF-alpha levels, BMI, WHR and HOMA-IR (p<0.01), and with %BF, fasting insulin, systolic blood pressure and TG (p<0.05). Plasma TNF-alpha levels in obese children significantly increased compared to normal children (171.38+/-34.33 ng/L vs 91.07+/-21.60 ng/L; p<0.01) and positively correlated with BMI, WHR, %BF, fasting insulin, HOMA-IR, TG and systolic blood pressure (p<0.01), and negatively with HDL (p<0.05). Multiple stepwise regression analysis showed that ADPN, BMI and TNF-alpha were main influential factors for %BF (R2=0.926, p<0.01). There was a significant interaction between ADPN and TNF-alpha (p<0.05)., Conclusions: Plasma ADPN levels decreased and plasma TNF-alpha levels increased in children with obesity and both were main influential factors for %BF in children. There was an interaction between ADPN and TNF-alpha, suggesting that they both participate in the development of childhood obesity.