Background: The incidence of male reproductive dysfunction is increasing annually, and many studies have shown that obesity can cause severe harm to male reproductive function. The mechanism of male reproductive dysfunction caused by obesity is unclear, and there is no ideal treatment. Identification of effective therapeutic drugs and elucidation of the molecular mechanism involved in male reproductive health are meaningful. In this study, we investigated the effects of the GLP-1 receptor agonist liraglutide on sex hormones, semen quality, and testicular AC3/cAMP/PKA levels in high-fat-diet-induced obese mice. Methods: Obese mice and their lean littermates were treated with liraglutide or saline for 12 weeks. Body weight was measured weekly. Fasting blood glucose (FBG) was measured using a blood glucose test strip. The serum levels of insulin (INS), luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone (T), free testosterone (F-TESTO), estradiol (E2), and sex hormone binding globulin (SHBG) were detected using ELISA. The sperm morphology and sperm count were observed after Pap staining. The mRNA and protein expression levels of testicular GLP-1R and AC3 were measured by RT-qPCR and Western blot, respectively. Testicular cAMP levels and PKA activity were detected using ELISA. Results: Liraglutide treatment can decrease body weight, FBG, INS, HOMA-IR, E2 and SHBG levels; increase LH, FSH, T, and F-TESTO levels; increase sperm count; decrease the sperm abnormality rate; and increase GLP-1R and AC3 expression levels and cAMP levels and PKA activity in testicular tissue. Conclusions: Liraglutide can improve the sex hormone levels and semen quality of obese male mice. In addition to its weight loss effect, liraglutide can improve the reproductive function of obese male mice, which may also be related to the upregulation of AC3/cAMP/PKA pathway in the testis. This work lays the groundwork for future clinical studies.

Objective: This study aims to investigate the relationship between the triglyceride-glucose (TyG) index and the triglyceride-glucose-body mass (TyG-BMI) index and the severity of hepatic steatosis and liver fibrosis in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), providing more accurate metabolic indicators for non-invasive screening. Methods: A retrospective analysis was conducted on 7,035 subjects who completed Fibrotouch testing. Multivariate logistic regression analysis was used to assess the correlation between the TyG index and TyG-BMI index and the severity of hepatic steatosis (mild, moderate, severe) and hepatic fibrosis. Quartile grouping analysis and ROC curve assessment were also used to evaluate predictive performance. Results: After adjusting for potential confounding factors, both the TyG index and the TyG-BMI index were significantly positively correlated with the severity of MASLD (both p < 0.001). The association was stronger for TyG-BMI, with the highest quartile (Q4) having a 239.41-fold higher risk of hepatic steatosis compared to the lowest quartile (Q1; OR = 239.41, 95% CI: 170.99–335.21). For liver fibrosis, only TyG-BMI maintained independent association (OR = 1.029, 95% CI: 1.025–1.033). ROC analysis showed that TyG-BMI had significantly better predictive performance for MASLD than TyG (AUC: 0.908 vs. 0.774). Conclusions: The TyG-BMI index is a strong predictor of MASLD severity and liver fibrosis, with predictive performance superior to that of the traditional TyG index. It can serve as an effective tool for clinical screening of high-risk populations for MASLD.

Objective: To explore the relationship between controlled attenuation parameters (CAP) of the liver and the risk of type 2 diabetes mellitus (T2DM), and to determine the optimal cutoff value of CAP for predicting T2DM. Methods: This study employed a cross-sectional study design, enrolling 7035 participants. CAP values were measured using hepatic transient elastography, and participants were categorized into low (≤ 231 dB/m), middle (232~269 dB/m), and high (≥ 270 dB/m) groups. Multivariate logistic regression analysis was used to assess the association between CAP and T2DM, and the optimal cutoff value was determined using receiver operating characteristic (ROC) curves. Results: After adjusting for potential confounders, participants in the high-CAP group had a significantly greater risk of developing T2DM than did those in the low-CAP group (OR=1.545; 95% CI=1.263– 1.890; p< 0.001). Stratified analyses revealed that compared with a low CAP, a 1.0-increased CAP was associated with a 0.852-fold increased T2DM risk in people aged < 55 years (OR=1.852; 95% CI=1.405– 2.441; p< 0.001) and a 0.6-fold increased T2DM risk in overweight patients (BMI≥ 24 kg/m2) (OR=1.600; 95% CI=1.127– 2.271; p=0.009). ROC analysis revealed an optimal CAP cutoff value of 246.5 dB/m for T2DM prediction, with an area under the curve of 0.569 (specificity=48.2%, sensitivity=64.2%). Conclusion: CAP levels are associated with a dose-response relationship with the risk of T2DM, particularly in younger and overweight populations. Although CAP has limited predictive value on its own, it can be used as an auxiliary indicator for T2DM risk screening.