Nicotinamide mononucleotide (NMN), a precursor of nicotinamide adenine dinucleotide (NAD[+]), has been shown to improve oocyte quality in mammals. A healthy ovarian microenvironment is essential for oocyte quality and reproductive success in teleost fish. To investigate the effects of NMN on ovarian microenvironment parameters associated with oocyte quality in the spotted scat (Scatophagus argus), the levels of serum glucose, insulin, total cholesterol, triglycerides, 17β-estradiol (E2), and ovarian NAD[+] were analyzed following an intraperitoneal (IP) injection of NMN. Ovarian transcriptomic profiling was also conducted using RNA sequencing. The expression of genes related to steroidogenesis, apoptosis, and oxidative stress after NMN supplementation was analyzed by qRT-PCR. In vitro, ATP content, glutathione (GSH) levels, reactive oxygen species (ROS) accumulation, and mitochondrial membrane potential (ΔΨm) were quantified in follicles after NMN incubation. The results showed that NMN injection significantly increased ovarian NAD [+] levels and serum E2 concentrations. NMN improved glucose and lipid metabolism, as evidenced by elevated insulin levels and reduced serum glucose, total cholesterol, and triglycerides. KEGG enrichment analysis revealed significant enrichment of pathways related to metabolism, the stress response, and apoptosis. qRT-PCR demonstrated the upregulation of steroidogenesis-related genes (cyp17a1, hsd3b1, 20β-hsd, cyp19a1a, mmp2, and foxl2), antioxidant genes (gpx1a, gpx1b, and slc7a11), and the anti-apoptotic gene bcl2, along with downregulation of pro-apoptotic genes (bax and caspase3). NMN incubation reduced ROS accumulation and increased GSH levels, accompanied by enhanced mitochondrial function, as reflected by increased ΔΨm and ATP production. Collectively, these results suggest that NMN improves the ovarian microenvironment associated with oocyte quality in spotted scat by enhancing NAD[+] availability, which subsequently promotes estrogen signaling, reprogrammed ovarian metabolism, mitigates oxidative stress, and inhibits apoptosis.

Obesity is a major health concern, leading to diseases like diabetes, cardiovascular issues, and certain cancers, significantly reducing life quality and increasing mortality. While various treatments exist, new strategies are continuously explored. Polymethoxyflavones and their precursors, chalcones, are bioactive compounds with potential anti-obesity effects. This study investigated the therapeutic potential of methoxychalcone compounds in high-fat diet (HFD)-induced obese rats. We selected 1-(2,4,5-trimethoxyphenyl),3-(3,4,5-trimethoxyphenyl)prop-2-en-1-one for in vivo testing due to its low cytotoxicity and high in vitro lipase inhibitory activity. Obese rats received 10 mg/kg or 40 mg/kg body weight/day of the compound for 8 weeks. Both doses significantly reduced body weight, serum LDL, total cholesterol, triglycerides, insulin, and IL-1β levels. Conversely, HDL and adiponectin levels increased. Histopathological analysis showed improvements in liver and kidney tissues of treated rats. These findings suggest that our test compound could ameliorate obesity complications and serve as a potential therapeutic agent. Further pharmacological, toxicological, and clinical studies are needed to confirm its utility.

The triglyceride-glucose (TyG) index is a practical surrogate of insulin resistance, but evidence on its association with hyperuricemia (HUA) in young adults is limited. We examined the nonlinear association between TyG and HUA in a young Chinese population. This cross-sectional study included 6343 adults aged 18-45 years who underwent routine health examinations at the Chinese PLA General Hospital. Participants were categorized into TyG quartiles. Multivariable logistic regression with stepwise adjustment for demographic, body composition, and metabolic covariates was used to evaluate the association between TyG and prevalent HUA. Restricted cubic splines (RCSs) assessed potential nonlinearity, and stratified analyses were performed across subgroups. The mean age was 33.7±7.1 years, and 73.5% were male; the prevalence of HUA was 28.4%. The proportion of HUA increased across TyG quartiles from 14.0% in Q1 to 51.3% in Q4 (p < 0.001). In fully adjusted models, the highest TyG quartile was associated with higher odds of HUA compared with Q1 (adjusted odds ratio [OR] 2.26, 95% confidence interval [CI] 1.46-3.51). RCS analysis demonstrated a significant nonlinear relationship (p for nonlinearity < 0.001) with a change in the slope around TyG = 8.278. Below this threshold, the association was not significant (OR 0.629, 95% CI 0.24-1.652), whereas above it the odds increased sharply (OR 5.846, 95% CI 3.718-9.193). Findings were consistent in stratified analyses. Overall, TyG is independently and nonlinearly associated with HUA in young adults, supporting its potential utility for early risk identification.

Paediatric metabolic dysfunction-associated steatotic liver disease (MASLD) and steatohepatitis (MASH) display a distinct and severe histopathology. Maternal metabolic status may program offspring susceptibility to MASLD. This study investigated if maternal dyslipidaemia and low vitamin C (VitC) status influence offspring MASLD using a validated guinea pig model. Thirty female guinea pigs received a low-fat (LF) diet until pregnancy was confirmed, then remained on LF or switched to a high-fat (HF) diet with or without reduced VitC. Offspring were evaluated at birth and after 10 weeks on postweaning HF or LF diets. In dams, HF diet induced dyslipidaemia and elevated hepatic triglycerides and alanine aminotransferase (ALT) compared to LF dams, without causing obesity. Newborns exposed to maternal HF diet showed increased hepatic triglycerides, liver-to-body weight ratio and ALT. By 10 weeks, liver fibrosis and MASLD activity scores were higher in offspring maintained on a postnatal HF diet compared to LF. Notably, offspring viability was markedly reduced on maternal HF diet with low VitC. These findings demonstrate that even short exposure to maternal HF diet, independent of obesity, can adversely affect offspring MASLD risk and highlight the need for early prevention. Additionally, findings support the need to investigate interactions between maternal diet, VitC status and offspring survival.

Early identification of individuals at risk of type 2 diabetes is important in young and middle-aged adults. Although the homeostatic model assessment of insulin resistance (HOMA-IR) is widely used, its limited clinical practicality has increased interest in the triglyceride-glucose (TyG) index as a simpler surrogate marker of insulin resistance. However, the predictive values of longitudinal changes in these indices remain unclear. We analyzed data from 271,592 Korean adults aged 18-49 years who underwent at least two health screening examinations. Changes in the TyG index and HOMA-IR were categorized into sex-specific quintiles. Incident type 2 diabetes was defined as fasting glucose ≥ 126 mg/dL, HbA1c ≥ 6.5%, or initiation of antidiabetic medication. Hazard ratios were estimated using the Cox proportional hazard models. During the follow-up period, 3,841 men and 1,069 women developed type 2 diabetes. Greater increases in the TyG index were consistently associated with a higher risk of diabetes across quintiles in both sexes. The associations with HOMA-IR changes were more variable across analytical models, particularly in the lower quintiles. These findings suggest that monitoring changes in both indices may provide additional information for diabetes risk assessment, with the TyG index showing more consistent associations across models in our study. Further studies in diverse populations are needed to confirm these observations.