Pancreatic β cell failure is a hallmark of diabetes. However, the causes of β cell failure remain incomplete. Here, we report the identification of tetranectin (TN), an adipose tissue–enriched secretory molecule, as a negative regulator of insulin secretion in β cells in diabetes. TN expression is stimulated by high glucose in adipocytes via the p38 MAPK/TXNIP/thioredoxin/OCT4 signaling pathway, and elevated serum TN levels are associated with diabetes. TN treatment greatly exacerbates hyperglycemia in mice and suppresses glucose-stimulated insulin secretion in islets. Conversely, knockout of TN or neutralization of TN function notably improves insulin secretion and glucose tolerance in high-fat diet–fed mice. Mechanistically, TN binds with high selectivity to β cells and inhibits insulin secretion by blocking L-type Ca ²⁺ channels. Our study uncovers an adipocyte–β cell cross-talk that contributes to β cell dysfunction in diabetes and suggests that neutralization of TN levels may provide a new treatment strategy for type 2 diabetes.

Background: The ketogenic diet (KD) has gained popularity as an efficient approach to weight loss and body fat loss. Concerns about reducing muscle mass and performance have been rising during weight loss, as muscle mass and functionality are crucial for health. However, the effects of the KD on muscles not only for athletes or trainers but also for adults with less physical exercise are still controversial. Methods: We conducted a thorough search of databases including Embase, PubMed, Cochrane Library, and Web of Science up to July 19, 2025. Three aspects of muscle assessment were conducted, including muscle mass, power and strength, aerobic metabolic capacity, and endurance. We included randomized and non-randomized controlled studies that compared the KD with other dietary interventions. Studies without control groups were excluded. A random-effects model would be utilized when significant differences in populations and interventions across studies were of concern. The GRADE system was employed to assess evidence quality, while evidence reliability was gauged via sensitivity analysis. Results: A total of 33 studies were analyzed, revealing no significant differences between the KD and other diets in muscle mass (WMD: 0.06, 95%CI: -1.97 to 2.09, p = 0.95), muscle power (countermovement jump: SMD: -0.06, 95%CI: -0.49 to 0.38, p = 0.80) and strength (squat: SMD: -0.19, 95%CI: -0.53 to 0.15, p = 0.27; bench press: SMD: -0.15, 95%CI: -0.49 to 0.18, p = 0.37). However, a significant decrease in fat-free mass (WMD: -0.48, 95%CI: -0.73 to -0.23, p < 0.001) and fat mass (WMD: -1.31, 95%CI: -2.06 to -0.57, p < 0.001) was observed in the KD group compared with the control group. The KD also improved fat oxidation (WMD: 0.13, 95%CI: 0.08 to 0.17, p < 0.001) and reduced respiratory exchange ratio (WMD: -0.07, 95%CI: -0.11 to -0.03, p < 0.001) during an exercise test. The VO_2max and VO_2max relative to body weight, treadmill time to exhaustion, and rating of perceived exertion were not significantly affected by KD. Conclusions: Among adult populations, KD can increase fat oxidation to modify muscle metabolism, while no significant reduction in muscle mass or strength was observed. Additional well-designed randomized controlled trials are warranted to definitively determine the effects of ketogenic diets on muscle parameters.

BACKGROUND The global rise in overweight and obesity has reached alarming levels, substantially increasing the risk of metabolic disorders such as dyslipidemia. We outlined the evolving trends in baseline blood lipid levels among patients experiencing overweight or obesity, as observed in placebo-controlled randomized trials, to address the unmet clinical requirements. AIM To assess long-term trends in lipid profiles in overweight or obese populations and their association with clinical and treatment factors. METHODS EMBASE, PubMed, Cochrane Library, and Web of Science databases were searched up to October 9, 2024. Randomized placebo-controlled trials of participants with overweight or obesity, with reports of baseline lipid levels, were included. The main outcome was a correlation between pooled baseline levels of triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) with study year. Subgroup analysis was conducted based on characteristics of the populations and intervention types. RESULTS A comprehensive meta-analysis encompassing 866 studies across nearly 60 countries and regions worldwide, involving 3300 participants, revealed significant temporal trends in baseline lipid profiles. The analysis revealed a significant decline in TG (Rs = -0.704, P < 0.001, I 2 = 98.6%), TC (Rs = -0.884, P < 0.001, I 2 = 99.6%), and LDL-C (Rs = -0.808, P < 0.001, I 2 = 96.8%) levels. In contrast, HDL-C (Rs = 0.336, P = 0.041, I 2 = 99.2%) levels exhibited a progressive increase over the study period. Subgroup analyses revealed that sex, body mass index, blood pressure, diabetes status, and type of intervention influenced the observed trends, especially with patients receiving pharmacological therapies demonstrating more pronounced improvements (TG: Rs = -0.449, P adj = 0.011; I 2 = 98.9%; TC: Rs = -0.650, P adj = 0.001; I 2 = 99.4%; HDL-C: Rs = 0.650, P adj = 0.002; I 2 = 98.6%; LDL-C: Rs = -0.417, P adj = 0.031; I ² = 98.0%). CONCLUSION Despite rising obesity rates, lipid control has improved over three decades among individuals with overweight or obesity, reflecting the positive impact of public health efforts and effective dyslipidemia treatment strategies.