The global epidemic of obesity is tightly associated with numerous comorbidities, such as type II diabetes, cardiovascular diseases and the metabolic syndrome. Among the key features of obesity, some studies have suggested the abnormal expansion of adipose-tissue-induced local endogenous hypoxic, while other studies indicated endogenous hyperoxia as the opposite trend. Endogenous hypoxic aggravates dysfunction in adipose tissue and stimulates secretion of inflammatory molecules, which contribute to obesity. In contrast, hypoxic exposure combined with training effectively generate exogenous hypoxic to reduce body weight and downregulate metabolic risks. The (patho)physiological effects in adipose tissue are distinct from those of endogenous hypoxic. We critically assess the latest advances on the molecular mediators of endogenous hypoxic that regulate the dysfunction in adipose tissue. Subsequently we propose potential therapeutic targets in adipose tissues and the small molecules that may reverse the detrimental effect of local endogenous hypoxic. More importantly, we discuss alterations of metabolic pathways in adipose tissue and the metabolic benefits brought by hypoxic exercise. In terms of therapeutic intervention, numerous approaches have been developed to treat obesity, nevertheless durability and safety remain the major concern. Thus, a combination of the therapies that suppress endogenous hypoxic with exercise plans that augment exogenous hypoxic may accelerate the development of more effective and durable medications to treat obesity and comorbidities.

Objective: This systematic review and meta-analysis aimed to evaluate the effects of exercise interventions on cognitive function in diabetes. Methods: We conducted a comprehensive search of the Web of Science, PubMed, Scopus, EMBASE (Ovid), and SPORTDiscus databases from inception to December 2025 (registration number: CRD420251046731). The review included randomized controlled trials focusing on exercise interventions for diabetes and their impact on 4 cognitive domains: executive function, memory, attention, and global cognition. Subgroup and moderator analyses were performed based on exercise variables, including exercise type, session duration, total weekly exercise time, and intervention period. Study quality was assessed using the Cochrane Risk of Bias Tool 2 and the Physical Therapy Evidence Database scale (PEDro scale). Results: After screening 6230 records, 16 studies were included. Exercise interventions produced small-to-medium significant improvements in memory and global cognition in patients with diabetes, whereas the overall pooled effect on executive function was not statistically significant. Subgroup analyses suggested potential trends toward improvement in executive function for aerobic exercise (Hedge’s g = −0.30, p = 0.0039), single sessions ≥ 45 min (Hedge’s g = −0.40, p = 0.0463), and intervention periods ≥ 24 weeks (Hedge’s g = −0.27, p = 0.0383). For memory, aerobic (Hedge’s g = 0.27, p = 0.0131) or multicomponent exercise (Hedge’s g = 0.45, p = 0.0224) with single sessions ≤ 60 min (Hedge’s g = 0.28, p = 0.002), total weekly exercise time ≤ 120 min (Hedge’s g = 0.35, p = 0.0012), and interventions ≥ 12 weeks (Hedge’s g = 0.32, p = 0.0003) were significantly beneficial. Exercise also had a significant positive effect on global cognition (Hedge’s g = 0.49, p < 0.0001) without significant differences across exercise variables. In addition, exercise intervention showed a borderline, non-significant trend toward improved motor performance in patients with diabetes (Hedge’s g = 0.33, p = 0.0506). Conclusions: This comprehensive meta-analysis supports the beneficial effects of exercise on global cognition and memory in patients with diabetes. For memory enhancement, aerobic or multicomponent exercise protocols of ≥12 weeks, ≤120 min of total weekly exercise, and ≤60 min per session are more recommended. Although the overall pooled effect on executive function did not reach statistical significance, exploratory subgroup findings point toward potential domain-specific benefits under targeted exercise parameters (such as aerobic exercise of longer duration). These dose–response patterns should therefore be viewed as exploratory and hypothesis-generating, warranting confirmation in adequately powered, head-to-head trials before specific exercise prescriptions can be recommended.