The receptor known as peroxisome proliferator‐activated receptor gamma (PPAR γ ) is crucial for effective wound healing, and recent progress has given a deeper understanding of its complex functions. As a biological switch, PPAR γ regulates the immune response by shifting macrophages from promoting inflammation to supporting tissue regeneration, while suppressing pro‐inflammatory signals to create an ideal healing environment. At the cellular level, PPAR γ enhances the migration of keratinocytes and promotes re‐epithelialization, thereby accelerating the wound closure process. It also promotes the differentiation of preadipocytes and the formation of new blood vessels, making a significant contribution to tissue regeneration. At the molecular level, PPAR γ plays a dual role in guiding epithelial–mesenchymal transformation to aid healing while preventing excessive scarring. It improves mitochondrial efficiency to provide the energy needed for tissue repair. Despite these promising mechanisms, the clinical use of current PPAR γ agonists faces hurdles due to side effects and regulatory hurdles. Moving forward, research should aim to develop targeted delivery methods, tailor therapies to individual needs, and investigate how PPAR γ interacts synergistically with other signaling pathways, all of which are essential steps toward translating these findings into clinical practice.
Obesity is driven by chronic energy imbalance and is associated with multiple metabolic diseases. As adipocyte thermogenesis contributes to energy expenditure, it is being actively investigated as a possible target for obesity treatment. This review summarizes recent progress in the molecular regulation of adipocyte thermogenesis, focusing mainly on preclinical mechanistic evidence from cellular and animal studies, while discussing clinical and human data only where available. We review emerging regulators within the cAMP pathway, the PRDM16-PPARγ axis, and mitochondrial quality control and metabolism, together with other pathways that modulate brown and beige adipocyte function. We also discuss their metabolic effects in experimental obesity settings. Nevertheless, the therapeutic relevance of these findings remains uncertain because much of the evidence is still preclinical, and because translation is complicated by species differences, adipose depot heterogeneity, and the limited number of validated human studies. This review therefore offers an updated synthesis of recent mechanistic advances while emphasizing the key challenges that must be addressed before these insights can be reliably translated into obesity therapies.
Objective:We are aimed at investigating the relationships among muscle mass, physical activity, and calcaneal bone mineral density (BMD) in female university students, and exploring the mediating role of muscle mass in the association between physical activity and calcaneal BMD. Methods:Using stratified cluster sampling, 593 female university students aged 19-25 of different grades were selected. Anthropocentric characteristics, body composition, and calcaneal BMD were measured. Statistical methods including multiple linear/binary logistic regression models, mediation analyses, sensitivity analyses, and subgroup analysis were performed. Results:The normal and abnormal BMD groups significantly varied in both total skeletal muscle mass (TSM) and total skeletal muscle mass index (TSMI) (t[TSM] = 3.216, t[TSMI] = 3.304, p < 0.01), and also diverse in physical activity (p < 0.05). The increment in muscle mass might be related to an increase in BMD (β[TSM] = 0.089, β[TSMI] = 0.265, p < 0.01) and a decrease in the probability of abnormal BMD (β[TSM] = -0.193, β[TSMI] = -0.682, p < 0.01). The effect of physical activity on calcaneal BMD is significant (β = -0.109, p < 0.05). Muscle mass plays a mediating role in the relationship between physical activity and calcaneal BMD, and the subgroup mediation sensitivity analyses indicated that the mediation effect only in the overweight group had significant mediation effects and relatively high robustness (Rho = -0.2, R2_MR2_Y = 0.04). Conclusion:Muscle mass and physical activity both present a significant positive correlation with calcaneal BMD in female university students, and high activity level is a protective factor for abnormal BMD. Muscle mass performs a mediating role in the relationship of physical activity and calcaneal BMD in female university students of the overweight group.
Diabetic corneal neuropathy (DCN) is a clinically important yet frequently overlooked complication of diabetes mellitus, characterized by progressive corneal nerve loss, impaired epithelial wound healing, and ocular surface instability. Its pathogenesis is multifactorial, driven by chronic hyperglycemia, dyslipidemia, advanced glycation end-products (AGEs), mitochondrial dysfunction, oxidative stress, and persistent low-grade inflammation. These processes synergistically disrupt neurotrophic signaling and promote axonal degeneration. Current therapies—including lubricants, autologous serum eye drops, and topical nerve growth factor—provide symptomatic relief and can promote corneal nerve regeneration. However, their effects are often variable, incomplete, or transient, and they do not fully address the underlying metabolic, inflammatory, and mitochondrial drivers of DCN, underscoring the unmet need for disease-modifying treatments. Peroxisome proliferator-activated receptors (PPARs) have recently emerged as compelling therapeutic targets. These nuclear transcription factors regulate key metabolic and inflammatory pathways, including lipid homeostasis, mitochondrial function, and oxidative stress. Among them, PPARα appears particularly relevant for corneal integrity. PPARα-deficient mice exhibit mitochondrial dysregulation, delayed epithelial repair, abnormal angiogenesis, and significant corneal nerve loss. Conversely, pharmacological activation with fenofibrate or selective PPAR modulators restores mitochondrial integrity, enhances neurotrophin expression, and promotes functional axon regeneration. Human studies corroborate these findings; systemic fenofibrate increases corneal nerve fiber density and improves tear proteomic signatures in patients with Type 2 diabetes, while topical formulations may provide faster and more pronounced neurotrophic effects. Collectively, current evidence positions PPARs—particularly PPARα—as promising next-generation therapeutic targets for reprogramming corneal neurodegeneration. Future progress will require innovative ocular delivery systems, biomarker-guided patient stratification, and rigorously designed clinical trials to fully realize the translational potential of PPAR modulation in DCN.
