International Journal of Molecular Zoology 2024, Vol.14, No.4, 211-221 http://animalscipublisher.com/index.php/ijmz 216 (UCP1) (Wang et al., 2021). This thermogenic activity makes BAT an attractive target for combating obesity and related metabolic diseases. Studies have shown that individuals with higher BAT activity tend to have lower body mass index (BMI), improved insulin sensitivity, and better glucose metabolism (Singh et al., 2021). Conversely, reduced BAT activity is associated with obesity and metabolic complications such as insulin resistance and type 2 diabetes (T2D) (Maliszewska and Krętowski, 2021). Therefore, enhancing BAT activity could be a promising strategy for treating obesity and its associated disorders. 5.3 Therapeutic approaches targeting BAT in mammalian health Several therapeutic approaches have been explored to activate BAT and enhance its thermogenic capacity. Pharmacological agents such as β-agonists, capsinoids, thyroid hormone, sildenafil, and caffeine have been investigated for their potential to stimulate BAT activity and promote weight loss (Perez et al., 2022). Metformin, a widely used anti-diabetic drug, has also been shown to enhance BAT thermogenic activity by upregulating key thermogenic transcriptional factors and molecular markers involved in glucose metabolism and energy regulation (Figure 3) (Ziqubu et al., 2023). Additionally, cold exposure has been consistently demonstrated to activate BAT and induce thermogenesis, although its long-term feasibility as a therapy remains uncertain. Targeting AMP-activated protein kinase (AMPK) in BAT has emerged as another promising strategy, as it plays a significant role in regulating BAT's metabolic activity and non-shivering thermogenesis (Desjardins and Steinberg, 2018). These therapeutic approaches hold potential for improving metabolic health by increasing energy expenditure and reducing obesity-related complications. Figure 3 An overview of the most prominent mechanisms of action and impact of metformin on different metabolic diseases in conditions of metabolic syndrome (Adopted from Ziqubu et al., 2023) Image caption: AMPK: AMP-activated protein kinase, cAMP: cyclic adenosine monophosphate, FGF21: fibroblast growth factor 21, GLP-1R: glucagon-like peptide 1 receptor, LDL: low-density lipoprotein (Adopted from Ziqubu et al., 2023)
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