International Journal of Molecular Zoology 2024, Vol.14, No.4, 211-221 http://animalscipublisher.com/index.php/ijmz 217 The study of Ziqubu et al. (2023) illustrates the multifaceted effects of metformin on various tissues in the context of metabolic syndrome. Metformin acts primarily by activating AMPK, which helps reduce glucose production in the liver, enhances insulin sensitivity in skeletal muscles, and decreases fat accumulation in adipose tissue. Additionally, metformin improves cardiovascular health by lowering LDL levels and enhancing endothelial function. It also positively impacts the gut microbiota, leading to improved glucose utilization and reduced hyperglycemia and body weight. Overall, metformin addresses several key aspects of metabolic syndrome, making it a widely used therapeutic agent. 5.4 Case examples and clinical trials Several clinical trials have investigated the effects of various interventions on BAT activity and their potential therapeutic benefits. For instance, a systematic review of clinical trials testing the impact of agents such as β-agonists, capsinoids, and cold exposure on BAT activation revealed significant heterogeneity in the duration of interventions and metrics used to estimate thermogenesis and energy expenditure. Despite the observed activation of BAT, the studies did not consistently correlate with significant weight loss, highlighting the need for further research to determine the long-term efficacy and safety of these interventions. Another study demonstrated that BAT transplantation in mice improved glucose tolerance, increased insulin sensitivity, and reversed high-fat diet-induced insulin resistance, suggesting a potential role for BAT in regulating glucose homeostasis and insulin sensitivity (Stanford et al., 2013). These findings underscore the therapeutic potential of targeting BAT for treating metabolic diseases and warrant further investigation in larger, well-designed clinical trials. 6 Comparative Analysis: BAT in Different Mammals 6.1 Differences in BAT function across species Brown adipose tissue (BAT) plays a crucial role in thermogenesis and energy metabolism across various mammalian species. However, the function and efficiency of BAT can vary significantly. For instance, in neonatal mammals, BAT is essential for preventing hypothermia by activating biochemical and endocrine processes in response to cold stress. The presence and activation of BAT, as well as its location and thermogenic response, depend on both intrinsic and extrinsic factors unique to each species (Bienboire-Frosini et al., 2023). In small mammalian hibernators, BAT has evolved to have a high capacity for heat production, which is critical for rewarming from hypothermic torpor during hibernation (Ballinger and Andrews, 2018). In contrast, adult humans have been found to possess metabolically active BAT, which plays a role in energy expenditure and glucose homeostasis, although its prevalence and activity decrease with age and higher body mass index. 6.2 Evolutionary perspectives on BAT The evolutionary history of BAT and its thermogenic function is deeply rooted in the adaptation of mammals to diverse ecological niches. The presence of mitochondrial uncoupling protein 1 (UCP1) in BAT is a key evolutionary trait that enables adaptive thermoregulation through heat production. Studies on non-model organisms have broadened our understanding of BAT regulation and its physiological roles, highlighting the unique evolutionary adaptations of BAT in different species (Jastroch et al., 2018). For example, the ability of small mammalian hibernators to use BAT for rewarming from torpor is a specialized adaptation that has uncovered new molecular mechanisms and potential strategies for biomedical applications. The comparative biology of BAT across species provides insights into conserved and specialized functional changes, emphasizing the importance of considering species diversity, ecology, and evolution in BAT research. 6.3 Comparative case studies Several case studies illustrate the diverse roles and adaptations of BAT in different mammals. In neonatal mammals, BAT is vital for thermogenesis and preventing hypothermia, with its distribution, amount, and efficiency varying among species. In small mammalian hibernators, BAT's high thermogenic capacity is crucial for survival during hibernation, with recent research uncovering the molecular pathways involved in BAT regulation and function. In adult humans, the rediscovery of metabolically active BAT has led to a renewed interest in its potential therapeutic applications for obesity and metabolic disorders. Human BAT activity has been shown to correlate positively with energy expenditure during cold exposure and negatively with age and body
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