International Journal of Molecular Zoology 2024, Vol.14, No.4, 211-221 http://animalscipublisher.com/index.php/ijmz 214 activity, leading to decreased thermogenesis and increased lipid accumulation. The image highlights the role of specific obesity-associated factors that negatively impact BAT function. Modulating these factors through pharmacological interventions could potentially restore BAT activity, offering a therapeutic approach to managing obesity and related metabolic disorders. Figure 2 Obesity-associated metabolic differences in human individuals and the brown adipocyte model (Adopted from Takeda et al., 2023) Image caption: Obese human individuals exhibit the repression of BAT mass and activity and lower BAT uptake of blood glucose and free fatty acids compared with those in lean individuals. Mechanistically, the repression is caused by obesity-associated factors that positively and negatively modulate adipocyte browning, de novo brown adipogenesis, UCP1 expression and activity, and adrenergic responses. The amount of the negative factors, such as TGF-β, Noggin, Notch, TNFα, and selenoprotein P, increases under obese conditions, whereas the amount of the positive factors such as BMP4 and Il-27 decreases. The pharmacological modulation of the metabolic pathways involved in these obesity-associated factors may provide therapeutic intervention in the management of obesity and metabolic diseases through brown fats. During the culture of the chemical compound-induced brown/beige adipocytes (ciBAs), the increase in free fatty acids (FFAs) in the culture medium induces white adipocyte-like phenotypes of ciBAs in terms of UCP1 expression and lipid metabolism, which may reflect BAT under obese conditions. In contrast, the depletion of FFAs or prolonged treatment with either carnitine or capsaicin causes the browning process of ciBAs, which may reflect BAT under lean conditions (Adopted from Takeda et al., 2023) 3.3 Impact of BAT on glucose and lipid metabolism BAT significantly influences glucose and lipid metabolism. It has been shown to improve glucose homeostasis and insulin sensitivity. For example, BAT transplantation in mice led to increased insulin-stimulated glucose uptake in various tissues, including endogenous BAT, white adipose tissue (WAT), and heart muscle, but not skeletal muscle. This indicates that BAT plays a crucial role in regulating glucose metabolism. Furthermore, BAT activation has been linked to enhanced lipid metabolism. Studies have demonstrated that BAT activation increases whole-body lipolysis, triglyceride-free fatty acid (FFA) cycling, FFA oxidation, and adipose tissue insulin sensitivity (Chondronikola et al., 2016). The ability of BAT to utilize glucose and lipids for thermogenesis and its potential endocrine functions, such as the secretion of regulatory molecules like IL-6, further underscore its role in maintaining metabolic homeostasis and combating metabolic diseases (Villarroya et al., 2017; Carpentier et al., 2018). 4 Regulation of BAT Activity 4.1 Genetic and epigenetic regulation The regulation of brown adipose tissue (BAT) activity is significantly influenced by genetic and epigenetic factors. Genetic determinants play a crucial role in the distribution, amount, and efficiency of BAT, particularly in newborn mammals, where these factors are vital for thermoregulation and survival (Bienboire-Frosini et al., 2023).
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