International Journal of Molecular Zoology 2024, Vol.14, No.4, 211-221 http://animalscipublisher.com/index.php/ijmz 212 2 Overview of Brown Adipose Tissue (BAT) Brown adipose tissue (BAT) is a specialized form of fat tissue that plays a crucial role in thermogenesis and energy metabolism in mammals. Unlike white adipose tissue (WAT), which stores energy, BAT dissipates energy as heat, contributing to the maintenance of body temperature and overall energy homeostasis. 2.1 Structure and function of BAT BAT is characterized by its high density of mitochondria, which contain uncoupling protein 1 (UCP1). UCP1 is essential for the thermogenic function of BAT, as it uncouples oxidative phosphorylation from ATP production, allowing the energy to be released as heat instead (Sidossis and Kajimura, 2015). This process, known as non-shivering thermogenesis, is particularly important in newborns and hibernating animals, where it helps to prevent hypothermia (Tews and Wabitsch, 2021). Additionally, BAT can utilize various substrates, including lipids, glucose, and amino acids, to fuel its thermogenic activity, making it a dynamic and flexible tissue in terms of metabolic function (Wang et al., 2021). 2.2 Distribution of BAT in mammals The distribution of BAT varies among different species and life stages. In humans, BAT is predominantly found in infants, with significant depots located in the cervical-supraclavicular regions, around the spine, and near the kidneys (Lee et al., 2013). While the relative mass of BAT declines with age, recent studies have shown that metabolically active BAT persists in some adults, particularly in the cervical and supraclavicular regions (Yuko and Saito, 2021). The presence and activity of BAT in adults are influenced by factors such as cold exposure, which can induce the browning of white adipose tissue, leading to the formation of beige adipocytes that share functional similarities with classical brown adipocytes (Kajimura et al., 2015). 2.3 Molecular mechanisms of BAT activation The activation of BAT is primarily regulated by the sympathetic nervous system through the release of norepinephrine, which binds to adrenergic receptors on brown adipocytes, triggering a cascade of intracellular events that lead to the activation of UCP1 and subsequent heat production (Figure 1) (Bienboire-Frosini et al., 2023). Additionally, several neurotrophic factors, known as batokines, such as NGF, NRG4, and S100b, play a role in the remodeling and sympathetic innervation of BAT, enhancing its thermogenic capacity (Robertson et al., 2023). Moreover, BAT secretes various paracrine and endocrine factors that influence systemic metabolism, suggesting that BAT functions as a metabolic regulator beyond its thermogenic role (Schéele and Wolfrum, 2019). The study of Bienboire-Frosini et al. (2023) illustrates the complex biochemical process by which brown adipose tissue (BAT) in mammals produces heat, particularly in response to cold environments. It shows the role of the sympathetic nervous system in activating BAT through the release of norepinephrine (NE), which binds to β3-adrenergic receptors (β3-AR) on brown fat cells. This triggers a cascade of events involving cAMP, PKA, and various transcription factors that ultimately increase the expression of UCP1 in mitochondria. UCP1 plays a key role in the production of heat through the process of non-shivering thermogenesis, utilizing fatty acids as fuel. In summary, BAT is a critical tissue for thermogenesis and energy metabolism in mammals. Its structure, distribution, and activation mechanisms are finely tuned to meet the thermogenic demands of the organism, making it a potential target for therapeutic strategies aimed at combating obesity and metabolic disorders. 3 Role of BAT in energy metabolism 3.1 Thermogenesis and heat production Brown adipose tissue (BAT) is specialized in expending energy through non-shivering thermogenesis, a process that produces heat by uncoupling protein 1 (UCP1)-dependent and UCP1-independent mechanisms (Shinde et al., 2021). This thermogenic capability allows BAT to burn calories through uncoupled respiration, producing heat to maintain body temperature, a feature that makes BAT a unique "energy sink" in mammals (Wang et al., 2021). The activation of BAT, particularly through cold exposure, leads to increased utilization of circulating blood glucose and fatty acids, contributing to thermogenesis and energy expenditure. This process is crucial for maintaining
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