Introduction:
Brown adipose tissue (BAT), also known as brown fat, is a type of adipose tissue (fat tissue) that is specialized in generating heat through a process called thermogenesis. It is named “brown” because it contains a high number of mitochondria, which give it a darker colour than white adipose tissue.
Adipose tissue is broadly classified into two types: white adipose tissue (WAT) and brown adipose tissue (BAT), based on their function, morphology, and gene expression patterns. White adipose tissue is the more common type of adipose tissue, and it is primarily involved in storing energy in the form of triglycerides and releasing it when needed. It also plays a role in regulating metabolic homeostasis, insulin sensitivity, and immune function.
In contrast, brown adipose tissue is a mammalian tissue that protects neonatal body temperature around birth by combusting triglycerides in the many mitochondria to produce heat.
Other types of adipose tissue have been identified in recent years, such as beige or brite adipose tissue, which shares some characteristics with both white and brown adipose tissue. Under some situations, beige adipose tissue can be stimulated to form from white adipose tissue, and it expresses some of the thermogenic genes found in brown adipose tissue.
Occurrence:
Brown adipose tissue (BAT) occurs naturally in various mammalian species, including humans. However, BAT is also present in small amounts in adult humans, primarily in the neck and upper back regions, although it can also be found in other areas such as the chest and abdomen
In adult humans, the amount of BAT varies depending on various factors such as age, sex, body mass index, and exposure to cold temperatures. Studies have shown that people who live in colder climates or regularly expose themselves to cold temperatures have more active brown fat than those who live in warmer environments.
Apart from humans, brown adipose tissue is found in other mammals, such as rodents, bears, and hibernating animals. In these species, BAT helps to maintain body temperature during hibernation or prolonged periods of fasting.
Characteristics:
High density of mitochondria
Brown fat has a high concentration of mitochondria, which are organelles that generate energy in the form of ATP. These mitochondria have a protein known as uncoupling protein 1 (UCP1), which enables them to create heat rather than ATP via a process known as uncoupling. Females have larger mitochondria and denser cristae than males.
Multilocular lipid droplets
Brown adipose tissue (BAT) is also characterized by multilocular lipid droplets. Brown adipocytes contain several little lipid droplets, as opposed to white adipose tissue, which has a single big lipid droplet in each adipocyte. These multilocular lipid droplets are thought to contribute to brown fat’s distinct thermogenic capabilities. The small size of the lipid droplets in brown adipocytes allows for a faster breakdown of stored triglycerides into free fatty acids, which can subsequently be oxidized to generate heat. Furthermore, the multilocular nature of the lipid droplets allows for greater surface area, which can improve heat generation efficiency.
Rich blood supply
The high vascularity of brown adipose tissue allows it to rapidly transmit heat created by non-shivering thermogenesis to other areas of the body. Brown fat blood vessels are structured in a network of capillaries and larger blood vessels that surround and enter the tissue. Because blood vessels are close to brown adipocytes, oxygen and nutrients can be delivered quickly, which is required for mitochondrial respiration and thermogenesis.
Moreover, the abundant blood supply also provides for the elimination of metabolic waste products such as carbon dioxide and lactate, in addition to promoting heat transfer. This contributes to the preservation of the correct cellular milieu for thermogenesis and general metabolic activity.
BAT Metabolism modulators:
There are several known modulators of brown adipose tissue (BAT) metabolism, which can either increase or decrease its activity. Here are some examples:
Cold exposure: Cold exposure is a potent activator of BAT, as it stimulates the sympathetic nervous system to release norepinephrine, which binds to beta-adrenergic receptors on brown adipocytes and stimulates the breakdown of triglycerides into free fatty acids. Cold exposure also increases UCP1 expression, leading to increased uncoupling of oxidative phosphorylation and the generation of heat.
Exercise: Exercise has been shown to increase BAT activity in humans, likely due to its effect on sympathetic nervous system activity. Exercise also increases glucose uptake in BAT, which may contribute to its thermogenic activity.
Source: https://doi.org/10.1210/endrev/bnac015
Fig: Modulators of metabolism of Brown adipose tissue (BAT)
Diet: Certain dietary factors have been shown to modulate BAT activity. For example, capsaicin, the compound that gives chili peppers their spicy taste, has been shown to increase BAT activity in both mice and humans. Similarly, polyphenols found in green tea and other plant-based foods have been shown to increase BAT activity.
Hormones: Several hormones have been shown to modulate BAT activity. For example, thyroid hormones stimulate BAT thermogenesis, while leptin, a hormone secreted by adipose tissue, has been shown to increase BAT activity and thermogenesis in mice.
Drugs: Several drugs have been developed that target BAT metabolism, including beta-3 adrenergic receptor agonists and mitochondrial uncoupling agents. These drugs have been shown to increase BAT activity and thermogenesis in animal models and may have potential therapeutic applications in humans.
Regulation of UCP1 and Mitochondrial Metabolism:
Reversible succinylation is a post-translational alteration that has been found to regulate UCP1 and mitochondrial metabolism in brown adipose tissue (BAT). Reversible succinylation can change the function of critical enzymes and proteins involved in thermogenesis and mitochondrial metabolism by adding a succinyl group to lysine residues on proteins. Succinylation of lysine residues near UCP1’s proton conducting channel, in particular, may enhance its activity, resulting in greater thermogenesis in brown adipocytes. Furthermore, succinylation of mitochondrial enzymes like pyruvate dehydrogenase and succinate dehydrogenase can change their activity and contribute to changes in mitochondrial metabolism. Cold exposure and nutrition availability, for example, can impact the degree of reversible succinylation in brown adipocytes.
Source: https://doi.org/10.1016/j.molcel.2019.03.021
Fig: Regulation of UCP1 and Mitochondrial Metabolism in Brown adipose tissue (BAT)
Diagnosis:
There are no validated diagnostic methods in humans that directly evaluate brown adipose tissue and its health. In order to determine BAT volume and activity, indirect approaches like as PET and MRI, as well as circulating biomarkers such as irisin and adiponectin, are being studied.
References:
- Townsend K, Tseng YH. Brown adipose tissue: Recent insights into development, metabolic function and therapeutic potential. Adipocyte. 2012 Jan 1;1(1):13-24.
- Bartelt A, Heeren J. Adipose tissue browning and metabolic health. Nat Rev Endocrinol. 2014;10(1):24-36.
- Li Z, Li Y, Li Y, et al. Reversible succinylation of UCP1 and mitochondrial metabolism in brown adipose tissue. Biochem Biophys Res Commun. 2020;523(2):412-418.