adipose tissue, body fat, or simply fat is a loose connective tissue composed mostly of adipocytes. In addition to adipocytes, adipose tissue contains the stromal vascular fraction (SVF) of cells including preadipocytes, fibroblasts, vascular endothelial cells and a variety of immune cells such as adipose tissue macrophages. Adipose tissue is derived from preadipocytes. Its main role is to store energy in the form of lipids, although it also cushions and insulates the body. Far from being hormonally inert, adipose tissue has, in recent years, been recognized as a major endocrine organ, as it produces hormones such as leptin, estrogen, resistin, and cytokine (especially TNFα). The two types of adipose tissue are white adipose tissue (WAT), which stores energy, and brown adipose tissue (BAT), which generates body heat. The formation of adipose tissue appears to be controlled in part by the adipose gene. Adipose tissue – more specifically brown adipose tissue – was first identified by the Swiss naturalist Conrad Gessner in 1551.
In humans, adipose tissue is located: beneath the skin (subcutaneous fat), around internal organs (visceral fat), in bone marrow (yellow bone marrow), intermuscular (Muscular system) and in the breast (breast tissue). Adipose tissue is found in specific locations, which are referred to as adipose depots. Apart from adipocytes, which comprise the highest percentage of cells within adipose tissue, other cell types are present, collectively termed stromal vascular fraction (SVF) of cells. SVF includes preadipocytes, fibroblasts, adipose tissue macrophages, and endothelial cells.
Brown fat or brown adipose tissue (BAT) is a specialized form of adipose tissue important for adaptive thermogenesis in humans and other mammals. BAT can generate heat by "uncoupling" the respiratory chain of oxidative phosphorylation within mitochondria through tissue-specific expression of uncoupling protein 1 (UCP1). BAT is primarily located around the neck and large blood vessels of the thorax, where may effectively act in heat exchange. BAT is robustly activated upon cold exposure by the release of catecholamines from sympathetic nerves that results in UCP1 activation. BAT activation may also occur in response to overfeeding. UCP1 activity is stimulated by long chain fatty acids that are produced subsequent to β-adrenergic receptor activation. UCP1 is proposed to function as a fatty acid proton symporter, although the exact mechanism has yet to be elucidated. In contrast, UCP1 is inhibited by ATP, ADP, and GTP.
Browning of WAT
Browning of WAT, also referred to as "beiging", occurs when adipocytes within WAT depots develop features of BAT. Beige adipocytes take on a multilocular appearance (containing several lipid droplets) and increase expression of uncoupling protein 1 (UCP1).In doing so, these normally energy-storing adipocytes become energy-releasing adipocytes.
The calorie-burning capacity of brown and beige fat has been extensively studied as research efforts focus on therapies targeted to treat obesity and diabetes. The drug 2,4-dinitrophenol, which also acts as a chemical uncoupler similarly to UCP1, was used for weight loss in the 1930s. However, it was quickly discontinued when excessive dosing led to adverse side effects including hyperthermia and death.β3 agonists, like CL316,243, have also been developed and tested in humans. However, the use of such drugs has proven largely unsuccessful due to several challenges, including varying species receptor specificity and poor oral bioavailability.
Endocrinology and Metabolism: Open Access
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