Brown adipose tissue
|This article is outdated. (January 2015)|
|Brown adipose tissue|
Brown adipose tissue in a woman shown in a PET/CT exam
|Latin||textus adiposus fuscus|
It is especially abundant in newborns and in hibernating mammals. Its primary function is to generate body heat in animals or newborns that do not shiver. In contrast to white adipocytes (fat cells), which contain a single lipid droplet, brown adipocytes contain numerous smaller droplets and a much higher number of (iron-containing) mitochondria, which make it brown. Brown fat also contains more capillaries than white fat, since it has a greater need for oxygen than most tissues.
Brown fat cells and muscle cells both seem to be derived from the same stem cells in the embryo. Both have the same marker on their surface (myogenic factor 5 (Myf5), which white fat cells do not have).
Brown fat cells and muscle cells both come from the middle embryo layer. The three layers of the embryo during the gastrulation stage are ectoderm, mesoderm, endoderm. Mesoderm is the source of myocytes (muscle cells), adipocytes, and chondrocytes (cartilage cells). Adipocytes give rise to white fat cells and brown fat cells.
Researchers found that both muscle and brown fat cells expressed the same muscle factor Myf5, whereas white fat cells did not. This suggested that muscle cells and brown fat cells were both derived from the same type of stem cell. Furthermore, muscle cells that were cultured with the transcription factor PRDM16 were converted into brown fat cells, and brown fat cells without PRDM16 were converted into muscle cells.
However, there may be two types of brown fat cells—with and without Myf5. The other type, without Myf5, may share the same origin as white fat cells. They both seem to be derived from pericytes, the cells which surround the blood vessels that run through white fat tissue.
The mitochondria in an eukaryotic cell utilize fuels to produce energy in the form of adenosine triphosphate (ATP). This process involves storing energy as a proton gradient, also known as the proton motive force (PMF), across the mitochondrial inner membrane. This energy is used to synthesize ATP when the protons flow across the membrane (down their concentration gradient) through the ATP synthase enzyme; this is known as chemiosmosis.
In endotherms, body heat is maintained by signaling the mitochondria to allow protons to run back along the gradient without producing ATP (proton leak). This can occur since an alternative return route for the protons exists through an uncoupling protein in the inner membrane. This protein, known as uncoupling protein 1 (thermogenin), facilitates the return of the protons after they have been actively pumped out of the mitochondria by the electron transport chain. This alternative route for protons uncouples oxidative phosphorylation and the energy in the PMF is instead released as heat.
To some degree, all cells of endotherms give off heat, especially when body temperature is below a regulatory threshold. However, brown adipose tissue is highly specialized for this non-shivering thermogenesis. First, each cell has a higher number of mitochondria compared to more typical cells. Second, these mitochondria have a higher-than-normal concentration of thermogenin in the inner membrane.
In neonates (newborn infants), brown fat makes up about 5% of the body mass and is located on the back, along the upper half of the spine and toward the shoulders. It is of great importance to avoid hypothermia, as lethal cold is a major death risk for premature neonates. Numerous factors make infants more susceptible to cold than adults:
- The higher ratio of body surface area (proportional to heat loss) to body volume (proportional to heat production and rate of cooling)
- The higher proportional surface area of the head
- The low amount of musculature and the inability or reluctance to shiver
- A lack of thermal insulation, e.g., subcutaneous fat and fine body hair (especially in prematurely born children)
- The inability to move away from cold areas, air currents or heat-draining materials
- The inability to use additional ways of keeping warm (e.g., drying their skin, putting on clothing, moving into warmer areas, or performing physical exercise)
- The nervous system is not fully developed and does not respond quickly and/or properly to cold (e.g., by contracting blood vessels in and just below the skin: vasoconstriction).
Heat production in brown fat provides an infant with an alternative means of heat regulation.
It was believed that after infants grow up, most of the mitochondria (which are responsible for the brown color) in brown adipose tissue disappear, and the tissue becomes similar in function and appearance to white fat. However, more recent research has shown that brown fat is related not to white fat, but to skeletal muscle.
Further, recent studies using Positron Emission Tomography scanning of adult humans have shown that it is still present in adults in the upper chest and neck (especially paravertebrally). The remaining deposits become more visible (increasing tracer uptake, that is, more metabolically active) with cold exposure, and less visible if an adrenergic beta blocker is given before the scan. The recent study could lead to a new method of weight loss, since brown fat takes calories from normal fat and burns it. Scientists were able to stimulate brown fat growth in mice, but human trials have not yet begun. However, recently published results from study of mouse models demonstrate that cold exposure promotes atherosclerotic plaque growth and instability from activation of brown fat. It should be noted that the article describes mice subjected to sustained low temperatures of 4°C for 8 weeks, which may cause a stress condition that shows rapid forced change rather than a safe acclimatisation that can be used to understand the growth of brown fat in adult humans during modest but comfortable reductions of ambient temperature by just 5 to 10 °C. Long term studies of adult humans are needed to establish a balance of benefit and risk, in combination with historical research of living conditions of recent human generations prior to the current increase of poor health related to excessive accumulation of white fat. Pharmacological approaches using β3-adrenoceptor agonists have been shown to enhance glucose metabolic activity of brown adipose tissue in rodents.
The interscapular brown adipose tissue is commonly and inappropriately referred to as the hibernating gland. Whilst believed by many to be a type of gland, it is actually a collection of adipose tissues lying between the scapulae of rodentine mammals. Composed of brown adipose tissue and divided into two lobes, it resembles a primitive gland, regulating the output of a variety of hormones. The function of the tissue appears to be involved in the storage of medium to small lipid chains for consumption during hibernation. The smaller lipid structure allowing for a more rapid path of energy production than glycolysis.
In studies where the interscapular brown adipose tissue of rats were lesioned, it was demonstrated that the rats had difficulty regulating their normal body-weight.
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- Histology image: 04901lob – Histology Learning System at Boston University – "Connective Tissue: multilocular (brown) adipocytes"