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Brown adipose tissue

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Brown adipose tissue
Brown adipose tissue in a woman shown in a PET/CT exam
Details
Identifiers
Latintextus adiposus fuscus
MeSHD002001
THH2.00.03.4.00004
FMA20118
Anatomical terminology

Brown adipose tissue (BAT) or brown fat is one of two types of fat or adipose tissue (the other being white adipose tissue) found in mammals.

It is especially abundant in newborns and in hibernating mammals.[1] 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.[2] Brown fat also contains more capillaries than white fat, since it has a greater need for oxygen than most tissues.

Biochemistry

The mitochondria in a eukaryotic cell utilize fuels to produce energy (in the form of 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 synthesise ATP when the protons flow across the membrane (down their concentration gradient) through the ATP synthase enzyme; this is known as chemiosmosis.

In warm-blooded animals, body heat is maintained by signaling the mitochondria to allow protons to run back along the gradient without producing ATP.[citation needed] 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.

Function in infants

In neonates (newborn infants), brown fat, which then 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, is of great importance to avoid lethal cold (hypothermia is a major death risk for premature neonates). Numerous factors make infants more susceptible to cold than adults:

  • The higher ratio of body surface (proportional to heat loss) to body volume (proportional to heat production)
  • 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). (Note that contracting these blood vessels has disadvantages, such as reducing immunity in the skin which could allow a skin or internal infection to develop, and perhaps reducing the rate at which the skin can heal.)

Heat production in brown fat provides a baby with an alternative means of heat regulation.

Presence in adults

Micrograph of a hibernoma, a benign tumour thought to arise from brown fat. H&E stain.

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.[3][4][5]

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. 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.[6][7]

In rare cases, brown fat continues to grow, rather than involuting; this leads to a tumour known as a hibernoma.

Embryology

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 (Myf5, myogenic factor), which white fat cells do not have.[2]

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 fat cells were both derived from the same 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.[2]

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.[2]

See also

References

  1. ^ Gesta S, Tseng YH, Kahn CR (2007). "Developmental origin of fat: tracking obesity to its source". Cell. 131 (2): 242–56. doi:10.1016/j.cell.2007.10.004. PMID 17956727. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  2. ^ a b c d Enerbäck S (2009). "The origins of brown adipose tissue". N Engl J Med. 360 (19): 2021–2023. doi:10.1056/NEJMcibr0809610. PMID 19420373.
  3. ^ Nedergaard J, Bengtsson T, Cannon B (2007). "Unexpected evidence for active brown adipose tissue in adult humans". Am. J. Physiol. Endocrinol. Metab. 293 (2): E444–52. doi:10.1152/ajpendo.00691.2006. PMID 17473055. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  4. ^ Brown adipose tissue -- when it pays to be inefficient, Francesco S. Celi, N Engl J Med, 360:1553, Apr. 9, 2009
  5. ^ Kolata, Gina (8 April 2009). "Calorie-Burning Fat? Studies Say You Have It". The New York Times. p. A1.
  6. ^ Shingo Kajimura; et al. (27 August 2009). "Initiation of myoblast/brown fat switch through a PRDM16-C/EBP-β transcriptional complex" (Advance Online Edition). Nature. 460 (7259): 1154–1158. doi:10.1038/nature08262. PMC 2754867. PMID 19641492. {{cite journal}}: More than one of |magazine= and |journal= specified (help); Unknown parameter |author-separator= ignored (help)
  7. ^ Scientists Create Energy-burning Brown Fat In Mice Science Daily, July 30, 2009
  • Histology image: 04901lob – Histology Learning System at Boston University - "Connective Tissue: multilocular (brown) adipocytes"