Brown adipose tissue

Brown adipose tissue

Brown adipose tissue in a woman shown in a PET/CT exam
Details
Identifiers
Latin textus adiposus fuscus
TH H2.00.04.0.0004
FMA 20118

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, or white fat) found in mammals.

Importantly, classification of brown fat in humans refers to at least two distinct cell populations with similar functions. The first shares a common embryological origin with muscle cells, found in larger "classic" deposits. The second develops from adrenergically induced adipocytes, found interspersed in white adipose tissue.[1]

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

Histology

Brown fat in humans in the scientific and popular literature refers to two cell populations defined by both anatomical location and cellular morphology. Both share presence of small lipid droplets and numerous iron-rich mitochondria, giving the brown appearance.

Development

Brown fat cells come from the middle embryo layer, mesoderm, also the source of myocytes (muscle cells), adipocytes, and chondrocytes (cartilage cells).

The classic population of brown fat cells and muscle cells both seem to be derived from the same population of stem cells in the mesoderm, paraxial mesoderm. Both have the intrinsic capacity to activate the myogenic factor 5 (Myf5) promoter, a trait only associated with myocytes and this population of brown fat. Progenitors of traditional white fat cells and adrenergically induced brown fat do not have the capacity to activate the Myf5 promoter. Both adipocytes and brown adipocyte may be derived from pericytes, the cells which surround the blood vessels that run through white fat tissue.[1][4] Notably, this is not the same as the presence of Myf5 protein, which is involved in the development of many tissues.

Additionally, 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.[1]

Function

The mitochondria in a 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.

Infants

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:

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

Adults

Micrograph of a hibernoma, a benign tumour thought to arise from brown fat (haematoxylin and eosin 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.[5][6][7]

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 have been able to stimulate brown fat growth in mice.[8][9][10][11] A study of APOE knock out mice showed cold exposure promotes atherosclerotic plaque growth and instability from activation of brown fat.[12] However it should be noted that the study mice were 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. Furthermore, other models of cardiovascular disease show dramatic benefits of cold exposure in both animal and human studies which demonstrate that brown fat activation reduces plasma triglyceride and cholesterol levels and attenuates diet-induced atherosclerosis development.[13]

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.[14][15][16]

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

Other animals

The interscapular brown adipose tissue is commonly and inappropriately referred to as the hibernating gland.[17] 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.[18] Composed of brown adipose tissue and divided into two lobes, it resembles a primitive gland, regulating the output of a variety of hormones.[19][20][21] 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.[21]

See also

References

  1. 1 2 3 4 Enerbäck S (2009). "The origins of brown adipose tissue". New England Journal of Medicine 360 (19): 2021–2023. doi:10.1056/NEJMcibr0809610. PMID 19420373.
  2. ↑ Gesta S, Tseng YH, Kahn CR (October 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.
  3. ↑ Cedikova, Miroslava; Kripnerová, Michaela; Dvorakova, Jana; Pitule, Pavel; Grundmanova, Martina; Babuska, Vaclav; Mullerova, Dana; Kuncova, Jitka (2016-03-17). "Mitochondria in White, Brown, and Beige Adipocytes". Stem Cells International 2016: 1–11. doi:10.1155/2016/6067349. PMC 4814709. PMID 27073398.
  4. ↑ Haldar, Malay; Karan, Goutam; Tvrdik, Petr; Capecchi, Mario R. (2008-03-11). "Two Cell Lineages, myf5 and myf5-Independent, Participate in Mouse Skeletal Myogenesis". Developmental Cell 14 (3): 437–445. doi:10.1016/j.devcel.2008.01.002. ISSN 1534-5807. PMC 2917991. PMID 18331721.
  5. ↑ Nedergaard J, Bengtsson T, Cannon B (August 2007). "Unexpected evidence for active brown adipose tissue in adult humans". American Journal of Physiology. Endocrinology and Metabolism 293 (2): E444–52. doi:10.1152/ajpendo.00691.2006. PMID 17473055.
  6. ↑ Francesco S. Celi (9 April 2009). "Brown adipose tissue—when it pays to be inefficient". New England Journal of Medicine 360 (15): 1553. doi:10.1056/NEJMe0900466. PMC 2753374. PMID 19357412.
  7. ↑ Kolata, Gina (8 April 2009). "Calorie-burning fat? Studies say you have it". The New York Times. p. A1.
  8. ↑ Shingo Kajimura (27 August 2009). "Initiation of myoblast/brown fat switch through a PRDM16-C/EBP-β transcriptional complex". Nature 460: 1154–1158. doi:10.1038/nature08262. PMC 2754867. PMID 19641492.
  9. ↑ Kajimura S, Seale P, Kubota K; Seale, Patrick; Kubota, Kazuishi; Lunsford, Elaine; Frangioni, John V.; Gygi, Steven P.; Spiegelman, Bruce M.; et al. (August 2009). "Initiation of myoblast/brown fat switch through a PRDM16-C/EBP-β transcriptional complex". Nature 460 (7259): 1154–8. doi:10.1038/nature08262. PMC 2754867. PMID 19641492.
  10. ↑ Scientists Create Energy-burning Brown Fat In Mice Science Daily, July 30, 2009
  11. ↑ "‘Good fat’ could help manage type 2 diabetes". monash.edu. Monash University. Retrieved 24 November 2014.
  12. ↑ Dong, Mei; Yang, Xiaoyan; Lim, Sharon; Cao, Ziquan; Honek, Jennifer; Lu, Huixia; Zhang, Cheng; et al. (2 July 2013). "Cold exposure promotes atherosclerotic plaque growth and instability via UCP1-dependent lipolysis" (Short article). Cell Metabolism 18: 118–129. doi:10.1016/j.cmet.2013.06.003.
  13. ↑ Hoeke G, Kooijman S, Boon MR, Rensen PC, Berbée JF (8 January 2016). "Role of Brown Fat in Lipoprotein Metabolism and Atherosclerosis.". Circ Res. PMID 26837747.
  14. ↑ Mirbolooki, M. R.; Constantinescu, C. C.; Pan, M. L.; Mukherjee, J (2011). "Quantitative assessment of brown adipose tissue metabolic activity and volume using 18F-FDG PET/CT and β3-adrenergic receptor activation". EJNMMI Research 1 (1): 30. doi:10.1186/2191-219X-1-30. PMC 3250993. PMID 22214183.
  15. ↑ Mirbolooki, M. R.; Schade, K. N.; Constantinescu, C. C.; Pan, M. L.; Mukherjee, J (2015). "Enhancement of (18) F-fluorodeoxyglucose metabolism in rat brain frontal cortex using a β3 adrenoceptor agonist". Synapse 69 (2): 96–8. doi:10.1002/syn.21789. PMC 4275345. PMID 25347981.
  16. ↑ Mirbolooki, M. R.; Upadhyay, S. K.; Constantinescu, C. C.; Pan, M. L.; Mukherjee, J (2014). "Adrenergic pathway activation enhances brown adipose tissue metabolism: A ¹⁸FFDG PET/CT study in mice". Nuclear Medicine and Biology 41 (1): 10–6. doi:10.1016/j.nucmedbio.2013.08.009. PMC 3840120. PMID 24090673.
  17. ↑ Elroy F. Sheldon (1924). "The so-called hibernating gland in mammals: A form of adipose tissue". The Anatomical Record 28 (5): 331–347. doi:10.1002/ar.1090280502.
  18. ↑ Laura Austgen (2002-08-08). "Brown adipose tissue". Retrieved 2009-02-04.
  19. ↑ Nnodim, J. O. and Lever, J. D. (1985-12-01). "The pre- and postnatal development and ageing of interscapular brown adipose tissue in the rat". Anatomy and Embryology 173 (2): 215–223. doi:10.1007/BF00316302. PMID 4083523.
  20. ↑ Wassermann, F. (1965). "5: Adipose Tissue". In Renold, A. E. & Cahill, G. F., Jr., eds. Handbook of Physiology. Washington: American Physiological Society. pp. 87–100.
  21. 1 2 E. Connolly, R. D. Morriseyt, J. A. Carnie (1982). "The effect of interscapular brown adipose tissue removal on body-weight and cold response in the mouse". The British Journal of Nutrition 47 (3): 653–658. doi:10.1079/BJN19820077. PMID 6282304.

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