Adipose tissue

Adipose tissue is one of the main types of connective tissue.

In histology, adipose tissue or body fat or just fat is loose connective tissue composed of adipocytes. It is technically composed of roughly only 80% fat; fat in its solitary state exists in the liver and muscles. Adipose tissue is derived from lipoblasts. Its main role is to store energy in the form of fat, although it also cushions and insulates the body. Obesity or being overweight in humans and most animals does not depend on body weight but on the amount of body fat—to be specific, adipose tissue. Two types of adipose tissue exist: white adipose tissue (WAT) and brown adipose tissue (BAT). Adipose tissue also serves as an important endocrine organ[1] by producing hormones such as leptin, resistin, and the cytokine TNFα. The formation of adipose tissue appears to be controlled by the adipose gene. Adipose tissue was first identified by the Swiss naturalist Conrad Gessner in 1551.[2]

Contents

Anatomical features

In humans, adipose tissue is located beneath the skin (subcutaneous fat), around internal organs (visceral fat), in bone marrow (yellow bone marrow) and in breast tissue. Adipose tissue is found in specific locations, which are referred to as 'adipose depots.' Adipose tissue contains several cell types, with the highest percentage of cells being adipocytes, which contain fat droplets. Other cell types include fibroblasts, macrophages, and endothelial cells. Adipose tissue contains many small blood vessels. In the integumentary system, which includes the skin, it accumulates in the deepest level, the subcutaneous layer, providing insulation from heat and cold. Around organs, it provides protective padding. However, its main function is to be a reserve of lipids, which can be burned to meet the energy needs of the body. Adipose depots in different parts of the body have different biochemical profiles.

Mice

In mice, there are eight major adipose depots, four of which are within the abdominal cavity: The paired gonadal depots are attached to the uterus and ovaries in females and the epididymis and testes in males; the paired retroperitoneal depots are found along the dorsal wall of the abdomen, surrounding the kidney, and, when massive, extend into the pelvis. The mesenteric depot forms a glue-like web that supports the intestines, and the omental depot, which originates near the stomach and spleen, and, when massive, extends into the ventral abdomen. Both the mesenteric and omental depots incorporate much lymphoid tissue as lymph nodes and milky spots, respectively. The two superficial depots are the paired inguinal depots, which are found anterior to the upper segment of the hind limbs (underneath the skin) and the subscapular depots, paired medial mixtures of brown adipose tissue adjacent to regions of white adipose tissue, which are found under the skin between the dorsal crests of the scapulae. The layer of brown adipose tissue in this depot is often covered by a “frosting” of white adipose tissue; sometimes these two types of fat (brown and white) are hard to distinguish. The inguinal depots enclose the inguinal group of lymph nodes. Minor depots include the pericardial, which surrounds the heart, and the paired popliteal depots, between the major muscles behind the knees, each containing one large lymph node[3]. Of all the depots in the mouse, the gonadal depots are the largest and the most easily dissected[4], comprising about 30% of dissectible fat[5].

Obesity

In a severely obese person, excess adipose tissue hanging downward from the abdomen is referred to as a panniculus (or pannus). A panniculus complicates surgery of the morbidly obese. The panniculus may remain as a literal "apron of skin" if a severely obese person quickly loses large amounts of fat (a common result of gastric bypass surgery). This condition cannot be effectively corrected through diet and exercise alone, as the panniculus consists of adipocytes and other supporting cell types shrunken to their minimum volume and diameter. Reconstructive surgery is one method of treatment.

Abdominal fat

Visceral fat or abdominal fat[6] also known as organ fat or intra-abdominal fat, is located inside the abdominal cavity, packed in between organs (stomach, liver, kidneys, etc). Visceral fat is different than subcutaneous fat underneath the skin, and intramuscular fat interspersed in skeletal muscles. Fat in the lower body, as in thighs and buttocks, is subcutaneous, whereas fat in the abdomen is mostly visceral.[7] Visceral fat is composed of several adipose depots including mesenteric, epididymal white adipose tissue (EWAT) and perirenal depots.

An excess of visceral fat is known as central obesity, or "belly fat", in which the abdomen protrudes excessively. There is a strong correlation between central obesity and cardiovascular disease.[8] Excess visceral fat is also linked to diabetes[9], insulin resistance[10] inflammatory diseases,[11] and other obesity-related diseases.[12]

Female sex hormone causes fat to be stored in the buttocks, thighs, and hips in women.[13][14] Men are more likely to have fat stored in the belly due to sex hormone differences. When women reach menopause and the estrogen produced by ovaries declines, fat migrates from their buttocks, hips and thighs to their waists;[15] later fat is stored in the belly.[16]

High intensity exercise effectively reduces total abdominal fat.[17][18] At least 10 METs x hours per week in aerobic exercise is required for visceral fat reduction.[19]

Subcutaneous fat

Most of the remaining non-visceral fat is found just below the skin in a region called the hypodermis.[20] This subcutaneous fat is not related to many of the classic obesity-related pathologies, such as heart disease, cancer, and stroke, and there is even some evidence that it might be protective.[21] The typically female (or gynecoid) pattern of body fat distribution around the hips, thighs, and buttocks, is subcutaneous fat, and therefore poses less of a health risk compared to visceral fat.[22]

Like all other fat organs, subcutaneous fat is an active part of the endocrine system, secreting the hormones leptin and resistin.[23]

Physiology

Free fatty acid is liberated from lipoproteins by lipoprotein lipase (LPL) and enters the adipocyte, where it is reassembled into triglycerides by esterifying it onto glycerol. Human fat tissue contains about 87% lipids.

In humans, lipolysis is controlled through the balanced control of lipolytic B-adrenergic receptors and a2A-adrenergic receptor-mediated antilipolysis.

Fat is not laid down when there is surplus calories available and stored passively until it is needed; rather it is constantly being stored in and released from the adipose tissue .

Storage in the adipose tissue is catalysed by insulin, the activity of which is stimulated by high blood sugar

Fat cells have an important physiological role in maintaining triglyceride and free fatty acid levels, as well as determining insulin resistance. Abdominal fat has a different metabolic profile—being more prone to induce insulin resistance. This explains to a large degree why central obesity is a marker of impaired glucose tolerance and is an independent risk factor for cardiovascular disease (even in the absence of diabetes mellitus and hypertension).[24] Studies of female monkeys at Wake Forest University (2009) discovered that individuals suffering from higher stress have higher levels of visceral fat in their bodies. This suggests a possible cause-and-effect link between the two, wherein stress promotes the accumulation of visceral fat, which in turn causes hormonal and metabolic changes that contribute to heart disease and other health problems.[25]

Recent advances in biotechnology have allowed for the harvesting of adult stem cells from adipose tissue, allowing stimulation of tissue regrowth using a patient's own cells. In addition, it was reported that adipose-derived stem cells from both human and animals can be efficiently reprogrammed into induced pluripotent stem cells without the need for feeder cells[26]. The use of a patient's own cells reduces the chance of tissue rejection and avoids the ethical issues associated with the use of human embryonic stem cells.

Adipose tissue is the greatest peripheral source of aromatase in both males and females contributing to the production of estradiol.

Adipose derived hormones include:

Adipose tissues also secrete a type of cytokines (cell-to-cell signalling proteins) called adipokines (adipocytokines) which play a role in obesity-associated complications.

Brown fat

A specialised form of adipose tissue in humans, most rodents and small mammals, and some hibernating animals, is brown fat or brown adipose tissue. It is located mainly around the neck and large blood vessels of the thorax. This specialised tissue can generate heat by "uncoupling" the respiratory chain of oxidative phosphorylation within mitochondria. The process of uncoupling means that, when protons transit down the electrochemical gradient across the inner mitochondrial membrane, the energy from this process is released as heat rather than being used to generate ATP. This thermogenic process may be vital in neonates exposed to the cold, who then require this thermogenesis to keep warm as they are unable to shiver, or take other actions to keep themselves warm.[27]

Attempts to simulate this process pharmacologically have so far been unsuccessful (even lethal[28][29]). Techniques to manipulate the differentiation of "brown fat" could become a mechanism for weight loss therapy in the future, encouraging the growth of tissue with this specialized metabolism without inducing it in other organs.

Until recently, it was thought that brown adipose tissue was primarily limited to infants in humans, but new evidence has now overturned that belief. Metabolically active tissue with temperature responses similar to brown adipose was first reported in the neck and trunk of some human adults in 2007[30], and the presence of brown adipose in human adults was later verified histologically in the same anatomical regions.[31][32][33]

Genetics

The "thrifty gene" hypothesis (also called the Famine Hypothesis) states that in some populations the body would be more efficient at retaining fat in times of plenty, thereby endowing greater resistance to starvation in times of food scarcity. This hypothesis has been discredited by physical anthropologists, physiologists, and the original proponent of the idea itself.[34]

In 1995 Jeffrey Friedman, in his residency at Rockefeller University, discovered the protein that the genetically obese mouse lacked -- leptin. [35] Leptin is produced in the white adipose tissue and signals to the hypothalamus. When leptin levels drop, the body interprets this as loss of energy, and hunger increases. Mice lacking this protein eat until they are four times the normal size of mice.

Leptin however, plays a different role in diet-induced obesity in rodents and humans. Because adipocytes produce leptin, leptin levels are elevated in the obese. However, hunger remains, and when leptin levels drop due to weight loss, hunger increases. The drop of leptin is better viewed as a starvation signal than the rise of leptin as a satiety signal.[36] However, elevated leptin in obesity is known as leptin resistance. The changes that occur in the hypothalamus to result in leptin resistance in obesity currently the focus of obesity research.[37]

Gene defects in the leptin gene (ob) are rare in human obesity.[38] As of July, 2010, only fourteen individuals from five families have been identified worldwide that carry a mutated ob gene (one of which was the first ever identified cause of genetic obesity in humans) - two families of Pakistani origin living in the UK, one family living in Turkey, one in Egypt, and one in Austria[39][40][41][42][43] - and two other families have been found that carry a mutated ob receptor.[44][45] Others have been identified as genetically partially deficient in leptin, and in these individuals, leptin levels on the low end of the normal range can predict obesity.[46]

Several mutations of genes involving the melanocortins (used in brain signaling associated with appetite) and their receptors have also been identified as causing obesity in a larger portion of the population than leptin mutations.[47]

In 2007, researchers isolated the adipose gene, which those researchers hypothesize serves to keep animals lean during times of plenty. In that study, increased adipose gene activity was associated with slimmer animals.[48] Although its discoverers dubbed this gene the adipose gene, it is not a gene responsible for creating adipose tissue.

Physical properties

Adipose tissue has a density of ~0.9 g/ml [49] [0.9 kg/l]. Thus, a person with much adipose tissue will float more easily than a person with a lot of muscular tissue, since muscular tissue has a density of 1.06 g/ml[49] [1.06 kg/l].

Cultural and social role

Subcutaneous adipose tissue on a male.

Excess adipose tissue on a human can lead to medical problems. For a discussion of the aesthetic and medical significance of body shape, see dieting and obesity.

Body fat meter

A body fat meter is a widely available tool used to measure the percentage of fat in the human body. Different meters use various methods to determine the body fat to weight ratio. They tend to under-read body fat percentage.[50]

In contrast with clinical tools, one relatively inexpensive type of body fat meter uses the principle of bioelectrical impedance analysis (BIA) to determine an individual's body fat percentage. To achieve this, the meter passes a small, harmless, electric current through the body and measures the resistance, then uses information on the person's weight, height, age, and sex, to calculate an approximate value for the person's body fat percentage. The calculation measures the total volume of water in the body (lean tissue and muscle contain a higher percentage of water than fat), and estimates the percentage of fat based on this information. The result can fluctuate several percent depending on what one has eaten and how much water one has consumed prior to the analysis.

Additional images

Diagrammatic sectional view of the skin (magnified).

Yellow adipose tissue in paraffin section

Electronic instrument of body fat meter

See also

References

  1. ↑ Kershaw EE, Flier JS (2004). "Adipose tissue as an endocrine organ". J. Clin. Endocrinol. Metab. 89 (6): 2548–56. doi:10.1210/jc.2004-0395. PMID 15181022. 
  2. ↑ Cannon B, Nedergaard J. (2008). Developmental biology: Neither fat nor flesh. Nature. Aug 21;454(7207):947-8. PubMed
  3. ↑ Pond, Caroline M. (1998). The Fats of Life. Cambridge University Press. ISBN 0521635772. 
  4. ↑ Cinti, S (July 2005). "The adipose organ". Prostaglandins, leukotrienes, and essential fatty acids (Elsevier Science) 73 (0952-3278): 9–15. doi:10.1016/j.plefa.2005.04.010. PMID 15936182. 
  5. ↑ Bachmanov, Alexander; D. R. Reed, M. G. Tordoff, R. A. Price (March 2001). "Nutrient preference and diet-induced adiposity in C57BL/6ByJ and 129P3/J mice". Physiology & Behavior 72 (0031-9384): 603–613. doi:10.1016/S0031-9384(01)00412-7. PMID 11282146. 
  6. ↑ Fat on the Inside: Looking Thin is Not Enough, By Fiona Haynes, About.com
  7. ↑ Abdominal fat and what to do about it, President & Fellows of Harvard College
  8. ↑ Yusuf S, Hawken S, Ounpuu S, Dans T, Avezum A, Lanas F, McQueen M, Budaj A, Pais P, Varigos J, Lisheng L, INTERHEART Study Investigators. (2004). "Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study.". Lancet 364 (9438): 937–52. doi:10.1016/S0140-6736(04)17018-9. PMID 15364185. 
  9. ↑ C.T. Montague and S. O'Rahilly, "The perils of portliness: causes and consequences of visceral adiposity", Diabetes vol 49, pages 883-888 (2000)
  10. ↑ P.A. Kern, Ranganathan, et al, "Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance", Am J Physiol Endocrinol Metab vol 280 pages E745-E751 (2001),
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  12. ↑ A.H. Mokdad, E.S. Ford, et al, "Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001", JAMA vol 289 pages 76-79 (2003)
  13. ↑ Estrogen causes fat to be stored around the pelvic region, hips, butt and thighs (pelvic region) [1]
  14. ↑ Waistline Worries: Turning Apples Back Into Pears
  15. ↑ Researchers think that the lack of estrogen at menopause play a role in driving our fat northward [2]
  16. ↑ Abdominal fat and what to do about it
  17. ↑ PMID 18845966 (PubMed)
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  18. ↑ PMID 19196080 (PubMed)
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  19. ↑ PMID 17637702 (PubMed)
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  20. ↑ E Marieb and K Hoehn. Anatomy and Physiology, 3rd Edition. Benjamin Cummings 2008. ISBN 0-8053-0094-5
  21. ↑ Porter SA, Massaro JM, Hoffmann U, Vasan RS, O'Donnel CJ, Fox CS. Abdominal subcutaneous adipose tissue: a protective fat depot? Diabetes Care. 2009 Jun;32(6):1068-75. Epub 2009 Feb 24
  22. ↑ Mayo Clinic staff. Belly fat in women: How to keep it off. MayoClinic.com. URL http://www.mayoclinic.com/health/belly-fat/WO00128/METHOD=print. Access date July 2, 2010
  23. ↑ E Marieb and K Hoehn. Anatomy and Physiology, 3rd Edition. Benjamin Cummings 2008. ISBN 0-8053-0094-5
  24. ↑ Dhaliwal SS, Welborn TA. (May 2009) "Central obesity and multivariable cardiovascular risk as assessed by the Framingham prediction scores" Am J Cardiol. (American Journal of Cardiology) 103(10): pp. 1403-1407
  25. ↑ Alice Park (2009-08-08). "Fat-Bellied Monkeys Suggest Why Stress Sucks". Time. http://www.time.com/time/health/article/0,8599,1915237,00.html. Retrieved 2009-08-08. 
  26. ↑ Sugii et. al. (2010). Human and mouse adipose-derived cells support feeder-independent induction of pluripotent stem cells. Proc Natl Acad Sci USA. 107:3558-63. PubMed
  27. ↑ Himms-Hagen, J. (August 1990) "Brown adipose tissue thermogenesis: interdisciplinary studies" The FASEB Journal (Federation of American Societies for Experimental Biology) 4(11): pp. 2890-2898
  28. ↑ McFee RB, Caraccio TR, McGuigan MA, Reynolds SA, Bellanger P (2004). "Dying to be thin: a dinitrophenol related fatality". Veterinary and human toxicology 46 (5): 251–4. PMID 15487646. 
  29. ↑ Miranda EJ, McIntyre IM, Parker DR, Gary RD, Logan BK (2006). "Two deaths attributed to the use of 2,4-dinitrophenol". Journal of analytical toxicology 30 (3): 219–22. PMID 16803658. 
  30. ↑ Nedergaard J, Bengtsson T, Cannon B. (2007). Unexpected evidence for active brown adipose tissue in adult humans. Am J Physiol Endocrinol Metab. 293:E444-52. PubMed
  31. ↑ Virtanen KA, Lidell ME, Orava J, Heglind M, Westergren R, Niemi T, Taittonen M, Laine J, Savisto NJ, Enerback S, Nuutila P. Functional brown adipose tissue in healthy adults. N Engl J Med 2009;360:1518–1525
  32. ↑ van Marken Lichtenbelt WD, Vanhommerig JW, Smulders NM, Drossaerts JM, Kemerink GJ, Bouvy ND, Schrauwen P, Teule GJ. Cold-activated brown adipose tissue in healthy men. N Engl J Med 2009;360:1500–1508
  33. ↑ Cypess AM, Lehman S, Williams G, Tal I, Rodman D, Goldfine AB, Kuo FC, Palmer EL, Tseng YH, Doria A, Kolodny GM, Kahn CR. Identification and importance of brown adipose tissue in adult humans. N Engl J Med 2009;360:1509–1517
  34. ↑ Speakerman, John R. "Genetics of Obesity: Five Fundamental Problems with the Famine Hypothesis." Adipose Tissue and Adipokines in Health and Disease. 2007
  35. ↑ Pelleymounter MA, Cullen MJ, Baker MB, Hecht R, Winters D, Boone T, Collins F. Effects of the obese gene product on body weight regulation in ob/ob mice. Science. 1995 Jul 28;269(5223):540-3.
  36. ↑ Smith and Ravussin. "Role of the Adipocyte in Metabolism and Endocrine Function." Endocrinology. 2006.
  37. ↑ Morris DL, Rui L. Recent advances in understanding leptin signaling and leptin resistance. Am J Physiol Endocrinol Metab. 2009 Dec;297(6):E1247-59. Epub 2009 Sep 1
  38. ↑ Obes Res. 1997 Jan;5(1):30-5.
  39. ↑ Montague CT, Farooqi IS, Whitehead JP, Soos MA, Rau H, Wareham NJ, Sewter CP, Digby JE, Mohammed SN, Hurst JA, Cheetham CH, Earley AR, Barnett AH, Prins JB, O'Rahilly S. Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature. 1997 Jun 26;387(6636):903-8.
  40. ↑ Strobel A, Issad T, Camoin L, Ozata M, Strosberg AD. A leptin missense mutation associated with hypogonadism and morbid obesity. Nat Genet. 1998 Mar;18(3):213-5.
  41. ↑ Gibson WT, Farooqi IS, Moreau M, DePaoli AM, Lawrence E, O'Rahilly S, Trussell RA. Congenital leptin deficiency due to homozygosity for the Delta133G mutation: report of another case and evaluation of response to four years of leptin therapy. J Clin Endocrinol Metab. 2004 Oct;89(10):4821-6.
  42. ↑ Mazen I, El-Gammal M, Abdel-Hamid M, Amr K. A novel homozygous missense mutation of the leptin gene (N103K) in an obese Egyptian patient. Mol Genet Metab. 2009 Aug;97(4):305-8. Epub 2009 Apr 9.
  43. ↑ Fischer-Posovszky P, von Schnurbein J, Moepps B, Lahr G, Strauss G, Barth TF, Kassubek J, Mühleder H, Möller P, Debatin KM, Gierschik P, Wabitsch M. A new missense mutation in the leptin gene causes mild obesity and hypogonadism without affecting T cell responsiveness. J Clin Endocrinol Metab. 2010 Jun;95(6):2836-40. Epub 2010 Apr 9.
  44. ↑ Clément K, Vaisse C, Lahlou N, Cabrol S, Pelloux V, Cassuto D, Gourmelen M, Dina C, Chambaz J, Lacorte JM, Basdevant A, Bougnères P, Lebouc Y, Froguel P, Guy-Grand B. A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature. 1998 Mar 26;392(6674):398-401.
  45. ↑ Pankov YA. Adipose tissue as an endocrine organ regulating growth, puberty, and other physiological functions. Biochemistry (Mosc). 1999 Jun;64(6):601-9.
  46. ↑ Farooqi IS, Keogh JM, Kamath S, Jones S, Gibson WT, Trussell R, Jebb SA, Lip GY, O'Rahilly S. Partial leptin deficiency and human adiposity. Nature. 2001 Nov 1;414(6859):34-5.
  47. ↑ Farooqi IS, O'Rahilly S. Mutations in ligands and receptors of the leptin-melanocortin pathway that lead to obesity. Nat Clin Pract Endocrinol Metab. 2008 Oct;4(10):569-77. Epub 2008 Sep 9.
  48. ↑ Suh, Jae Myoung et al. (September 2007) "Adipose Is a Conserved Dosage-Sensitive Antiobesity Gene" Cell Metabolism 6(3): pp. 195-207 PubMed
  49. ↑ 49.0 49.1 Google Answers: Muscle Density vs. Fat Density
  50. ↑ "Body fat scales review and compare". 10 January 2010. http://www.choice.com.au/Reviews-and-Tests/Food-and-Health/Diet-and-exercise/Weight-loss/Body-fat-scales-review-and-compare.aspx. Retrieved 11 January 2010. 

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Histology: connective tissue
Classification
Proper/
Fibrous
Loose

Areolar · Reticular

non-fibrous: Adipose (Brown, White)
Dense
Dense irregular connective tissue (Submucosa, Dermis) · Dense regular connective tissue (Ligament, Tendon, Aponeurosis)
Mucous · Mesenchymal
Composition
Extracellular
matrix
(noncellular)
Ground substance
Tissue fluid

Reticular fibers: Collagen

Elastic fibers: Fibrillin (FBN1, FBN2, FBN3)
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Mast cell · Macrophage
see also soft tissue

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