Editing Adipocyte

{{Short description|Cells that primarily compose adipose tissue, specialized in storing energy as fat}}
{{Infobox cell
| Name        = Adipocyte
| Latin       = adipocytus
| Image       = Blausen 0012 AdiposeTissue.png
| Caption     = Illustration depicting white fat cells.
| Image2      = Adipocyte types.jpg
| Caption2    = Morphology of three different classes of adipocytes
| Precursor   =
| System      =
| Artery      =
| Vein        =
| Nerve       =
| Lymph       =
}}
'''Adipocytes''', also known as '''lipocytes''' and '''fat cells''', are the [[cell (biology)|cell]]s that primarily compose [[adipose tissue]], specialized in storing energy as [[fat]].<ref name="Birbrair 2298–2314">{{cite journal | vauthors = Birbrair A, Zhang T, Wang ZM, Messi ML, Enikolopov GN, Mintz A, Delbono O | title = Role of pericytes in skeletal muscle regeneration and fat accumulation | journal = Stem Cells and Development | volume = 22 | issue = 16 | pages = 2298–2314 | date = August 2013 | pmid = 23517218 | pmc = 3730538 | doi = 10.1089/scd.2012.0647 }}</ref> Adipocytes are derived from [[mesenchymal stem cell]]s which give rise to adipocytes through [[adipogenesis]].  In [[cell culture]], adipocyte progenitors can also form [[osteoblasts]], [[myocytes]] and other cell types.

There are two types of adipose tissue, [[white adipose tissue]] (WAT) and [[brown adipose tissue]] (BAT), which are also known as white and brown fat, respectively, and comprise two types of fat cells.

== Structure ==
===White fat cells===
[[File:Brown fat cell.jpg|thumb|224x224px|A 
brown fat cell.]]
[[File: Yellow adipose tissue in paraffin section - lipids washed out.jpg|thumb|Yellow adipose tissue in paraffin.]]
White fat cells contain a single large [[lipid droplet]] surrounded by a layer of
[[cytoplasm]], and are known as unilocular. The [[Cell nucleus|nucleus]] is flattened and pushed to the periphery. A typical fat cell is 0.1&nbsp;mm in diameter<ref name=":1">{{cite journal | vauthors = Ye RZ, Richard G, Gévry N, Tchernof A, Carpentier AC | title = Fat Cell Size: Measurement Methods, Pathophysiological Origins, and Relationships With Metabolic Dysregulations | journal = Endocrine Reviews | volume = 43 | issue = 1 | pages = 35–60 | date = January 2022 | pmid = 34100954 | pmc = 8755996 | doi = 10.1210/endrev/bnab018 }}</ref> with some being twice that size, and others half that size. However, these numerical estimates of fat cell size depend largely on the measurement method and the location of the adipose tissue.<ref name=":1" /> The fat stored is in a semi-liquid state, and is composed primarily of [[triglyceride]]s, and [[cholesteryl ester]]. White fat cells secrete many proteins acting as [[adipokine]]s such as [[resistin]], [[adiponectin]], [[leptin]] and [[apelin]]. An average human adult has 30 billion fat cells with a weight of 30&nbsp;lbs or 13.5&nbsp;kg. If a child or adolescent gains sufficient excess weight, fat cells may increase in absolute number until age twenty-four.<ref name = "Pool_2001" /> If an adult (who never was obese as a child or adolescent) gains excess weight, fat cells generally increase in size, not number, though there is some inconclusive evidence suggesting that the number of fat cells might also increase if the existing fat cells become large enough (as in particularly severe levels of obesity).<ref name = "Pool_2001" /> The number of fat cells is difficult to decrease through dietary intervention, though some evidence suggests that the number of fat cells can decrease if weight loss is maintained for a sufficiently long period of time (>1 year; though it is extremely difficult for people with larger and more numerous fat cells to maintain weight loss for that long a time).<ref name = "Pool_2001" />

A large meta-analysis has shown that white adipose tissue cell size is dependent on measurement methods, adipose tissue depots, age, and body mass index; for the same degree of obesity, increases in fat cell size were also associated with the dysregulations in glucose and  lipid metabolism.<ref name=":1" />

===Brown fat cells===

[[Brown adipose tissue|Brown fat cells]] are [[Polyhedron|polyhedral]] in shape. Brown fat is derived from dermatomyocyte cells. Unlike [[white fat]] cells, these cells have considerable cytoplasm, with several [[lipid]] droplets scattered throughout, and are known as multilocular cells. The nucleus is round and, although eccentrically located, it is not in the periphery of the cell. The brown color comes from the large quantity of [[mitochondria]]. Brown fat, also 
known as "baby fat," is used to generate heat.

===Marrow fat cells===
Marrow adipocytes are unilocular like white fat cells.  The [[marrow adipose tissue]] depot is poorly understood in terms of its physiologic function and relevance to bone health. Marrow adipose tissue expands in states of low bone density but additionally expands in the setting of obesity.<ref name=":0">{{cite journal | vauthors = Styner M, Pagnotti GM, McGrath C, Wu X, Sen B, Uzer G, Xie Z, Zong X, Styner MA, Rubin CT, Rubin J | display-authors = 6 | title = Exercise Decreases Marrow Adipose Tissue Through β-Oxidation in Obese Running Mice | journal = Journal of Bone and Mineral Research | volume = 32 | issue = 8 | pages = 1692–1702 | date = August 2017 | pmid = 28436105 | pmc = 5550355 | doi = 10.1002/jbmr.3159 }}</ref> Marrow adipose tissue response to exercise approximates that of [[white adipose tissue]].<ref name=":0" /><ref>{{cite journal | vauthors = Pagnotti GM, Styner M | title = Exercise Regulation of Marrow Adipose Tissue | journal = Frontiers in Endocrinology | volume = 7 | pages = 94 | date = 2016 | pmid = 27471493 | pmc = 4943947 | doi = 10.3389/fendo.2016.00094 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Styner M, Pagnotti GM, Galior K, Wu X, Thompson WR, Uzer G, Sen B, Xie Z, Horowitz MC, Styner MA, Rubin C, Rubin J | display-authors = 6 | title = Exercise Regulation of Marrow Fat in the Setting of PPARγ Agonist Treatment in Female C57BL/6 Mice | journal = Endocrinology | volume = 156 | issue = 8 | pages = 2753–2761 | date = August 2015 | pmid = 26052898 | pmc = 4511140 | doi = 10.1210/en.2015-1213 }}</ref><ref>{{cite journal | vauthors = Styner M, Thompson WR, Galior K, Uzer G, Wu X, Kadari S, Case N, Xie Z, Sen B, Romaine A, Pagnotti GM, Rubin CT, Styner MA, Horowitz MC, Rubin J | display-authors = 6 | title = Bone marrow fat accumulation accelerated by high fat diet is suppressed by exercise | journal = Bone | volume = 64 | pages = 39–46 | date = July 2014 | pmid = 24709686 | pmc = 4041821 | doi = 10.1016/j.bone.2014.03.044 }}</ref> Exercise reduces both adipocyte size as well as marrow adipose tissue volume, as quantified by [[MRI]] or [[X-ray microtomography|μCT imaging]] of bone stained with the lipid binder [[osmium]].

==Development==
[[File:Lipoblast features, annotated.png|thumb|[[Lipoblast]] features on [[histology]], [[H&E stain]].]]
'''Pre-adipocytes''' are undifferentiated [[fibroblast]]s that can be stimulated to form adipocytes. Studies have shed light into potential molecular mechanisms in the fate determination of pre-adipocytes although the exact lineage of adipocyte is still unclear.<ref name="Coskun_2010">{{cite journal | vauthors = Coskun H, Summerfield TL, Kniss DA, Friedman A | title = Mathematical modeling of preadipocyte fate determination | journal = Journal of Theoretical Biology | volume = 265 | issue = 1 | pages = 87–94 | date = July 2010 | pmid = 20385145 | doi = 10.1016/j.jtbi.2010.03.047 | bibcode = 2010JThBi.265...87C }}
*{{lay source |template=cite news |date=August 18, 2010 |title=Scientists closer to finding what causes the birth of a fat cell |url=https://www.sciencedaily.com/releases/2010/08/100816114835.htm |work=ScienceDaily}}</ref><ref name="coskun2010">{{cite journal | vauthors = Coskun H, Summerfield TL, Kniss DA, Friedman A | title = Mathematical modeling of preadipocyte fate determination | journal = Journal of Theoretical Biology | volume = 265 | issue = 1 | pages = 87–94 | date = July 2010 | pmid = 20385145 | doi = 10.1016/j.jtbi.2010.03.047 | bibcode = 2010JThBi.265...87C }}</ref> The variation of body fat distribution resulting from normal growth is influenced by nutritional and hormonal status dependent on intrinsic differences in cells found in each adipose depot.<ref name="pmid26054752">{{cite journal | vauthors = Fried SK, Lee MJ, Karastergiou K | title = Shaping fat distribution: New insights into the molecular determinants of depot- and sex-dependent adipose biology | journal = Obesity | volume = 23 | issue = 7 | pages = 1345–1352 | date = July 2015 | pmid = 26054752 | pmc = 4687449 | doi = 10.1002/oby.21133 | type = Review }}</ref>

[[Mesenchymal stem cell]]s can differentiate into adipocytes, [[connective tissue]], muscle or [[bone]].<ref name="Birbrair 2298–2314"/>

The precursor of the adult cell is termed a [[lipoblast]], and a tumor of this cell type is known as a [[lipoblastoma]].<ref name="pmid18528880">{{cite journal | vauthors = Hong R, Choi DY, Do NY, Lim SC | title = Fine-needle aspiration cytology of a lipoblastoma: a case report | journal = Diagnostic Cytopathology | volume = 36 | issue = 7 | pages = 508–511 | date = July 2008 | pmid = 18528880 | doi = 10.1002/dc.20826 | s2cid = 22668394 }}</ref>

== Function ==
===Cell turnover===

Fat cells in some mice have been shown to drop in count due to fasting and other properties were observed when exposed to cold.<ref>{{cite journal | vauthors = Ding H, Zheng S, Garcia-Ruiz D, Hou D, Wei Z, Liao Z, Li L, Zhang Y, Han X, Zen K, Zhang CY, Li J, Jiang X | display-authors = 6 | title = Fasting induces a subcutaneous-to-visceral fat switch mediated by microRNA-149-3p and suppression of PRDM16 | journal = Nature Communications | volume = 7 | pages = 11533 | date = May 2016 | pmid = 27240637 | pmc = 4895052 | doi = 10.1038/ncomms11533 | bibcode = 2016NatCo...711533D }}</ref>

If the adipocytes in the body reach their maximum capacity of fat, they may replicate to allow additional fat storage.

{{blockquote|Adult rats of various strains became obese when they were fed a highly palatable diet for several months. Analysis of their adipose tissue morphology revealed increases in both adipocyte size and number in most depots. Reintroduction of an ordinary [[chow diet]]<ref>{{cite journal | vauthors = Warden CH, Fisler JS | title = Comparisons of diets used in animal models of high-fat feeding | journal = Cell Metabolism | volume = 7 | issue = 4 | pages = 277 | date = April 2008 | pmid = 18396128 | pmc = 2394560 | doi = 10.1016/j.cmet.2008.03.014 | quote = Regular chow is composed of agricultural byproducts, such as ground wheat, corn, or oats, alfalfa and soybean meals, a protein source such as fish, and vegetable oil and is supplemented with minerals and vitamins. Thus, chow is a high fiber diet containing complex carbohydrates, with fats from a variety of vegetable sources. Chow is inexpensive to manufacture and is palatable to rodents. }}</ref> to such animals precipitated a period of weight loss during which only mean adipocyte size returned to normal. Adipocyte number remained at the elevated level achieved during the period of weight gain.<ref>{{cite journal | vauthors = Faust IM, Johnson PR, Stern JS, Hirsch J | title = Diet-induced adipocyte number increase in adult rats: a new model of obesity | journal = The American Journal of Physiology | volume = 235 | issue = 3 | pages = E279–E286 | date = September 1978 | pmid = 696822 | doi = 10.1152/ajpendo.1978.235.3.E279 | s2cid = 7744250 }}</ref>
|sign=|source=}}

According to some reports and textbooks, the number of adipocytes can increase in childhood and adolescence, though the amount is usually constant in adults. Individuals who become obese as adults, rather than as adolescents, have no more adipocytes than they had before.<ref name="ReferenceA">{{cite journal | vauthors = Spalding KL, Arner E, Westermark PO, Bernard S, Buchholz BA, Bergmann O, Blomqvist L, Hoffstedt J, Näslund E, Britton T, Concha H, Hassan M, Rydén M, Frisén J, Arner P | display-authors = 6 | title = Dynamics of fat cell turnover in humans | journal = Nature | volume = 453 | issue = 7196 | pages = 783–787 | date = June 2008 | pmid = 18454136 | doi = 10.1038/nature06902 | s2cid = 4431237 | bibcode = 2008Natur.453..783S }}</ref>

{{blockquote|People who have been fat since childhood generally have an inflated number of fat cells. People who become fat as adults may have no more fat cells than their lean peers, but their fat cells are larger. In general, people with an excess of fat cells find it harder to lose weight and keep it off than the obese who simply have enlarged fat cells.<ref name = "Pool_2001">{{cite book | vauthors = Pool R | title = Fat: fighting the obesity epidemic | publisher = Oxford University Press | location = Oxford [Oxfordshire] | year = 2001 | pages = [https://archive.org/details/fatfightingobesi00pool/page/68 68] | isbn = 978-0-19-511853-7 | url-access = registration | url = https://archive.org/details/fatfightingobesi00pool/page/68 }}</ref>
}}

Body fat cells have regional responses to the overfeeding that was studied in adult subjects. In the upper body, an increase of adipocyte size correlated with upper-body fat gain; however, the number of fat cells was not significantly changed. In contrast to the upper body fat cell response, the number of lower-body adipocytes did significantly increase during the course of experiment. Notably, there was no change in the size of the lower-body adipocytes.<ref>{{cite journal | vauthors = Tchoukalova YD, Votruba SB, Tchkonia T, Giorgadze N, Kirkland JL, Jensen MD | title = Regional differences in cellular mechanisms of adipose tissue gain with overfeeding | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 107 | issue = 42 | pages = 18226–18231 | date = October 2010 | pmid = 20921416 | pmc = 2964201 | doi = 10.1073/pnas.1005259107 | doi-access = free }}</ref>

Approximately 10% of fat cells are renewed annually at all adult ages and levels of body mass index without a significant increase in the overall number of adipocytes in adulthood.<ref name="ReferenceA"/>

===Adaptation===
[[Obesity]] is characterized by the expansion of fat mass, through adipocyte size increase ([[hypertrophy]]) and, to a lesser extent, cell proliferation ([[hyperplasia]]).<ref>{{cite journal | vauthors = Blüher M | title = Adipose tissue dysfunction in obesity | journal = Experimental and Clinical Endocrinology & Diabetes | volume = 117 | issue = 6 | pages = 241–250 | date = June 2009 | pmid = 19358089 | doi = 10.1055/s-0029-1192044 }}</ref><ref name=":1" /> In the [[Adipose tissue|fatty tissue]] of obese individuals, there is increased production of metabolism modulators, such as [[glycerol]], [[hormone]]s, [[macrophage]]-stimulating [[chemokine]]s, and [[Inflammatory cytokine|pro-inflammatory cytokines]], leading to the development of [[insulin resistance]].<ref>{{cite journal | vauthors = [[Steven Kahn (endocrinologist)|Kahn SE]], Hull RL, Utzschneider KM | title = Mechanisms linking obesity to insulin resistance and type 2 diabetes | journal = Nature | volume = 444 | issue = 7121 | pages = 840–846 | date = December 2006 | pmid = 17167471 | doi = 10.1038/nature05482 | s2cid = 120626 | bibcode = 2006Natur.444..840K }}</ref> Production of these modulators and the resulting [[pathogenesis]] of insulin resistance are probably caused by adipocytes as well as [[immune system]] macrophages that infiltrate the tissue.<ref>{{cite journal | vauthors = Bastard JP, Maachi M, Lagathu C, Kim MJ, Caron M, Vidal H, Capeau J, Feve B | display-authors = 6 | title = Recent advances in the relationship between obesity, inflammation, and insulin resistance | journal = European Cytokine Network | volume = 17 | issue = 1 | pages = 4–12 | date = March 2006 | pmid = 16613757 | url = https://pubmed.ncbi.nlm.nih.gov/16613757/ | quote = Several factors derived not only from adipocytes but also from infiltrated macrophages probably contribute to the pathogenesis of insulin resistance. }}</ref>

Fat production in adipocytes is strongly stimulated by [[insulin]]. By controlling the activity of the [[pyruvate dehydrogenase]] and the [[acetyl-CoA carboxylase]] enzymes, insulin promotes unsaturated [[fatty acid synthesis]]. It also promotes [[glucose uptake]] and induces [[SREBF1]], which activates the transcription of genes that stimulate [[lipogenesis]].<ref>{{cite journal | vauthors = Kahn BB, Flier JS | title = Obesity and insulin resistance | journal = The Journal of Clinical Investigation | volume = 106 | issue = 4 | pages = 473–481 | date = August 2000 | pmid = 10953022 | pmc = 380258 | doi = 10.1172/JCI10842 }}</ref>

[[SREBF1]] ([[sterol]] regulatory element-binding [[transcription factor]] 1) is a transcription factor synthesized as an inactive [[Protein precursor|precursor protein]] inserted into the [[Endoplasmic reticulum|endoplasmic reticulum (ER)]] membrane by two membrane-spanning [[Helix|helices]]. Also anchored in the ER membrane is [[SREBP cleavage activating protein|SCAP]] (SREBF-cleavage activating protein), which binds SREBF1. The SREBF1-SCAP complex is retained in the ER membrane by [[INSIG1]] (insulin-induced gene 1 protein). When sterol levels are depleted, INSIG1 releases SCAP and the SREBF1-SCAP complex can be sorted into transport [[Vesicle (biology and chemistry)|vesicles]] coated by the [[coatomer]] [[COPII]] that are exported to the [[Golgi apparatus]]. In the Golgi apparatus, SREBF1 is cleaved and released as a transcriptionally active mature protein. It is then free to [[Protein translocation|translocate]] to the [[Cell nucleus|nucleus]] and activate the expression of its target genes.<ref>{{cite journal | vauthors = Rawson RB | title = The SREBP pathway--insights from Insigs and insects | journal = Nature Reviews. Molecular Cell Biology | volume = 4 | issue = 8 | pages = 631–640 | date = August 2003 | pmid = 12923525 | doi = 10.1038/nrm1174 | s2cid = 20818196 }}</ref>

[[File:Proteolytic activation of SREBF-controlled lipid biosynthesis.jpg|thumb|Proteolytic activation of SREBF-controlled lipid biosynthesis.]]

Clinical studies have repeatedly shown that even though insulin resistance is usually associated with obesity, the membrane [[phospholipid]]s of the adipocytes of obese patients generally still show an increased degree of fatty acid unsaturation.<ref name="ReferenceB">{{cite journal | vauthors = Carobbio S, Hagen RM, Lelliott CJ, Slawik M, Medina-Gomez G, Tan CY, Sicard A, Atherton HJ, Barbarroja N, Bjursell M, Bohlooly-Y M, Virtue S, Tuthill A, Lefai E, Laville M, Wu T, Considine RV, Vidal H, Langin D, Oresic M, Tinahones FJ, Fernandez-Real JM, Griffin JL, Sethi JK, López M, Vidal-Puig A | display-authors = 6 | title = Adaptive changes of the Insig1/SREBP1/SCD1 set point help adipose tissue to cope with increased storage demands of obesity | journal = Diabetes | volume = 62 | issue = 11 | pages = 3697–3708 | date = November 2013 | pmid = 23919961 | pmc = 3806615 | doi = 10.2337/db12-1748 }}</ref> This seems to point to an adaptive mechanism that allows the adipocyte to maintain its functionality, despite the increased storage demands associated with obesity and insulin resistance.

A study conducted in 2013<ref name="ReferenceB"/> found that, while INSIG1 and SREBF1 [[Messenger RNA|mRNA]] expression was decreased in the adipose tissue of obese mice and humans, the amount of active SREBF1 was increased in comparison with normal mice and non-obese patients. This downregulation of INSIG1 expression combined with the increase of mature SREBF1 was also correlated with the maintenance of SREBF1-target gene expression. Hence, it appears that, by downregulating INSIG1, there is a resetting of the INSIG1/SREBF1 loop, allowing for the maintenance of active SREBF1 levels. This seems to help compensate for the anti-lipogenic effects of insulin resistance and thus preserve adipocyte fat storage abilities and availability of appropriate levels of fatty acid unsaturation in face of the nutritional pressures of obesity.

===Endocrine role===
Adipocytes can synthesize [[estrogen]]s from [[androgen]]s,<ref>{{cite journal | vauthors = Nelson LR, Bulun SE | title = Estrogen production and action | journal = Journal of the American Academy of Dermatology | volume = 45 | issue = 3 Suppl | pages = S116–S124 | date = September 2001 | pmid = 11511861 | doi = 10.1067/mjd.2001.117432 }}</ref> potentially being the reason why being [[underweight]] or [[overweight]] are risk factors for [[infertility]].<ref name=asrm-risks>{{cite web | title = FERTILITY FACT: Female Risks | publisher = American Society for Reproductive Medicine (ASRM) | url = http://www.protectyourfertility.com/femalerisks.html | archive-url = https://web.archive.org/web/20070922184324/http://www.protectyourfertility.com/femalerisks.html | url-status = dead | archive-date = 22 September 2007 }}</ref> Additionally, adipocytes are responsible for the production of the hormone [[leptin]]. Leptin is important in regulation of appetite and acts as a satiety factor.<ref>{{cite journal | vauthors = Klok MD, Jakobsdottir S, Drent ML | title = The role of leptin and ghrelin in the regulation of food intake and body weight in humans: a review | journal = Obesity Reviews | volume = 8 | issue = 1 | pages = 21–34 | date = January 2007 | pmid = 17212793 | doi = 10.1111/j.1467-789X.2006.00270.x | s2cid = 24266123 | doi-access = free }}</ref>

== See also ==
*[[List of human cell types derived from the germ layers]]

== References ==
{{reflist}}

== External links ==
*{{BUHistology|08201loa}} – "Connective Tissue: unilocular (white) adipocytes "
*{{BUHistology|04901lob}} – "Connective Tissue: multilocular (brown) adipocytes"

{{Connective tissue}}
{{Authority control}}

[[Category:Sequestering cells]]
[[Category:Human cells]]
[[Category:Connective tissue cells]]