White adipose tissue | |
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Details | |
Identifiers | |
Latin | textus adiposus albus |
MeSH | D052436 |
TH | H2.00.03.4.00002 |
FMA | 20117 |
Anatomical terminology |
White adipose tissue or white fat is one of the two types of adipose tissue found in mammals. The other kind is brown adipose tissue. White adipose tissue is composed of monolocular adipocytes.
In humans, the healthy amount of white adipose tissue varies with age, but composes between 6–25% of body weight in adult men and 14–35% in adult women. [1] [ additional citation(s) needed ]
Its cells contain a single large fat droplet, which forces the nucleus to be squeezed into a thin rim at the periphery. They have receptors for insulin, sex hormones, norepinephrine, and glucocorticoids.
White adipose tissue is used for energy storage. Upon release of insulin from the pancreas, white adipose cells' insulin receptors cause a dephosphorylation cascade that leads to the inactivation of hormone-sensitive lipase. It was previously thought that upon release of glucagon from the pancreas, glucagon receptors cause a phosphorylation cascade that activates hormone-sensitive lipase, causing the breakdown of the stored fat to fatty acids, which are exported into the blood and bound to albumin, and glycerol, which is exported into the blood freely. There is actually no evidence at present that glucagon has any effect on lipolysis in white adipose tissue. [2] Glucagon is now thought to act exclusively on the liver to trigger glycogenolysis and gluconeogenesis. [3] The trigger for this process in white adipose tissue is instead now thought to be adrenocorticotropic hormone, [4] [5] adrenaline [6] and noradrenaline [ citation needed ]. Fatty acids are taken up by muscle and cardiac tissue as a fuel source, and glycerol is taken up by the liver for gluconeogenesis.
White adipose tissue also acts as a thermal insulator, helping to maintain body temperature.
The hormone leptin is primarily manufactured in the adipocytes of white adipose tissue [7] which also produces another hormone, asprosin.
White adipose tissue is most abundant in mammals and its distribution greatly varies among different species. [8] Usually white adipose tissue can be found in two different locations of the body where it is stored: subcutaneous adipose tissue and intra-abdominal adipose tissue. Subcutaneous adipose tissue is directly underneath the skin, while the intra-abdominal adipose tissue surrounds the organs inside the abdomen such as intestine and kidneys. [8] The intra-abdominal adipose tissues covers the thoracic and abdominal cavity. The visceral adipose tissue is part of the intra-abdominal adipose tissue that surrounds the intestine for the most part. [8] White adipose tissue exists mostly as a single adipocytes in the subcutaneous tissue. [9]
In humans, white adipose tissue starts to develop during early to mid-gestation period. White adipose tissue consists of white adipocytes, which are the lipid storage cells. They are differentiated from undifferentiated preadipocytes through transcriptional cascade. This process is regulated by the nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ), a protein regulating gene involved in regulation of fatty acid storage and glucose metabolism and members of the CCAAT/enhancer-binding protein family, type of transcription factors that promotes gene expression. [10] PPARγ is required for both the adipogenesis and maintenance of the adipocytes.
White adipose tissue exists in various depots that may have different types of adipocytes. [8] That is, different depots in different locations have different intrinsic properties. This led to various theories to find the adipogenic lineage of the white adipose tissue depots. A hypothesis is that the precursors for the different types of adipocytes are mesenchymal stem cells which differentiates by the influence of specific gene expression into specialized white preadipocytes. Such genes are Shox2, En1, Tbx15, HoxC9, HoxC8, and HoxA5. [8] The study of the gene expression is important as they can be indicative of various health issues such as obesity related risk factors including diabetes and metabolic conditions.
Leptin, also known as obese protein, is a protein hormone predominantly made by adipocytes. Its primary role is likely to regulate long-term energy balance.
Glucagon is a peptide hormone, produced by alpha cells of the pancreas. It raises the concentration of glucose and fatty acids in the bloodstream and is considered to be the main catabolic hormone of the body. It is also used as a medication to treat a number of health conditions. Its effect is opposite to that of insulin, which lowers extracellular glucose. It is produced from proglucagon, encoded by the GCG gene.
Lipolysis is the metabolic pathway through which lipid triglycerides are hydrolyzed into a glycerol and free fatty acids. It is used to mobilize stored energy during fasting or exercise, and usually occurs in fat adipocytes. The most important regulatory hormone in lipolysis is insulin; lipolysis can only occur when insulin action falls to low levels, as occurs during fasting. Other hormones that affect lipolysis include leptin, glucagon, epinephrine, norepinephrine, growth hormone, atrial natriuretic peptide, brain natriuretic peptide, and cortisol.
Adipose tissue is a loose connective tissue composed mostly of adipocytes. It also contains the stromal vascular fraction (SVF) of cells including preadipocytes, fibroblasts, vascular endothelial cells and a variety of immune cells such as adipose tissue macrophages. Its main role is to store energy in the form of lipids, although it also cushions and insulates the body.
In the field of molecular biology, the peroxisome proliferator–activated receptors (PPARs) are a group of nuclear receptor proteins that function as transcription factors regulating the expression of genes. PPARs play essential roles in the regulation of cellular differentiation, development, and metabolism, and tumorigenesis of higher organisms.
Adipocytes, also known as lipocytes and fat cells, are the cells that primarily compose adipose tissue, specialized in storing energy as fat. Adipocytes are derived from mesenchymal stem cells which give rise to adipocytes through adipogenesis. In cell culture, adipocyte progenitors can also form osteoblasts, myocytes and other cell types.
Adiponectin is a protein hormone and adipokine, which is involved in regulating glucose levels and fatty acid breakdown. In humans, it is encoded by the ADIPOQ gene and is produced primarily in adipose tissue, but also in muscle and even in the brain.
Resistin also known as adipose tissue-specific secretory factor (ADSF) or C/EBP-epsilon-regulated myeloid-specific secreted cysteine-rich protein (XCP1) is a cysteine-rich peptide hormone derived from adipose tissue that in humans is encoded by the RETN gene.
In biochemistry, lipogenesis is the conversion of fatty acids and glycerol into fats, or a metabolic process through which acetyl-CoA is converted to triglyceride for storage in fat. Lipogenesis encompasses both fatty acid and triglyceride synthesis, with the latter being the process by which fatty acids are esterified to glycerol before being packaged into very-low-density lipoprotein (VLDL). Fatty acids are produced in the cytoplasm of cells by repeatedly adding two-carbon units to acetyl-CoA. Triacylglycerol synthesis, on the other hand, occurs in the endoplasmic reticulum membrane of cells by bonding three fatty acid molecules to a glycerol molecule. Both processes take place mainly in liver and adipose tissue. Nevertheless, it also occurs to some extent in other tissues such as the gut and kidney. A review on lipogenesis in the brain was published in 2008 by Lopez and Vidal-Puig. After being packaged into VLDL in the liver, the resulting lipoprotein is then secreted directly into the blood for delivery to peripheral tissues.
Perilipin, also known as lipid droplet-associated protein, perilipin 1, or PLIN, is a protein that, in humans, is encoded by the PLIN gene. The perilipins are a family of proteins that associate with the surface of lipid droplets. Phosphorylation of perilipin is essential for the mobilization of fats in adipose tissue.
Hormone-sensitive lipase (EC 3.1.1.79, HSL), also previously known as cholesteryl ester hydrolase (CEH), sometimes referred to as triacylglycerol lipase, is an enzyme that, in humans, is encoded by the LIPE gene, and catalyzes the following reaction:
3T3-L1 is a sub clonal cell line derived from the original 3T3 Swiss albino cell line of 1962. The 3T3 original cell line was isolated from a mouse embryo and propagated for this specific line of 3T3 cells is used to study adipose tissue-related diseases and dysfunctions. The 3T3-L1 Swiss subclone line has been widely utilized, since its development, due to its affinity for lipid droplet deposition in vitro. 3T3-L1 cells have a fibroblast-like morphology, but, under appropriate conditions, the cells differentiate into an adipocyte-like phenotype, providing an exemplar model for white adipocytes. 3T3-L1 cells can be utilized to study a number of cellular and molecular mechanisms related to insulin-resistance, obesity, and diabetes in vitro. Aside from its usages, this cell line is widely developed and can be purchased for continuous propagation for numerous research studies. 3T3-L1 cells of the adipocyte morphology increase the synthesis and accumulation of triglycerides and acquire the signet ring appearance of adipose cells. These cells are also sensitive to lipogenic and lipolytic hormones, as well as drugs, including epinephrine, isoproterenol, and insulin.
Adipose triglyceride lipase, also known as patatin-like phospholipase domain-containing protein 2 and ATGL, is an enzyme that in humans is encoded by the PNPLA2 gene. ATGL catalyses the first reaction of lipolysis, where triacylglycerols are hydrolysed to diacylglycerols.
Group XVI phospholipase A2 also commonly known as adipocyte phospholipase A2 (AdPLA) is an enzyme that in humans is encoded by the PLA2G16 gene. This enzyme has also been identified as PLA2G16, HRASLS3, HREV107, HREV107-3, MGC118754 or H-REV107-1 from studies on class II tumor suppression but not on its enzymatic properties. AdPLA is encoded by a 1.3 kilobase AdPLA messenger RNA and is an 18 kDa protein. It belongs to a superfamily of phospholipase A2 (PLA2) enzymes and is found primarily in adipose tissue. AdPLA regulates adipocyte lipolysis and release of fatty acids through a G-protein coupled pathway involving prostaglandin and EP3. It has also been reported to play a crucial role in the development of obesity in mouse models.
Adipose tissue is an endocrine organ that secretes numerous protein hormones, including leptin, adiponectin, and resistin. These hormones generally influence energy metabolism, which is of great interest to the understanding and treatment of type 2 diabetes and obesity.
Chemerin, also known as retinoic acid receptor responder protein 2 (RARRES2), tazarotene-induced gene 2 protein (TIG2), or RAR-responsive protein TIG2 is a protein that in humans is encoded by the RARRES2 gene.
Acquired generalized lipodystrophy (AGL), also known as Lawrence syndrome and Lawrence–Seip syndrome, is a rare skin condition that appears during childhood or adolescence, characterized by fat loss affecting large areas of the body, particularly the face, arms, and legs. There are four types of lipodystrophy based on its onset and areas affected: acquired or inherited, and generalized or partial. Both acquired or inherited lipodystrophy present as loss of adipose tissues, in the absence of nutritional deprivation. The near-total loss of subcutaneous adipose tissue is termed generalized lipodystrophy while the selective loss of adipose tissues is denoted as partial lipodystrophy. Thus, as the name suggests, AGL is a near-total deficiency of adipose tissues in the body that is developed later in life. It is an extremely rare disease with only about 100 cases reported worldwide. There are three main etiologies of AGL suspected: autoimmune, panniculitis-associated, or idiopathic. After its onset, the disease progresses over a few days, weeks, months, or even in years. Clinical presentations of AGL are similar to other lipodystrophies, including metabolic complications and hypoleptinemia. Treatments are also similar and mainly supportive for symptomatic alleviation. Although HIV- or drug-induced lipodystrophy are types of acquired lipodystrophy, their origins are very specific and distinct and hence are usually not discussed with AGL.
Adipogenesis is the formation of adipocytes from stem cells. It involves 2 phases, determination, and terminal differentiation. Determination is mesenchymal stem cells committing to the adipocyte precursor cells, also known as lipoblasts or preadipocytes which lose the potential to differentiate to other types of cells such as chondrocytes, myocytes, and osteoblasts. Terminal differentiation is that preadipocytes differentiate into mature adipocytes. Adipocytes can arise either from preadipocytes resident in adipose tissue, or from bone-marrow derived progenitor cells that migrate to adipose tissue.
Lipotoxicity is a metabolic syndrome that results from the accumulation of lipid intermediates in non-adipose tissue, leading to cellular dysfunction and death. The tissues normally affected include the kidneys, liver, heart and skeletal muscle. Lipotoxicity is believed to have a role in heart failure, obesity, and diabetes, and is estimated to affect approximately 25% of the adult American population.
Adipose tissue macrophages (ATMs) comprise resident macrophages present in adipose tissue. Besides adipocytes, adipose tissue contains the stromal vascular fraction (SVF) of cells that includes pre-adipocytes, fibroblasts, vascular endothelial cells, and a large variety of immune cells. The latter ones are composed of mast cells, eosinophils, B cells, T cells and macrophages. The number of macrophages within adipose tissue differs depending on the metabolic status. As discovered by Rudolph Leibel and Anthony Ferrante et al. in 2003 at Columbia University, the percentage of macrophages within adipose tissue ranges from 10% in lean mice and humans up to 50% in obese leptin deficient mice, and up to 40% in obese humans. ATMs comprise nearly 50% of all immune cells in normal conditions, suggesting an important role in supporting normal functioning of the adipose tissue. Increased number of adipose tissue macrophages may correlate with increased production of pro-inflammatory molecules and might therefore contribute to the pathophysiological consequences of obesity, although is becoming recognized that in healthy conditions tissue-resident macrophages actively support a variety of critical physiological functions in nearly all organs and tissues, including adipose tissue.