Adipocyte

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Adipocyte
Blausen 0012 AdiposeTissue.png
Illustration depicting white fat cells.
Adipocyte types.jpg
Morphology of three different classes of adipocytes
Details
Identifiers
Latin adipocytus
MeSH D017667
TH H2.00.03.0.01005
FMA 63880
Anatomical terms of microanatomy

Adipocytes, also known as lipocytes and fat cells, are the cells that primarily compose adipose tissue, specialized in storing energy as fat. [1] 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.

Contents

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

A brown fat cell. Brown fat cell.jpg
A brown fat cell.
Yellow adipose tissue in paraffin. Yellow adipose tissue in paraffin section - lipids washed out.jpg
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 nucleus is flattened and pushed to the periphery. A typical fat cell is 0.1 mm in diameter [2] 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. [2] The fat stored is in a semi-liquid state, and is composed primarily of triglycerides, and cholesteryl ester. White fat cells secrete many proteins acting as adipokines such as resistin, adiponectin, leptin and apelin. An average human adult has 30 billion fat cells with a weight of 30 lbs or 13.5 kg. If a child or adolescent gains sufficient excess weight, fat cells may increase in absolute number until age twenty-four. [3] 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). [3] 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). [3]

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. [2]

Brown fat cells

Brown fat cells are 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. [4] Marrow adipose tissue response to exercise approximates that of white adipose tissue. [4] [5] [6] [7] Exercise reduces both adipocyte size as well as marrow adipose tissue volume, as quantified by MRI or μCT imaging of bone stained with the lipid binder osmium.

Development

Lipoblast features on histology, H&E stain. Lipoblast features, annotated.png
Lipoblast features on histology, H&E stain.

Pre-adipocytes are undifferentiated fibroblasts 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. [8] [9] 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. [10]

Mesenchymal stem cells can differentiate into adipocytes, connective tissue, muscle or bone. [1]

The precursor of the adult cell is termed a lipoblast, and a tumor of this cell type is known as a lipoblastoma. [11]

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. [12]

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

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 [13] 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. [14]

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. [15]

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. [3]

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. [16]

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. [15]

Adaptation

Obesity is characterized by the expansion of fat mass, through adipocyte size increase (hypertrophy) and, to a lesser extent, cell proliferation (hyperplasia). [17] [2] In the fatty tissue of obese individuals, there is increased production of metabolism modulators, such as glycerol, hormones, macrophage-stimulating chemokines, and pro-inflammatory cytokines, leading to the development of insulin resistance. [18] 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. [19]

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. [20]

SREBF1 (sterol regulatory element-binding transcription factor 1) is a transcription factor synthesized as an inactive precursor protein inserted into the endoplasmic reticulum (ER) membrane by two membrane-spanning helices. Also anchored in the ER membrane is 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 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 translocate to the nucleus and activate the expression of its target genes. [21]

Proteolytic activation of SREBF-controlled lipid biosynthesis. Proteolytic activation of SREBF-controlled lipid biosynthesis.jpg
Proteolytic activation of SREBF-controlled lipid biosynthesis.

Clinical studies have repeatedly shown that even though insulin resistance is usually associated with obesity, the membrane phospholipids of the adipocytes of obese patients generally still show an increased degree of fatty acid unsaturation. [22] 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 [22] found that, while INSIG1 and SREBF1 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 estrogens from androgens, [23] potentially being the reason why being underweight or overweight are risk factors for infertility. [24] Additionally, adipocytes are responsible for the production of the hormone leptin. Leptin is important in regulation of appetite and acts as a satiety factor. [25]

See also

Related Research Articles

Insulin resistance (IR) is a pathological condition in which cells in insulin-sensitive tissues in the body fail to respond normally to the hormone insulin or downregulate insulin receptors in response to hyperinsulinemia.

<span class="mw-page-title-main">Abdominal obesity</span> Excess fat around the stomach and abdomen

Abdominal obesity, also known as central obesity and truncal obesity, is the human condition of an excessive concentration of visceral fat around the stomach and abdomen to such an extent that it is likely to harm its bearer's health. Abdominal obesity has been strongly linked to cardiovascular disease, Alzheimer's disease, and other metabolic and vascular diseases.

<span class="mw-page-title-main">Leptin</span> Hormone that inhibits hunger

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.

<span class="mw-page-title-main">Lipolysis</span> Metabolism involving breakdown of lipids

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.

<span class="mw-page-title-main">Brown adipose tissue</span> Type of adipose tissue

Brown adipose tissue (BAT) or brown fat makes up the adipose organ together with white adipose tissue. Brown adipose tissue is found in almost all mammals.

<span class="mw-page-title-main">Adipose tissue</span> Loose connective tissue composed mostly by adipocytes

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.

<span class="mw-page-title-main">Adiponectin</span> Mammalian protein found in Homo sapiens

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.

<span class="mw-page-title-main">Resistin</span> Mammalian protein found in Homo sapiens

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.

<span class="mw-page-title-main">Weight gain</span> Increase in a persons total body mass

Weight gain is an increase in body weight. This can involve an increase in muscle mass, fat deposits, excess fluids such as water or other factors. Weight gain can be a symptom of a serious medical condition.

The adipokines, or adipocytokines are cytokines secreted by adipose tissue. Some contribute to an obesity-related low-grade state of inflammation or to the development of metabolic syndrome, a constellation of diseases including, but not limited to, type 2 diabetes, cardiovascular disease and atherosclerosis. The first adipokine to be discovered was leptin in 1994. Since that time, hundreds of adipokines have been discovered.

<span class="mw-page-title-main">Perilipin-1</span> Protein in humans

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.

<span class="mw-page-title-main">White adipose tissue</span> Fatty tissue composed of white adipocytes

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.

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.

<span class="mw-page-title-main">Chemerin</span> Protein-coding gene in the species Homo sapiens

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.

<span class="mw-page-title-main">Lipotoxicity</span> Metabolic disorder in which lipids accumulate in non-fat 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.

<span class="mw-page-title-main">Perilipin-4</span> Protein-coding gene in the species Homo sapiens

Perilipin 4, also known as S3-12, is a protein that in humans is encoded by the PLIN4 gene on chromosome 19. It is highly expressed in white adipose tissue, with lower expression in heart, skeletal muscle, and brown adipose tissue. PLIN4 coats lipid droplets in adipocytes to protect them from lipases. The PLIN4 gene may be associated with insulin resistance and obesity risk.

Obesity is defined as an abnormal accumulation of body fat, usually 20% or more over an individual's ideal body weight. This is often described as a body mass index (BMI) over 30. However, BMI does not account for whether the excess weight is fat or muscle, and is not a measure of body composition. For most people, however, BMI is an indication used worldwide to estimate nutritional status. Obesity is usually the result of consuming more calories than the body needs and not expending that energy by doing exercise. There are genetic causes and hormonal disorders that cause people to gain significant amounts of weight but this is rare. People in the obese category are much more likely to suffer from fertility problems than people of normal healthy weight.

<span class="mw-page-title-main">Bone marrow adipose tissue</span>

Bone marrow adipose tissue (BMAT), sometimes referred to as marrow adipose tissue (MAT), is a type of fat deposit in bone marrow. It increases in states of low bone density, such as osteoporosis, anorexia nervosa/caloric restriction, skeletal unweighting such as that which occurs in space travel, and anti-diabetes therapies. BMAT decreases in anaemia, leukaemia, and hypertensive heart failure; in response to hormones such as oestrogen, leptin, and growth hormone; with exercise-induced weight loss or bariatric surgery; in response to chronic cold exposure; and in response to pharmacological agents such as bisphosphonates, teriparatide, and metformin.

<span class="mw-page-title-main">Pathophysiology of obesity</span> Physiological processes in obese people

Pathophysiology of obesity is the study of disordered physiological processes that cause, result from, or are otherwise associated with obesity. A number of possible pathophysiological mechanisms have been identified which may contribute in the development and maintenance of obesity.

References

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