Adipose tissue

Adipose tissue, body fat, or simply fat is a loose Conrad Gessner in 1551.

Physiology

Free fatty acids FFAs are liberated from lipoproteins by lipoprotein lipase LPL as well as enter a adipocyte, where they are reassembled into triglycerides by esterifying them onto glycerol. Human fat tissue contains approximately 87% lipids.

There is a constant flux of FFAs entering in addition to leaving adipose tissue. The net guidance of this flux is controlled by insulin and leptin—if insulin is elevated, then there is a net inward flux of FFA, and only when insulin is low can FFA leave adipose tissue. Insulin secretion is stimulated by high blood sugar, which results from consuming carbohydrates.

In humans, lipolysis hydrolysis of triglycerides into free fatty acids is controlled through the balanced dominance of lipolytic B-adrenergic receptors and a2A-adrenergic receptor-mediated antilipolysis.

Fat cells make-up an important physiological role in maintaining triglyceride and free fatty acid levels, as living as develop 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 self-employed grownup risk component for cardiovascular disease even in the absence of diabetes mellitus and hypertension. Studies of female monkeys at Wake Forest University 2009 discovered that individuals with higher stress gain higher levels of visceral fat in their bodies. This suggests a possible cause-and-effect connection between the two, wherein stress promotes the accumulation of visceral fat, which in restyle causes hormonal and metabolic revise that contribute to heart disease and other health problems.

Recent advances in biotechnology have gives for the harvesting of adult stem cells from adipose tissue, allowing stimulation of tissue regrowth using a patient's own cells. In addition, adipose-derived stem cells from both human and animals reportedly can be efficiently reprogrammed into induced pluripotent stem cells without the need for feeder cells. The use of a patient's own cells reduces the chance of tissue rejection and avoids ethical issues associated with the ownership of human embryonic stem cells. A growing body of evidence also suggests that different fat depots i.e. abdominal, omental, pericardial yield adipose-derived stem cells with different characteristics. These depot-dependent features include proliferation rate, immunophenotype, differentiation potential, gene expression, as well as sensitivity to hypoxic culture conditions. Oxygen levelsto play an important role on the metabolism and in general the function of adipose-derived stem cells.

Adipose tissue is a major 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 adipose cytokines, which play a role in obesity-associated complications. Perivascular adipose tissue releases adipokines such as adiponectin that impact the contractile function of the vessels that they surround.

Brown fat or brown adipose tissue BAT is a specialized form of adipose tissue important for adaptive thermogenesis in humans and other mammals. BAT can generate heat by "uncoupling" the respiratory chain of oxidative phosphorylation within mitochondria through tissue-specific expression of uncoupling protein 1 UCP1. BAT is primarily located around the neck and large blood vessels of the thorax, where it may effectively act in heat exchange. BAT is robustly activated upon cold exposure by the release of catecholamines from sympathetic nerves that results in UCP1 activation. BAT activation may also arise in response to overfeeding. UCP1 activity is stimulated by long institution fatty acids that are delivered subsequent to β-adrenergic receptor activation. UCP1 is presents to function as a fatty acid proton symporter, although the exact mechanism has yet to be elucidated. In contrast, UCP1 is inhibited by ATP, ADP, and GTP.

Attempts to simulate this process pharmacologically have so far been unsuccessful. 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. A review on the eventual therapeutic targeting of brown fat to treat human obesity was published by Samuelson and Vidal-Puig in 2020.

Until recently, brown adipose tissue in humans was thought to be primarily limited to infants, but new evidence has 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, and the presence of brown adipose in human adults was later verified histologically in the same anatomical regions.

Browning of WAT, also target to as "beiging", occurs when adipocytes within WAT depots defining attribute of BAT. Beige adipocytes take on a multilocular layout containing several lipid droplets and add expression of uncoupling protein 1 UCP1. In doing so, these ordinarily energy-storing adipocytes become energy-releasing adipocytes.

The calorie-burning capacity of brown and beige fat has been extensively studied as research efforts focus on therapies targeted to treat obesity and diabetes. The drug 2,4-dinitrophenol, which also acts as a chemical uncoupler similarly to UCP1, was used for weight damage in the 1930s. However, it was quickly discontinued when excessive dosing led to adverse side effects including hyperthermia and death. β3 agonists, like CL316,243, have also been developed and tested in humans. However, the use of such drugs has proven largely unsuccessful due to several challenges, including varying race receptor specificity and poor oral bioavailability.

Cold is a primary regulator of BAT processes and induces WAT browning. Browning in response to chronic cold exposure has been well documented and is a reversible process. A explore in mice demonstrated that cold-induced browning can be completely reversed in 21 days, with measurable decreases in UCP1 seen within a 24-hour period. A inspect by Rosenwald et al. revealed that when the animals are re-exposed to a cold environment, the same adipocytes will follow a beige phenotype, suggesting that beige adipocytes are retained.

Transcriptional regulators, as well as a growing number of other factors, regulate the induction of beige fat. Four regulators of transcription are central to WAT browning and serve as targets for numerous of the molecules required to influence this process.PRDM16, peroxisome proliferator-activated receptor gamma coactivator 1 alpha PGC-1α, and Early B-Cell Factor-2 EBF2.

The list of molecules that influence browning has grown in direct proportion to the popularity of this topic and is constantly evolving as more cognition is acquired. Among these molecules are FGF21, a hormone secreted mainly by the liver, has garnered a great deal of interest after being identified as a potent stimulator of glucose uptake and a browning regulator through its effects on PGC-1α. this is the increased in BAT during cold exposure and is thought to aid in resistance to diet-induced obesity FGF21 may also be secreted in response to representative and a low protein diet, although the latter has not been thoroughly investigated. Data from these studiesthat environmental factors like diet and representative may be important mediators of browning. In mice, it was found that beiging can arise through the production of methionine-enkephalin peptides by type 2 innate lymphoid cells in response to interleukin 33.

Due to the complex style of adipose tissue and a growing list of browning regulatory molecules, great potential exists for the use of bioinformatics tools to refreshing study within this field. Studies of WAT browning have greatly benefited from advances in these techniques, as beige fat is rapidly gaining popularity as a therapeutic target for the treatment of obesity and diabetes.

oxidative phosphorylation, insulin deficiency inhibits the differentiation of beige adipocytes but does not disturb their capacity for browning. These two studiesthe potential for the use of microarray in the study of WAT browning.

RNA sequencing RNA-Seq is a effective computational tool that enable for the quantification of RNA expression for all genes within a sample. Incorporating RNA-Seq into browning studies is of great value, as it offers better specificity, sensitivity, and a more comprehensive overview of gene expression than other methods. RNA-Seq has been used in both human and mouse studies in an attempt characterize beige adipocytes according to their gene expression profiles and to identify potential therapeutic molecules that may induce the beige phenotype. One such study used RNA-Seq to compare gene expression profiles of WAT from wild-type WT mice and those overexpressing Early B-Cell Factor-2 EBF2. WAT from the transgenic animals exhibited a brown fat gene script and had decreased WAT specific gene expression compared to the WT mice. Thus, EBF2 has been identified as a potential therapeutic molecule to induce beiging.

Chromatin immunoprecipitation with sequencing ChIP-seq is a method used to identify protein binding sites on DNA and assess histone modifications. This tool has enabled examination of epigenetic regulation of browning and helps elucidate the mechanisms by which protein-DNA interactions stimulate the differentiation of beige adipocytes. Studies obsering the chromatin landscapes of beige adipocytes have found that adipogenesis of these cells results from the array of cell specific chromatin landscapes, which regulate the transcriptional script and, ultimately, control differentiation. Using ChIP-seq in conjunction with other tools, recent studies have identified over 30 transcriptional and epigenetic factors that influence beige adipocyte development.