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PPARγ
Peroxisome proliferator- activated receptor gamma (PPAR-γ or PPARG), also known as the glitazone reverse insulin resistance receptor, or NR1C3 (nuclear receptor subfamily 1, group C, member 3) is a type II nuclear receptor functioning as a transcription factor that in humans is encoded by the ''PPARG'' gene. Tissue distribution PPARG is mainly present in adipose tissue, colon and macrophages. Two isoforms of PPARG are detected in the human and in the mouse: PPAR-γ1 (found in nearly all tissues except muscle) and PPAR-γ2 (mostly found in adipose tissue and the intestine). Gene expression This gene encodes a member of the peroxisome proliferator-activated receptor (PPAR) subfamily of nuclear receptors. PPARs form heterodimers with retinoid X receptors (RXRs) and these heterodimers regulate transcription of various genes. Three subtypes of PPARs are known: PPAR-alpha, PPAR-delta, and PPAR-gamma. The protein encoded by this gene is PPAR-gamma and is a regulator of adipocyte ...
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Adipogenesis
Adipogenesis is the formation of adipocytes (fat cells) 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 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. Introduction Adipocytes play a vital role in energy homeostasis and process the largest energy reserve as triglycerol in the body of animals. Adipocytes stay in a dynamic state, they start expanding when the energy intake is higher than the expenditure and undergo mobilization when the energy expenditure exceeds the intake. This process is highly regulated by counter regulatory hormones ...
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Peroxisome Proliferator-activated Receptor
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 (carbohydrate, lipid, protein), and tumorigenesis of higher organisms. Nomenclature and tissue distribution Three types of PPARs have been identified: alpha, gamma, and delta (beta): * α (alpha) - expressed in liver, kidney, heart, muscle, adipose tissue, and others * β/δ (beta/delta) - expressed in many tissues, especially in brain, adipose tissue, and skin * γ (gamma) - although transcribed by the same gene, this PPAR, by way of alternative splicing, is expressed in three forms: ** γ1 - expressed in virtually all tissues, including heart, muscle, colon, kidney, pancreas, and spleen ** γ2 - expressed mainly in adipose tissue; it is 30 amino acids longer than Π...
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Adipose Tissue
Adipose tissue, body fat, or simply fat is a loose connective tissue composed mostly of adipocytes. In addition to adipocytes, adipose tissue 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. Adipose tissue is derived from preadipocytes. Its main role is to store energy in the form of lipids, although it also cushions and insulates the body. Far from being hormonally inert, adipose tissue has, in recent years, been recognized as a major endocrine organ, as it produces hormones such as leptin, estrogen, resistin, and cytokines (especially TNFα). In obesity, adipose tissue is also implicated in the chronic release of pro-inflammatory markers known as adipokines, which are responsible for the development of metabolic syndrome, a constellation of diseases including, but not limited to, type 2 diabetes, cardiovascular disease and atheroscler ...
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Nuclear Receptor
In the field of molecular biology, nuclear receptors are a class of proteins responsible for sensing steroid hormone, steroids, thyroid hormone, thyroid hormones, vitamins, and certain other molecules. These receptors work with other proteins to regulate the gene expression, expression of specific genes thereby controlling the developmental biology, development, Homeostasis#Overview, homeostasis, and metabolism#Regulation and control, metabolism of the organism. Nuclear receptors bind directly to DNA regulating the expression of adjacent genes; hence these receptors are classified as transcription factors. The regulation of gene expression by nuclear receptors often occurs in the presence of a ligand (biochemistry), ligand—a molecule that affects the receptor's behavior. Ligand binding to a nuclear receptor results in a Conformational isomerism, conformational change activating the receptor. The result is Regulation of gene expression#Up-regulation and down-regulation, up- o ...
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15-hydroxyicosatetraenoic Acid
15-Hydroxyeicosatetraenoic acid (also termed 15-HETE, 15(''S'')-HETE, and 15''S''-HETE) is an eicosanoid, i.e. a metabolite of arachidonic acid. Various cell types metabolize arachidonic acid to 15(''S'')-hydroperoxyeicosatetraenoic acid (15(''S'')-HpETE). This initial hydroperoxide product is extremely short-lived in cells: if not otherwise metabolized, it is rapidly reduced to 15''(S)''-HETE. Both of these metabolites, depending on the cell type which forms them, can be further metabolized to 15-oxo-eicosatetraenoic acid (15-oxo-ETE), 5''S'',15''S''-dihydroxy-eicosatetraenoic acid (5(''S''),15(''S'')-diHETE), 5-oxo-15(''S'')-hydroxyeicosatetraenoic acid (5-oxo-15(''S'')-HETE, a subset of specialized pro-resolving mediators viz., the lipoxins, a class of pro-inflammatory mediators, the eoxins, and other products that have less well-defined activities and functions. Thus, 15(''S'')-HETE and 15(''S'')-HpETE, in addition to having intrinsic biological activities, are key precursors ...
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Adipocyte
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. 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 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 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. The fat stored i ...
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Cannabinoid
Cannabinoids () are several structural classes of compounds found in the cannabis plant primarily and most animal organisms (although insects lack such receptors) or as synthetic compounds. The most notable cannabinoid is the phytocannabinoid tetrahydrocannabinol (THC) (delta-9-THC), the primary intoxicating compound in cannabis. Cannabidiol (CBD) is a major constituent of temperate Cannabis plants and a minor constituent in tropical varieties. At least 113 distinct phytocannabinoids have been isolated from cannabis, although only four (i.e., THCA, CBDA, CBCA and their common precursor CBGA) have been demonstrated to have a biogenetic origin. It was reported in 2020 that phytocannabinoids can be found in other plants such as rhododendron, licorice and liverwort, and earlier in Echinacea. Phytocannabinoids are multi-ring phenolic compounds structurally related to THC, but endocannabinoids are fatty acid derivatives. Nonclassical synthetic cannabinoids (cannabimimetics) include ami ...
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Tetrahydrocannabinol
Tetrahydrocannabinol (THC) is the principal psychoactive constituent of cannabis and one of at least 113 total cannabinoids identified on the plant. Although the chemical formula for THC (C21H30O2) describes multiple isomers, the term ''THC'' usually refers to the Delta-9-THC isomer with chemical name (−)-''trans''-Δ9-tetrahydrocannabinol. THC is a lipid found in cannabis and, like most pharmacologically active secondary metabolites of plants, it is assumed to be involved in the plant's evolutionary adaptation, putatively against insect predation, ultraviolet light, and environmental stress. THC was first discovered and isolated by Israeli chemist Raphael Mechoulam in Israel in 1964. It was found that, when smoked, THC is absorbed into the bloodstream and travels to the brain, attaching itself to endocannabinoid receptors located in the cerebral cortex, cerebellum, and basal ganglia. These are the parts of the brain responsible for thinking, memory, pleasure, coordi ...
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Macrophage Polarization
Macrophage polarization is a process by which macrophages adopt different functional programs in response to the signals from their microenvironment. This ability is connected to their multiple roles in the organism: they are powerful effector cells of the innate immune system, but also important in removal of cellular debris, embryonic development and tissue repair. By simplified classification, macrophage phenotype has been divided into 2 groups: M1 (classically activated macrophages) and M2 (alternatively activated macrophages). This broad classification was based on ''in vitro'' studies, in which cultured macrophages were treated with molecules that stimulated their phenotype switching to a particular state. In addition to chemical stimulation, it has been shown that the stiffness of the underlying substrate a macrophage is grown on can direct polarization state, functional roles and migration mode. A continuum of M1-M2 polarization may arise even in the absence of polarizing cyt ...
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Arachidonic Acid
Arachidonic acid (AA, sometimes ARA) is a polyunsaturated omega-6 fatty acid 20:4(ω-6), or 20:4(5,8,11,14). It is structurally related to the saturated arachidic acid found in cupuaçu butter. Its name derives from the New Latin word ''arachis'' (peanut), but peanut oil does not contain any arachidonic acid. Chemistry In chemical structure, arachidonic acid is a carboxylic acid with a 20-carbon chain and four '' cis''- double bonds; the first double bond is located at the sixth carbon from the omega end. Some chemistry sources define 'arachidonic acid' to designate any of the eicosatetraenoic acids. However, almost all writings in biology, medicine, and nutrition limit the term to ''all cis''-5,8,11,14-eicosatetraenoic acid. Biology Arachidonic acid is a polyunsaturated fatty acid present in the phospholipids (especially phosphatidylethanolamine, phosphatidylcholine, and phosphatidylinositides) of membranes of the body's cells, and is abundant in the brain, muscl ...
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11-Nor-9-carboxy-THC
11-Nor-9-carboxy-Δ9-tetrahydrocannabinol (11-COOH-THC or THC-COOH), often referred to as 11-nor-9-carboxy-THC or THC-11-oic acid, is the main secondary metabolite of tetrahydrocannabinol (THC) which is formed in the body after cannabis is consumed. Metabolism and detection 11-COOH-THC is formed in the body by oxidation of the active metabolite 11-hydroxy-THC (11-OH-THC) by liver enzymes. It is then metabolized further by conjugation with glucuronide, forming a water-soluble congener which can be more easily excreted by the body. 11-COOH-THC has a long half-life in the body of up to several days (or even weeks in very heavy users), making it the main metabolite tested for blood or urine testing for cannabis use. More selective tests are able to distinguish between 11-OH-THC and 11-COOH-THC, which can help determine how recently cannabis was consumed; if only 11-COOH-THC is present then cannabis was used some time ago and any impairment in cognitive ability or motor function wi ...
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