PPAR-gamma
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PPAR-gamma
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 t ...
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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 γ ...
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Nuclear Receptor
In the field of molecular biology, nuclear receptors are a class of proteins responsible for sensing steroids, thyroid hormones, vitamins, and certain other molecules. These receptors work with other proteins to regulate the expression of specific genes thereby controlling the development, homeostasis, and 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—a molecule that affects the receptor's behavior. Ligand binding to a nuclear receptor results in a conformational change activating the receptor. The result is up- or down-regulation of gene expression. A unique property of nuclear receptors that differentiates them from other classes of receptors is their direct control of genomic DNA. Nuclear receptors play key roles in both embryonic development a ...
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FGF21
Fibroblast growth factor 21 is a liver-secreted peptide hormone that in humans is encoded by the ''FGF21'' gene. Together with FGF19 (FGF15 in rodents) and FGF23, this protein is a member of the endocrine subgroup within the fibroblast growth factor (FGF) family. FGF21 is a potent, extracellularly acting metabolic regulator, whose action was discovered through ''in vitro'' phenotypic screeninig and diet manipulation studies in rodents., unlike canonical growth-stimulating FGFs known to stimulate mitosis, differentiation and angiogenesis in their target tissues, FGF21 exerts its action by activating FGF21 receptors located in the cell membrane of target cells. Each FGF21 receptor is composed of a transmembrane FGF receptor protein (either FGFR1, FGFR2 or FGFR3), and its complexing co-receptor β-Klotho. Loss of β-Klotho abolishes all effects of FGF21 ''in vitro'' and ''in vivo''. In addition to its action as a hormone, FGF21 may be able to act in an ''autocrine'' fashion (ty ...
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Peroxisome Proliferator-activated Receptor Alpha
Peroxisome proliferator-activated receptor alpha (PPAR-α), also known as NR1C1 (nuclear receptor subfamily 1, group C, member 1), is a nuclear receptor protein functioning as a transcription factor that in humans is encoded by the ''PPARA'' gene. Together with peroxisome proliferator-activated receptor delta and peroxisome proliferator-activated receptor gamma, PPAR-alpha is part of the subfamily of peroxisome proliferator-activated receptors. It was the first member of the PPAR family to be cloned in 1990 by Stephen Green and has been identified as the nuclear receptor for a diverse class of rodent Liver, hepatocarcinogens that causes proliferation of peroxisomes. Expression PPAR-α is primarily activated through ligand binding. Endogenous ligands include fatty acids such as arachidonic acid as well as other polyunsaturated fatty acids and various fatty acid-derived compounds such as certain members of the 15-hydroxyicosatetraenoic acid, 15-hydroxyeicosatetraenoic acid family ...
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Polyunsaturated Fatty Acids
Polyunsaturated fatty acids (PUFAs) are fatty acids that contain more than one double bond in their backbone. This class includes many important compounds, such as essential fatty acids and those that give drying oils their characteristic property. Polyunsaturated fatty acids can be classified in various groups by their chemical structure: * methylene-interrupted polyenes * conjugated fatty acids * other PUFAs Based on the length of their carbon backbone, they are sometimes classified in two groups: * short chain polyunsaturated fatty acids (SC-PUFA), with 18 carbon atoms * long-chain polyunsaturated fatty acids (LC-PUFA) with 20 or more carbon atoms Dietary sources Types Methylene-interrupted polyenes These fatty acids have 2 or more ''cis'' double bonds that are separated from each other by a single methylene bridge (--). This form is also sometimes called a ''divinylmethane pattern''. The essential fatty acids are all omega-3 and -6 methylene-interrupted fatty ac ...
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ABCA1
ATP-binding cassette transporter ABCA1 (member 1 of human transporter sub-family ABCA), also known as the ''cholesterol efflux regulatory protein'' (CERP) is a protein which in humans is encoded by the ''ABCA1'' gene. This transporter is a major regulator of cellular cholesterol and phospholipid homeostasis. Tangier disease It was discovered that a mutation in the ABCA1 protein is responsible for causing Tangier disease by several groups in 1998. Gerd Schmitz's group in Germany and Michael Hayden's group in British Columbia were using standard genetics techniques and DNA from family pedigrees to locate the mutation. Richard Lawn's group at CV Therapeutics in Palo Alto, CA used cDNA microarrays, which were relatively new at the time, to assess gene expression profiles from cell lines created from normal and affected individuals. They showed cell lines from patients with Tangier's disease showed differential regulation of the ABCA1 gene. Subsequent sequencing of the gene identifie ...
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Reverse Cholesterol Transport
Reverse cholesterol transport is a multi-step process resulting in the net movement of cholesterol from peripheral tissues back to the liver first via entering the lymphatic system, then the bloodstream. Cholesterol from non-hepatic peripheral tissues is transferred to HDL by the ABCA1 (ATP-binding cassette transporter). Apolipoprotein A1 (ApoA-1), the major protein component of HDL, acts as an acceptor, and the phospholipid component of HDL acts as a sink for the mobilised cholesterol. The cholesterol is converted to cholesteryl esters by the enzyme LCAT ( lecithin-cholesterol acyltransferase). The cholesteryl esters can be transferred, with the help of CETP ( cholesterylester transfer protein) in exchange for triglycerides, to other lipoproteins (such as LDL and VLDL), and these lipoproteins can be taken up by secreting unesterified cholesterol into the bile or by converting cholesterol to bile acids. Adiponectin induces ABCA1-mediated reverse cholesterol transport from macrop ...
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Liver X Receptor
The liver X receptor (LXR) is a member of the nuclear receptor family of transcription factors and is closely related to nuclear receptors such as the PPARs, FXR and RXR. Liver X receptors (LXRs) are important regulators of cholesterol, fatty acid, and glucose homeostasis. LXRs were earlier classified as orphan nuclear receptors, however, upon discovery of endogenous oxysterols as ligands they were subsequently deorphanized. Two isoforms of LXR have been identified and are referred to as LXRα and LXRβ. The liver X receptors are classified into subfamily 1 (thyroid hormone receptor-like) of the nuclear receptor superfamily, and are given the nuclear receptor nomenclature symbols NR1H3 (LXRα) and NR1H2 (LXRβ) respectively. LXRα and LXRβ were discovered separately between 1994-1995. LXRα isoform was independently identified by two groups and initially named RLD-1 and LXR, whereas four groups identified the LXRβ isoform and called it UR, NER, OR-1, and RIP-15. The h ...
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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, muscles, an ...
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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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