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Monogenic Obesity
Monogenic obesity is excess weight caused by a mutation in a single gene, as opposed to syndromic obesity not tied to a single gene variation and most obesity, which is caused by multiple genetic and environmental risk factors. Monogenetic obesity mostly affects the hypothalamus and leptin–melanocortin system (see hypothalamic obesity). However, it accounts for less than 5 percent of severe obesity cases. Known mutations leading to monogenetic obesity include: *Leptin deficiency *Leptin receptor deficiency * Melanocortin-4 receptor (MC4R) *Proopiomelanocortin (POMC *Prohormone convertase 1/3 (PC1/3) *SIM1 Single-minded homolog 1, also known as class E basic helix-loop-helix protein 14 (bHLHe14), is a protein that in humans is encoded by the ''SIM1'' gene. Function SIM1 and SIM2 genes are homologs of ''Drosophila melanogaster'' single-minded (sim), ... * BDNF * NTRK2 References {{Obesity Classification of obesity ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Syndromic Obesity
Syndromic obesity (SO) refers to obesity when it occurs as part of a syndrome, often along with intellectual disability. Often syndromic obesity is mediated by abnormal development of the hypothalamus (see hypothalamic obesity). Known types of syndromic obesity include some types of monogenic obesity and: *Prader Willi syndrome *Bardet-Biedl syndrome *Alstrom syndrome *16p11.2 deletion syndrome References {{reflist Syndromes with obesity ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Hypothalamus
The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamus is located below the thalamus and is part of the limbic system. In the terminology of neuroanatomy, it forms the ventral part of the diencephalon. All vertebrate brains contain a hypothalamus. In humans, it is the size of an almond. The hypothalamus is responsible for regulating certain metabolic processes and other activities of the autonomic nervous system. It synthesizes and secretes certain neurohormones, called releasing hormones or hypothalamic hormones, and these in turn stimulate or inhibit the secretion of hormones from the pituitary gland. The hypothalamus controls body temperature, hunger, important aspects of parenting and maternal attachment behaviours, thirst, fatigue, sleep, and circadian rhythms. Structure T ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Hypothalamic Obesity
Hypothalamic obesity (abbreviated HO or HyOb) is a rare condition that can be congenital or acquired. Congenital causes include Prader-Willi syndrome and mutations of LEP (leptin gene), LEPR, POMC, MC4R, and CART. It can also result from injuries to the hypothalamus either from trauma, therapeutic radiation, brain surgery, and especially craniopharyngioma and its treatments. Possible treatments include bariatric surgery and melanocortin 4 receptor agonists such as setmelanotide Setmelanotide, sold under the brand name Imcivree, is a medication used for the treatment of genetic obesity caused by a rare single-gene mutation. The most common side effects include injection site reactions, skin hyperpigmentation (skin patc .... References {{Obesity Risk factors for obesity Hypothalamus disorders Classification of obesity ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Leptin
Leptin (from Ancient Greek, Greek λεπτός ''leptos'', "thin" or "light" or "small") is a hormone predominantly made by adipose cells and enterocytes in the small intestine that helps to regulate Energy homeostasis, energy balance by inhibiting Hunger (motivational state), hunger, which in turn diminishes fat storage in adipocytes. Leptin is coded for by the ''LEP'' gene. Leptin acts on cell receptors in the arcuate nucleus, arcuate and Ventromedial nucleus of the hypothalamus, ventromedial nuclei, as well as other parts of the hypothalamus and Dopamine, dopaminergic neurons of the ventral tegmental area, consequently mediating Eating, feeding. Although regulation of fat stores is deemed to be the primary function of leptin, it also plays a role in other physiological processes, as evidenced by its many sites of synthesis other than fat cells, and the many cell types beyond hypothalamic cells that have leptin receptors. Many of these additional functions are yet to be fully ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Leptin Receptor
Leptin receptor, also known as LEP-R or OB-R, is a type I cytokine receptor, a protein that in humans is encoded by the ''LEPR'' gene. LEP-R functions as a receptor for the fat cell-specific hormone leptin. LEP-R has also been designated as CD295 (cluster of differentiation 295). Its location is the cell membrane, and it has extracellular, trans-membrane and intracellular sections (''protein regions''). History The Leptin Receptor was discovered in 1995 by Louis Tartaglia and his colleagues at Millennium Pharmaceuticals. This same team demonstrated the leptin receptor was expressed by the mouse db gene. Furthermore, in 1996, after co-discovering the Leptin gene with Jeffrey Friedman et al. in 1994, (which involved a reverse genetic/positional cloning strategy to clone ''ob'' and ''db)'', Rudolph Leibel, working with collaborators also at Millennium Pharmaceuticals and colleague Streamson Chua, confirmed cloning of the leptin receptor by demonstrating that an apparent leptin rece ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Melanocortin-4 Receptor
Melanocortin 4 receptor (MC4R) is a melanocortin receptor that in humans is encoded by the gene. It encodes the MC4R protein, a G protein-coupled receptor (GPCR) that binds α-melanocyte stimulating hormone (α-MSH). In mouse models, MC4 receptors have been found to be involved in feeding behaviour, the regulation of metabolism, sexual behaviour, and male erectile function. Clinical significance In 2009, two very large genome-wide association studies of body mass index (BMI) confirmed the association of variants about 150 kilobases downstream of the ''MC4R'' gene with insulin resistance, obesity, and other anthropometric traits. ''MC4R'' may also have clinical utility as a biomarker for predicting individual susceptibility to drug-induced adverse effects causing weight gain and related metabolic abnormalities. Another GWAS performed in 2012 identified twenty SNPs located ~190 Kb downstream of ''MC4R'' in association with severe antipsychotic-induced weight gain. This ''loc ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Proopiomelanocortin
Pro-opiomelanocortin (POMC) is a precursor polypeptide with 241 amino acid residues. POMC is synthesized in corticotrophs of the anterior pituitary from the 267-amino-acid-long polypeptide precursor pre-pro-opiomelanocortin (pre-POMC), by the removal of a 26-amino-acid-long signal peptide sequence during translation. POMC is part of the central melanocortin system. Function POMC is cut (cleaved) to give rise to multiple peptide hormones. Each of these peptides is packaged in large dense-core vesicles that are released from the cells by exocytosis in response to appropriate stimulation: * α-MSH produced by neurons in the ventromedial nucleus has important roles in the regulation of appetite (POMC neuron stimulation results in satiety.) and sexual behavior, while α-MSH secreted from the intermediate lobe of the pituitary regulates the movement of melanin produced from melanocytes in skin. * ACTH is a peptide hormone that regulates the secretion of mainly glucocorticoids from ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Prohormone Convertase 1
Proprotein convertase 1, also known as prohormone convertase, prohormone convertase 3, or neuroendocrine convertase 1 and often abbreviated as PC1/3 is an enzyme that in humans is encoded by the ''PCSK1'' gene. PCSK1 and PCSK2 differentially cleave proopiomelanocortin and they act together to process proinsulin and proglucagon in pancreatic islets. Function PC1/3 is an enzyme that performs the proteolytic cleavage of prohormones to their intermediate (or sometimes completely cleaved) forms. It is present only in neuroendocrine cells such as brain, pituitary and adrenal, and most often cleaves after a pair of basic residues within prohormones but can occasionally cleave after a single arginine. It binds to a protein known as proSAAS, which also represents its endogenous inhibitor. PC1 is synthesized as a 99 kDa proform quickly converted to an 87 kDa major active form, which itself is nearly completely cleaved to a 66 kDa active form within neuroendocrine cells. Proprotein conve ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
SIM1
Single-minded homolog 1, also known as class E basic helix-loop-helix protein 14 (bHLHe14), is a protein that in humans is encoded by the ''SIM1'' gene. Function SIM1 and SIM2 genes are homologs of ''Drosophila melanogaster'' single-minded (sim), so named because cells in the midline of the sim mutant embryo fail to properly develop and eventually die, and thus the paired longitudinal axon bundles that span the anterior-posterior axis of the embryo (analogous to the embryo's spinal cord) are collapsed into a "single" rudimentary axon bundle at the midline. SIM is a basic helix-loop-helix-PAS domain transcription factor that regulates gene expression in the midline cells. Because the sim gene plays an important role in Drosophila development and has peak levels of expression during the period of neurogenesis, it was proposed that the human SIM2 gene, which resides in a critical region of chromosome 21, is a candidate for involvement in certain dysmorphic features (particularly fac ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
BDNF
Brain-derived neurotrophic factor (BDNF), or abrineurin, is a protein found in the and the periphery. that, in humans, is encoded by the ''BDNF'' gene. BDNF is a member of the neurotrophin family of growth factors, which are related to the canonical nerve growth factor (NGF), a family which also includes NT-3 and NT-4/NT-5. Neurotrophic factors are found in the brain and the periphery. BDNF was first isolated from a pig brain in 1982 by Yves-Alain Barde and Hans Thoenen. BDNF activates the TrkB tyrosine kinase receptor. Function BDNF acts on certain neurons of the central nervous system and the peripheral nervous system expressing TrkB, helping to support survival of existing neurons, and encouraging growth and differentiation of new neurons and synapses. In the brain it is active in the hippocampus, cortex, and basal forebrain—areas vital to learning, memory, and higher thinking. BDNF is also expressed in the retina, kidneys, prostate, motor neurons, and skeletal mu ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
NTRK2
Tropomyosin receptor kinase B (TrkB), also known as tyrosine receptor kinase B, or BDNF/NT-3 growth factors receptor or neurotrophic tyrosine kinase, receptor, type 2 is a protein that in humans is encoded by the ''NTRK2'' gene. TrkB is a receptor for brain-derived neurotrophic factor (BDNF). Standard pronunciation is "track bee". Function Tropomyosin receptor kinase B is the high affinity catalytic receptor for several "neurotrophins", which are small protein growth factors that induce the survival and differentiation of distinct cell populations. The neurotrophins that activate TrkB are: BDNF (Brain Derived Neurotrophic Factor), neurotrophin-4 (NT-4), and neurotrophin-3 (NT-3).> As such, TrkB mediates the multiple effects of these neurotrophic factors, which includes neuronal differentiation and survival. Research has shown that activation of the TrkB receptor can lead to down regulation of the KCC2 chloride transporter in cells of the CNS. Except for the role of the pat ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
