Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Single nucleotide polymorphism (SNP) near certain genes revealed association of FAT(fat mass and obesity-associated gene), MC4R (melanocortin 4 receptor gene), and other genes with obesity. Participation of the FAT expression products in the regulation of energy balance remains to be clarified. The function of MC4R encoding melanocortin 4 receptor (MC4R) is somewhat better understood. alpha-, beta-, and gamma-MSH encoded by the POMC gene bind to MC4R, reduce food intake, and slow down fat accumulation. Expression of POMC that codes MSH is enhanced by leptin binding to the receptor (LepRb) in hypothalamic neurons. Mutations in human and animal MC4R, POMC, and LEP genes are known to be associated with obesity. More than 60 mutations in MC4R, more than 20 mutations in POMC and fewer LEP mutations have been reported. Nonsense mutations and reading frame shifts block gene expression and thereby disrupt protein synthesis. Missense mutations frequently affect protein folding in endoplasmic reticulum; unfolded or misfolded proteins remain in the cytoplasm and undergo degradation. Certain missence mutations do not interfere with gene expression and folding of proteins but impair their functioning at the periphery. P.S127L mutation in MC4R, p.E206X and p.F144L mutations in POMC as well as other mutations in homozygous and heterozygous forms account for disturbed energy balance in man. The LEP gene has been reported to contain G133fsX15, p.R105X, p.R1O5W, and p.S141C mutations. As a rule, they are associated with obesity and other pathological conditions only in homozygous forms.
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PMID:[Genetic variations in energy balance regulation]. 2134 4

Adipocyte-derived leptin is a hormone associated with the regulation of energy homeostasis, including glucose metabolism. Hyperleptinemia, induced by the consumption of energy-enriched diets, inhibits leptin transport across the blood-brain barrier, and thereby produces leptin insufficiency in the hypothalamus. As a result of sustained leptin insufficiency, the hypothalamic restraint on pancreatic insulin secretion is lost. Additionally, both glucose metabolism and energy expenditure are also diminished, and both type 1 and type 2 diabetes are induced. A replication-deficient recombinant adeno-associated virus vector engineered to encode the leptin gene (rAVV-LEP) has been used in models of diabetes as a novel therapeutic approach. After rAVV-LEP injection in ob/ob mice, hypothalamic leptin expression was increased, body weight was suppressed, and hyperinsulinemia was ameliorated. Additionally injection of rAVV-LEP into the hypothalamus suppressed the expression of orexigenic neuropeptide Y (NPY) and enhanced anorexigenic pro-opiomelanocortin (POMC) in the arcuate nucleus (ARC) in rats. It is proposed that central leptin gene therapy should be tested clinically to reduce the worldwide epidemic of obesity, diabetes, and shortened life span. In this article, the information has been assembled from published review articles on this topic.
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PMID:Long-term correction of type 1 and 2 diabetes by central leptin gene therapy independent of effects on appetite and energy expenditure. 2356 90

The autophagy-related proteins ATG12 and ATG5 form a covalent complex essential for autophagy. Here, we demonstrate that ATG12 has distinct functions from ATG5 in pro-opiomelanocortin (POMC)-expressing neurons. Upon high-fat diet (HFD) consumption, mice lacking Atg12 in POMC-positive neurons exhibit accelerated weight gain, adiposity, and glucose intolerance, which is associated with increased food intake, reduced ambulation, and decreased LEP/leptin sensitivity. Importantly, although genetic deletion of either Atg12 or Atg5 renders POMC neurons autophagy-deficient, mice lacking Atg5 in POMC neurons do not exhibit these phenotypes. Hence, we propose nonautophagic functions for ATG12 in POMC neurons that counteract excessive weight gain in response to HFD consumption.
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PMID:Loss of Atg12, but not Atg5, in pro-opiomelanocortin neurons exacerbates diet-induced obesity. 2558 51