Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The metabolic benefits of lixisenatide as an anti-diabetic agent are recognized but potential extra-pancreatic effects of this glucagon-like peptide-1 (GLP-1) mimetic in the brain are less well known. This study examines actions within the hippocampus following chronic 40-day peripheral administration of lixisenatide to high-fat fed mice with established obesity, insulin resistance and impaired cognition. Lixisenatide (50 nmol/kg bw, twice-daily) resulted in marked improvements in glycemic status, insulin secretion and insulin sensitivity. Examination of pancreatic tissue revealed decreased islet area, increased islet number, and increased insulin content, with no evidence of pancreatic inflammation. Lixisenatide improved recognition memory during a novel object recognition task and this was associated with up-regulation of hippocampal expression of neurotrophic tyrosine kinase receptor type 2 (NTRK2) and mammalian target of rapamycin (mTOR) genes involved in modulating synaptic plasticity and long-term potentiation. Lixisenatide also enhanced progenitor cell proliferation and increased the number of immature neurons in the hippocampal dentate gyrus. These data indicate that lixisenatide is not only a new efficacious drug for treatment of diabetes but it also exerts favorable neuroprotective effects, reversing memory impairment in obesity-diabetes. Further clinical studies are necessary to fully assess potential beneficial actions of lixisenatide in the hippocampus and cognition in man.
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PMID:Lixisenatide improves recognition memory and exerts neuroprotective actions in high-fat fed mice. 2519 84

Obesity and its comorbidities represent one of the major health problems worldwide. A positive energy balance due to inappropriate life-style changes plays a key role in the current obesity epidemic. The influence of genetic factors is also significant - several studies concluded that genes contribute to the development of obesity by 40-70%. Genetic variability predisposes an individual to tendency or resistance to increase body weight in obesogenic environment. Polygenic type of inheritance is responsible in most of obese individuals. However, an intensive research of the past 20 years has led to an identification of several genes causing monogenic forms of obesity. To date, several monogenic genes (leptin, leptin receptor, prohormon convertase 1, proopiomelanocortin, melanocortin 4 receptor, single-minded homolog 1, brain-derived neurotrophic factor, neurotrophic tyrosine kinase receptor type 2) that are either involved in the neuronal differentiation of the paraventricular nucleus or in the leptin-melanocortin pathway are known to cause obesity. Mutation carriers apart from severe early onset obesity manifest with additional phenotypic characteristics as adrenal insufficiency, impaired immunity and impaired fertility. This review provides an overview of molecular-genetic and clinical research in the field of monogenic obesities including therapeutical approaches.
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PMID:[Monogenic obesity - current status of molecular genetic research and clinical importance]. 2519 46