Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adverse nutritional effects on developing foetal hypothalamic appetitive pathways may contribute to programmed hyperphagia and obesity in intra-uterine growth-restricted, low birth weight offspring. In the present study, for the first time, hypothalamic gene expression for primary orexigenic and anorexigenic genes was examined in late gestation ovine foetuses (130 days; term=145 days) whose mothers were undernourished (UN) or well-nourished (C) throughout pregnancy, or transferred from UN to C on day 90 (UN-C). Pregnancies resulted from singleton embryo transfer into adolescent growing ewes. Body weight, carcass fat content and perirenal adipose tissue (PAT) mass were all lower for UN (n=9) than C (n=7) and intermediate for UN-C foetuses (n=6), with no effect of sex. PAT leptin gene expression (by the reverse transcriptase-polymerase chain reaction) was lower in UN than C and UN-C groups, and lower in males than females. Gene expression (by in situ hybridisation with radiolabelled riboprobes) in the arcuate nucleus was greater in UN than C foetuses for neuropeptide Y (NPY), agouti-related peptide (AGRP) and leptin receptor (OBRb) but not different for pro-opiomelanocortin and cocaine- and amphetamine-regulated transcript. Gene expression in UN-C foetuses was intermediate for NPY and AGRP and not different from C foetuses for OBRb. Gene expression for NPY, AGRP and OBRb correlated negatively with foetal carcass fat content and with PAT leptin gene expression across all groups. Males had greater mRNA expression for AGRP than females, with NPY and OBRb showing similar trends. Therefore, maternal undernutrition throughout pregnancy increased orexigenic gene expression in the late gestation foetal hypothalamus, and expression levels were largely normalised by improved maternal nutrition in the last third of pregnancy. These findings may have implications for avoiding or correcting prenatal programming of postnatal hyperphagia and obesity.
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PMID:Orexigenic Gene Expression in Late Gestation Ovine Foetal Hypothalamus is Sensitive to Maternal Undernutrition and Realimentation. 2621 39

Pro-opiomelanocortin (POMC) neurones within the hypothalamic arcuate nucleus are vital anorexigenic neurones. Both the insulin receptor and leptin receptor are coupled to activation of phosphatidylinositide-3 kinase (PI3K) to regulate multiple functions that increase POMC neuronal excitability. Using whole-cell recording in several mammalian species, we have found that both insulin and leptin depolarised POMC neurones via activation of transient receptor potential (TRPC)5 channels. TRPC5 channels have been rigorously characterised as the downstream effector based on their biophysical properties, pharmacological profile, and localisation by immunocytochemistry and single-cell reverse transcriptase-polymerase chain reaction. By contrast, insulin and leptin hyperpolarise and inhibit neuropeptide Y/agouti-related peptide neurones via activation of KATP channels. As proof of principle, insulin given i.c.v. robustly inhibits food intake and increases O2 utilisation, CO2 production and metabolic heat production. Therefore, these findings indicate that the depolarisation/excitation of POMC neurones by insulin and leptin is preserved across mammalian species and the activation of TRPC5 channels is likely a major mechanism by which insulin and leptin regulate energy homeostasis in mammals.
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PMID:Insulin and leptin excite anorexigenic pro-opiomelanocortin neurones via activation of TRPC5 channels. 2867 83


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