Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.1.21 (CPT)
 4,580 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tub is a member of a small gene family, the tubby-like proteins (TULPs), with predominant expression in neurons. Mice carrying a mutation in Tub develop retinal and cochlear degeneration as well as late-onset obesity with insulin resistance. During behavioral and metabolic testing, we found that homozygous C57BL/6J-Tub(tub) mice have a lower respiratory quotient than C57BL/6J controls before the onset of obesity, indicating that tubby homozygotes fail to activate carbohydrate metabolism and instead rely on fat metabolism for energy needs. In concordance with this, tubby mice show higher excretion of ketone bodies and accumulation of glycogen in the liver. Quantitation of liver mRNA levels shows that, during the transition from light to dark period, tubby mice fail to induce glucose-6-phosphate dehydrogenase (G6pdh), the rate-limiting enzyme in the pentose phosphate pathway that normally supplies NADPH for de novo fatty acid synthesis and glutathione reduction. Reduced G6PDH protein levels and enzymatic activity in tubby mice lead accordingly to lower levels of NADPH and reduced glutathione (GSH), respectively. mRNA levels for the lipolytic enzymes acetyl-CoA synthetase and carnitine palmitoyltransferase are increased during the dark cycle and decreased during the light period, and several citric acid cycle genes are dysregulated in tubby mice. Examination of hypothalamic gene expression showed high levels of preproorexin mRNA leading to accumulation of orexin peptide in the lateral hypothalamus. We hypothesize that abnormal hypothalamic orexin expression leads to changes in liver carbohydrate metabolism and may contribute to the moderate obesity observed in tubby mice.
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PMID:Defective carbohydrate metabolism in mice homozygous for the tubby mutation. 1684 32

The objective of the study was to investigate the regulatory actions of unacylated ghrelin (UAG) on glucose-sensitive (GS) neurons and glycolipid metabolism in the lateral hypothalamus area (LHA) and its involvement with orexin-A-immunopositive neurons. The effects of UAG administered into the LHA on GS neurons discharges and glycolipid metabolism were detected by single neuron discharge recording, biochemical index analysis and quantitative real-time PCR; the level of c-fos protein in orexin-A-immunopositive neurons was observed using immunofluorescence staining. UAG microinjected into the LHA activated glucose-inhibited neurons, which were partially blocked by pre-administration of anti-orexin-A antibody in the LHA. Furthermore, UAG microinjected into the LHA significantly reduced serum triglycerides (TG), total cholesterol, low-density lipoprotein cholesterol, blood glucose, insulin and hepatic TG levels, while elevated serum high-density lipoprotein cholesterol levels. UAG elevated the mRNA expression of carnitine palmitoyltransferase-1 and reduced the mRNA expression of acetyl-CoA carboxylase-1 in the liver. The above-mentioned effects of UAG were partially blocked by pre-administration of anti-orexin-A antibody. The expressions of orexin-A and c-fos were observed in the LHA. After UAG injection into the LHA, some neurons showed double labeling, and the percentage of double-labeled orexin-A/c-fos neurons in orexin-A-immunopositive neurons increased significantly. UAG in the LHA regulates glycolipid metabolism by activating orexin-A-immunopositive neurons in the LHA.
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PMID:Unacylated Ghrelin Regulates Glucose-Sensitive Neurons Activity and Glycolipid Metabolism via Orexin-A Neurons in the Lateral Hypothalamic Area. 3273 Dec 63