Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020505 (hyperphagia)
 6,116 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Postprandial hyperlipidemia (PH) is recognized as a significant risk factor for cardiovascular disease. The present study, involving rats with streptozotocin (STZ)-induced diabetes, was performed to establish a PH model and to examine the relation between small intestinal acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity and serum lipid levels in the postprandial state. The small intestinal ACAT activities in normal rats during the experimental period were 4 to 5 pmol/mg protein per minute. In contrast, in the diabetic rats, the ACAT activities were 2 to 3 times higher than activities seen in normal rats from 7 to 21 days after the STZ injection in the absence of a high fat diet and hyperplasia in the gut. In an oral fat-loading test that used diabetic rats that had been injected with STZ (60 mg/kg) intravenously 14 days previously, the postloading changes in the serum concentrations of total cholesterol (TC) and triglyceride (TG) were significantly greater in the diabetic rats than in normal rats. Single oral administration of (1s,2s)-2-[3-(2,2-dimethylpropyl)-3-nonylureido]cyclohexane- 1-yl 3-[(4R)-N-(2,2,5,5-tetramethyl-1, 3-dioxane-4-carbonyl)amino]propionate (F-1394, 3 to 30 mg/kg), a potent ACAT inhibitor, suppressed the post-fat-loading elevation of serum TC levels in the diabetic rats in a dose-dependent manner without affecting serum glucose levels. Furthermore, the small intestinal ACAT activity, serum TG levels, and lymphatic absorption of TC and TG in the rats that were administered F-1394 (30 mg/kg) were reduced by approximately 90%, 70%, 30%, and 15%, respectively. This is the first evidence that elevated ACAT activity in the gut, unlike hyperplasia and hyperphagia, induces PH in rats. Our results strongly suggest that F-1394 may be a potential treatment for PH in humans.
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PMID:Postprandial hyperlipidemia in streptozotocin-induced diabetic rats is due to abnormal increase in intestinal acyl coenzyme A:cholesterol acyltransferase activity. 1063 14

It has previously been shown that the intravenous administration of the 5-HT(1A) receptor agonist, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), increases food intake in satiated pigs and decreases food intake in fasted pigs. The present experiments were conducted to investigate the effects of central administration of the 5-HT(1A) receptor antagonist, N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]-N-2-pyridinyl-cyclohexane carbox-amide maleate (WAY 100635), on the stimulant and depressant effects of 8-OH-DPAT on operant food intake in satiated and hungry pigs. In Experiment 1, 8-OH-DPAT (25 microg/kg) produced an increase in operant feeding during the first 30 min following intravenous administration to satiated pigs. The 8-OH-DPAT-induced hyperphagia was completely abolished by pretreatment with WAY 100635 (0.3 mg) administered by intracerebroventricular injection. In Experiment 2, 8-OH-DPAT (25 microg/kg) administered intravenously 15 min prior to the onset of feeding in pigs that had been fasted for 22.5 h produced a decrease in operant food intake, which was most apparent during the first 30 min of the feeding period. The hypophagic effect was completely abolished by pretreatment with WAY 100635 (0.3 mg icv) administered 30 min before the start of the feeding period. In both experiments, WAY 100635 (0.3 mg icv) did not have any significant effects on feeding. The results of the present study extend previous results in the pig and show that both the hyperphagic and the hypophagic effects of 8-OH-DPAT in satiated and fasted pigs, respectively, are mediated by central 5-HT(1A) receptors.
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PMID:The differential effects of intravenously administered 8-OH-DPAT on operant food intake in satiated and food-deprived pigs are mediated by central 5-HT(1A) receptors. 1139 15