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)

Weight gain in ovariectomized Syrian hamsters occurs without increased food intake, which suggests that metabolic efficiency may be enhanced through a reduction in energy expenditure. We examined the effect of ovariectomy on metabolic activity in brown adipose tissue and liver. Four groups of hamsters (n = 13, each) were killed 0, 2, 4, or 16 weeks following ovariectomy. Ovariectomized hamsters rapidly gained weight without overeating. Body weights stabilized after 8 weeks and remained 12-17% above sham-operated control weights for the duration of the experiment. Weight gain in the hamsters ovariectomized for 16 weeks was characterized by significant increases in retroperitoneal white adipose tissue weight and carcass lipid content. Similar trends were seen in 2-week and 4-week ovariectomized animals. There were no differences in interscapular brown adipose tissue weight, protein content, DNA content, or norepinephrine (NE) content among sham-operated and 2-, 4-, or 16-week ovariectomized hamsters, indicating that ovariectomy had no effect on brown adipose tissue growth. Similarly, there was no difference in either sympathetic nervous system activity (estimated by the rate of NE turnover) or mitochondrial GDP binding among the four groups of hamsters. In contrast, hepatic cytochrome P-450 activity was significantly reduced 2, 4, and 16 weeks after ovariectomy. These results suggest that reduced thermogenic activity in liver, but not in brown adipose tissue, could contribute to the weight gain in Syrian hamsters after ovariectomy.
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PMID:Effects of ovariectomy on thermogenesis in brown adipose tissue and liver in Syrian hamsters. 194 29

Decreased drug metabolism and hepatic cytochrome P-450 levels have been shown previously to occur in rats receiving total parenteral nutrition (TPN) compared to animals receiving the same hyperalimentation solution enterally (TEN). In the present studies, animals received a 7-day infusion of a 25% glucose-2.75% crystalline amino acid solution via a catheter in the jugular vein or stomach; hepatic microsomal levels of four major constitutive cytochromes P-450 were determined subsequently by immunoquantitation and correlated with metabolism of selected substrates biotransformed by these enzymes. TPN resulted in a marked decrease in apoprotein of two constitutive cytochromes P-450, P-450UT-A and P-450PCN-E, compared to TEN experiments (for P-450UT-A, 11.0 +/- 1.8 vs 44.7 +/- 6.5% of total cytochrome P-450 measured by CO-difference spectra, P greater than 0.001; for P-450PCN-E, 15.4 +/- 4.4 vs 30.2 +/- 7.6%, P less than 0.01), but apoprotein levels of two other constitutive cytochromes P-450, P-450PB-C and P-450UT-F, showed relatively little change. Concordant reductions in metabolism of benzphetamine, ethylmorphine and erythromycin were seen in TPN animals. While the mechanisms responsible for these selective changes in the synthesis and function of individual cytochromes P-450 remain to be elucidated, altered gene transcription due to differences in portal blood composition elicited by intravenous versus enteral feeding is a possible hypothesis. These studies also provide information which should be valuable in designing studies to probe further the clinical question of whether TPN induces significant alterations in human drug metabolism.
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PMID:Selective alteration of constitutive hepatic cytochrome P-450 enzymes in the rat during parenteral hyperalimentation. 251 Jul 31

1. In the absence of intraluminal inducers, low "basal" levels of cytochrome P-450 and its dependent MFO activities are detected in the rat intestinal mucosa, and may be regulated by endogenous hormones. 2. Rats were nutritionally maintained by either short term (48 hr) intravenous glucose infusion or chronic (8 days) intravenous hyperalimentation, and were treated with various doses of pentagastrin in the infusate. 3. Regardless of the dose (6-90 micrograms/kg/hr) or duration of infusion (2-8 days), pentagastrin had no effect on small intestinal cytochrome P-450, its dependent MFO activity, or the activity of delta-aminolevulinic acid synthetase. 4. The intestinal trophic peptide hormone, gastrin, apparently does not regulate the cytochrome P-450-dependent MFO system of the small intestine.
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PMID:Role of gastrin/pentagastrin in regulation of intestinal cytochrome P-450. 290 72

Whereas patients receiving parenteral hyperalimentation frequently have abnormalities in serum liver enzymes, the influence of i.v. administration of hypertonic glucose-protein solutions on hepatic function has received little attention. Recent data from this laboratory indicated that in vivo clearance of pentobarbital was significantly decreased in rats receiving total parenteral hyperalimentation (TPN) vs. animals receiving the same hyperalimentation solution enterally (total enteral hyperalimentation; TEN). To determine the cause of this decreased clearance, we have analyzed mixed-function oxidase activity in hepatic microsomes prepared from livers of rats receiving 7 day continuous i.v. or i.g. infusions of hypertonic glucose (25%) combined with fibrin hydrolysate or crystalline amino acids. Hepatic microsomal cytochrome P-450 and capacity for demethylation of meperidine and hydroxylation of pentobarbital were significantly reduced in TPN animals as compared to TEN and ad libitum chow-fed control rats. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of microsomal protein revealed increased staining of a 46,500 molecular weight band and decreased intensity of a 52,700 molecular weight band in TPN experiments as compared to TEN studies. Increasing amino acid concentration in infusions to 4.25% from the standard 2.75% resulted in marked reductions in hepatic microsomal drug metabolism in enterally hyperalimented animals. These studies show that the route of alimentation delivery has an important influence on hepatic drug metabolic function in rats and suggest that quantitative and/or qualitative differences in hepatic delivery of protein may be responsible for the quantitative and qualitative differences in hepatic microsomal mixed-function oxidases observed between TPN and TEN animals. If similar changes occur in humans receiving TPN, major alterations in drug regimens may be required.
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PMID:Effects of parenteral and enteral hyperalimentation on hepatic drug metabolism in the rat. 642 94