Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activity and submicrosomal distribution of alpha-glycerophosphate acyltransferase (GPAT) were studied in rats fed ethanol for 6 wk. GPAT activity was also measured in rats after 10 days of alcohol feeding, 22 days of phenobarbital administration, or 24 days on a high fat (71% of total calories) diet. After 6 wk of ethanol feeding, GPAT activity was increased 73% when expressed per milligram of protein and 133% when expressed per 100 g of body weight (P < 0.005). GPAT activity was more abundant in the smooth than in the rough microsomes of both control and ethanol-fed rats when expressed per milligram of microsomal protein and when expressed per gram of liver; the smooth microsomes accounted for most of the increased GPAT activity after ethanol. 10 days of ethanol feeding or 22 days of phenobarbital administration did not increase GPAT activity. Feeding a high fat diet for 24 days increased GPAT activity per milligram of protein to an extent similar to that observed after chronic ethanol administration. When expressed per 100 g of body weight, however, the increase was much greater after ethanol. The significance of these findings in vivo has not been elucidated. Increased GPAT activity might contribute to the persistence of alcoholic fatty liver and the development of hyperlipemia.
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PMID:Effect of chronic ethanol feeding on hepatic microsomal glycerophosphate acyltransferase activity. 970 79

The mammalian target of rapamycin (mTOR) is a conserved serine-threonine kinase that regulates cell growth and metabolism in response to nutrient signals. However, the specific involvement of mTOR in regulation of energy metabolism is poorly understood. To determine if signaling via mTOR might be directly involved in regulation of fatty acid metabolism in hepatocytes, we performed studies with rapamycin, a specific inhibitor of mTOR. Rapamycin-mediated inhibition of mTOR (18-48 hours) increased oxidation of exogenous fatty acids (46%-100%, respectively). In addition, esterification of exogenous fatty acids and de novo lipid synthesis were reduced (40%-60%, respectively). Consistent with inhibition of lipogenic pathways, rapamycin decreased expression of genes encoding acetyl-coenzyme A carboxylase I and mitochondrial glycerol phosphate acyltransferase. Non-insulin-dependent glucose transport and glycogen synthesis were decreased by 20% to 30%, whereas glucose utilization was unaffected by rapamycin. The data suggest that the hyperlipidemia observed with the drug in vivo is likely not the result of enhanced hepatic synthesis, but rather of delayed peripheral clearance. However, these results are consistent with the idea that mTOR may play a significant role, not only in "energy sensing," but also in regulation of energy production through profound effects on hepatic fatty acid metabolism.
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PMID:The mammalian target of rapamycin regulates lipid metabolism in primary cultures of rat hepatocytes. 1795 Jan