Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q8NEX9 (reductase)
 26,410 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We previously reported that dog diabetes results in hypercholesterolemia and the accumulation of a high-density lipoprotein (HDL) subclass, HDL1. Hypercholesterolemic diabetic rodents exhibit hyperphagia, intestinal hypertrophy, and increased intestinal cholesterol synthesis and absorption; intestinal 3-hydroxy-3-methylglutaryl (HMG) CoA reductase activity is increased, whereas hepatic activity is unchanged or reduced. To determine whether similar mechanisms operate in the hypercholesterolemic diabetic dog, we measured hepatic and intestinal cholesterologenesis. Streptozocin-alloxan-induced diabetic dogs allowed access to food ad libitum were hyperphagic and hypercholesterolemic (10.1 vs. 4.47 mM) but normotriglyceridemic. Plasma HDL1 concentrations were markedly increased. Differences in renal and hepatic function were not statistically significant, except serum alkaline phosphatase, which was elevated 4-fold (P = 0.0003). Urinary mevalonate, an index of whole-body cholesterol synthesis, was increased 6-fold. Intestinal and hepatic weights were both increased, and direct measurements showed crypt and villus thickening. The activity of HMG CoA reductase per gram organ weight was increased 1.7-fold in liver and 2.1-fold in intestine. Calculated whole-organ activity in intestine was nearly twice that in liver. These observations provide strong evidence that intestinal cholesterogenesis is involved in the pathogenesis of hypercholesterolemia in dog diabetes and support the conclusion that increased cholesterol synthesis plays a role in the hypercholesterolemia of diabetes.
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PMID:Intestinal and hepatic cholesterogenesis in hypercholesterolemic dyslipidemia of experimental diabetes in dogs. 175 3

This study was conducted to examine the effects of a combination of several dietary fibers (5% guar gum, 5% apple pectin, 15% wheat bran, 22% soybean fiber) and crude potato starch (23%) on plasma lipids and lipoproteins and on liver lipid concentration in rats fed a diet containing either 15% lard or 5% oil with or without dietary cholesterol/cholic acid. Male Wistar rats ate the test diets for 3 wk. The incorporation of fiber and crude potato starch into the diet resulted in a significant enlargement of the cecum; it also increased the concentration of volatile fatty acids and the pool of acetate, propionate and butyrate. Feeding this fermentable carbohydrate decreased plasma cholesterol and triglyceride levels in rats given a low fat diet and prevented the expected rise in plasma cholesterol and triglycerides in rats fed cholesterol/cholic acid or lard. Further studies of high density lipoprotein (HDL) composition, 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMG-CoA reductase) activity and 125I-labeled human low density lipoprotein (LDL) turnover were done in the group fed the low fat diet without added cholesterol/cholic acid. The study of the HDL fraction in rats fed a diet rich in fermentable carbohydrates demonstrated a decrease in the HDL1 subpopulation and in the proportion of apolipoprotein E. Plasma clearance of intravenously injected 125I-labeled LDL was faster in rats fed this diet than in rats fed the fiber-free diet. In the liver, cholesterol and triglyceride levels were depressed whereas the activity of HMG-CoA reductase was increased.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of diets rich in fermentable carbohydrates on plasma lipoprotein levels and on lipoprotein catabolism in rats. 216 42

The effect of different polysaccharides fermented in the large intestine and liable to lower plasma cholesterol was investigated in rats. Male rats were assigned to one of five treatment groups: control diet or a diet containing pectin, guar gum, gum arabic or beta-cyclodextrin. The four compounds were effectively fermented, yielding cecal short-chain fatty acids (SCFA) concentrations in the range of 130 to 170 mmol/L. Relative to controls, the cecal concentration of propionate was significantly higher in rats fed all fibers, especially those fed guar gum (+190%) or beta-cyclodextrin (+385%). All the fermented carbohydrates elicited a significant cholesterol-lowering effect, which was most potent in rats fed guar gum or beta-cyclodextrin, the two fibers that also significantly depressed plasma triglycerides. These two carbohydrates significantly lowered LDL and HDL1 cholesterol, triglyceride-rich lipoprotein triglycerides and apolipoprotein E levels. Apolipoprotein B was lowered only by beta-cyclodextrin. The microsomal activities of hydroxymethylglutaryl (HMG) CoA reductase and of cholesterol 7 alpha-hydroxylase were markedly elevated in rats fed guar gum or beta-cyclodextrin and, to a lesser extent, in those fed pectin compared with controls. Increased bile acid excretion seems to be essential in the cholesterol-lowering effect of soluble fibers and related compounds. This effect is connected to induction of HMG CoA reductase and lowering concentrations of apolipoprotein E-containing particles.
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PMID:Fermentable polysaccharides that enhance fecal bile acid excretion lower plasma cholesterol and apolipoprotein E-rich HDL in rats. 796 2