Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0028754 (obesity)
124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twelve morbidly obese patients and 17 patients treated for obesity by jejunoileal shunt operation were studied. A 50-g oral glucose load (OGTT) and an intravenous glucose infusion were carried out to study a) the relation between the plasma gastric inhibitory polypeptide (GIP) levels after oral glucose and the type of jejunoileal bypass performed and b) the importance of endogenous GIP as an incretin in man. The GIP release during OGTT and incretin effect were normal in the obese patients. After jejunoileal shunt, measuring 48 cm and with a ratio of 3:1 between the jejunal and ileal segments, the GIP release and the incretin effect were significantly reduced. Incremental increase in plasma GIP and OGTT was significantly correlated to the incretin effect in these patients. After jejunoileal shunt with the reverse ratio of proximal and distal intestine the incretin effect was significantly higher in spite of a comparable GIP release. Five patients after ileoascendostomia for familial hypercholesterolemia had significantly supernormal GIP release during OGTT but normal incretin effect. The findings indicate the insulinotropic effect of GIP and are in accordance with the concept that incretins other than GIP are released from the distal intestine.
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PMID:Gastric inhibitory polypeptide (GIP) release and incretin effect after oral glucose in obesity and after jejunoileal bypass. 700 14

Anatomopathological, biological and epidemiological studies suggest that raised cholesterol concentrations are associated with heightened risk for coronary heart disease. Preventive measures have been recommended by consensus conferences (prudent diet and cholesterol lowering drugs) for a "desirable" level of plasma total cholesterol, i.e.: 1.80 g/l before thirty years and 2 g after thirty years. The debates about the advantage of plasma cholesterol lowering have boosted many controversies after the completion of randomized primary and secondary prevention trials analyses. It was showed an increase in total mortality and a no reduction in fatal coronary events. A series of papers have tried to discourage physicians from identifying subjects with high risk. One has to continue to detect subjects with familial hypercholesterolemia and to treat them following the recommendations of consensus conferences. In the other cases, one has to attach value to HDL-cholesterol and plasma triglyceride levels, especially in patients with hyperinsulinemia, insulin resistance, hypertension and visceral obesity. As lipid oxidation products toxicity, protective diets, as the traditional mediterranean diet containing antioxidant components are important too. Relationships between lipoprotein status and hypercoagulability remains to be investigated to identify predictive factors better than cholesterol for atherothrombosis diseases in subjects at risk.
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PMID:[Cholesterol: consensus and controversies, what is the trend in 1993?]. 794 81

Total cholesterol levels, obesity index and blood pressure were measured in 6,278 school-age children living in Ibaraki Prefecture in 1991, and children with high risk for atherosclerosis were identified. The frequencies of the school-age children with hypercholesterolemia (total cholesterol > or = 200 mg/dl), obesity (obesity index > or = 40%) or hypertension were 7%, 5%, 1%, respectively. In half of the area where the children lived, lipid measurements were also obtained in the parents of hypercholesterolemic children. Twenty-nine out of ninety fathers (32%) and 22 out of 140 mothers (16%) were hypercholesterolemia (total cholesterol > or = 240 mg/dl). Among them five families of familial hypercholesterolemia were diagnosed. Seventy children with hypercholesterolemia and 81 obese children, who were screened and received health counseling, were re-examined after one year. The levels of LDL-cholesterol, triglyceride and atherogenic index were significantly decreased and HDL cholesterol level was significantly increased in the children with hypercholesterolemia. Obesity index, triglyceride level and atherogenic index were significantly decreased and HDL cholesterol level was significantly increased in the children with obesity. In addition, the frequencies of the children with dyslipidemia or liver dysfunction were significantly decreased in the obese children after one year. These data suggested that the screening system and the plans after the examinations described here were effective in reducing risk factors for atherosclerosis in children.
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PMID:[Cardiovascular risk factors among Japanese school-age children: a screening system for children with high risk for atherosclerosis in Ibaraki, Japan]. 811 Oct 84

We report the cloning of a 3656-bp cDNA encoding a putative human very low density lipoprotein (VLDL)/apolipoprotein E (ApoE) receptor. The gene encoding this protein was mapped to chromosome 9pter-p23. Northern analysis of human RNA identified cognate mRNAs of 6.0 and 3.8 kb with most abundant expression in heart and skeletal muscle, followed by kidney, placenta, pancreas, and brain. The pattern of expression generally paralleled that of lipoprotein lipase mRNA but differed from that of the low density lipoprotein (LDL) receptor and the low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor (LRP), which are members of the same gene family. VLDL/ApoE receptor message was not detected in liver, whereas mRNAs for both LDL receptor and LRP were found in hepatic tissue. In mouse 3T3-L1 cells, VLDL/ApoE receptor mRNA was induced during the transformation of the cells into adipocytes. Expression was also detected in human choriocarcinoma cells, suggesting that at least part of the expression observed in placenta may be in trophoblasts, cells which would be exposed to maternal blood. Expression in brain may be related to high levels of ApoE expression in that organ, an observation of potential relevance to the recently hypothesized role for ApoE in late onset Alzheimer disease. Our results suggest that the putative VLDL/ApoE receptor could play a role in the uptake of triglyceride-rich lipoprotein particles by specific organs including striated and cardiac muscle and adipose tissue and in the transport of maternal lipids across the placenta. The findings presented here, together with recent observations from other laboratories, bring up the possibility that a single gene, the VLDL/ApoE receptor, may play a role in the pathogenesis of certain forms of atherosclerosis, Alzheimer disease, and obesity.
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PMID:Cloning of a cDNA encoding a putative human very low density lipoprotein/apolipoprotein E receptor and assignment of the gene to chromosome 9pter-p23. 812 15

The principal goal of dietary treatment of heterozygous familial hypercholesterolemia (hFH) is the reduction of the plasma low density lipoprotein (LDL) cholesterol. This is best accomplished by enhancing the activity of LDL receptors and, at the same time, depressing liver synthesis of cholesterol. Both cholesterol and saturated fat down-regulate the LDL receptor and inhibit the removal of LDL from the plasma by the liver. Saturated fat down-regulates the LDL receptor, especially when cholesterol is concurrently present in the diet. The total amount of dietary fat is also important. The greater the flux of chylomicron remnants into the liver, the greater is the influx of cholesterol ester. In addition, factors that affect LDL synthesis could be important. These include excessive calories (obesity) that enhance very low density lipoprotein (VLDL) and, hence, LDL synthesis, and weight loss and omega-3 fatty acids, which depress synthesis of VLDL and LDL. The optimal diet for treatment of children and adults has the following characteristics: cholesterol (100 mg/day), total fat (20% of kcal, 6% saturated with the balance from omega-3 and omega-6 polyunsaturated and monounsaturated fat), carbohydrate (65% kcal, 67% from starch), and protein (15% kcal). This low-fat, high-carbohydrate diet can lower the plasma cholesterol 18-21%. A new concept, the Cholesterol-Saturated Fat Index, allows people to evaluate any foodstuff for its potential to elevate the plasma LDL cholesterol level. It is an antithrombotic diet, thrombosis being another major consideration in preventing coronary heart disease. Also, it contains significant amounts of antioxidants and fiber. Dietary therapy is the mainstay of treatment of hFH to which various drug therapies can be added.
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PMID:Importance of diet in the treatment of familial hypercholesterolemia. 821 96

Insulin resistance is found in association with obesity, non-insulin-dependent diabetes mellitus, and essential hypertension, which are all risk factors for atherosclerotic cardiovascular disease. Furthermore, hyperinsulinemia has been reported in familial combined hyperlipoproteinemia and endogenous hypertriglyceridemia. Finally, relatively high serum triglyceride and low high-density lipoprotein (HDL) cholesterol concentrations invariably accompany hyperinsulinemia. Whether insulin sensitivity is affected by the isolated presence of high levels of serum low-density lipoprotein (LDL) cholesterol has not been clearly established. We studied 13 subjects with heterozygous familial hypercholesterolemia (FHC) and 15 normocholesterolemic subjects selected to be free of any other known cause of insulin resistance. Thus FHC patients and controls had normal body weight and fat distribution, glucose tolerance, blood pressure, and serum triglyceride and HDL cholesterol concentrations, but were completely separated on plasma LDL cholesterol concentrations (6.05 +/- 0.38 v 3.27 +/- 0.15 mmol/L, P < .0001). Fasting plasma levels of glucose, insulin, free fatty acids (FFA), and potassium and fasting rates of net carbohydrate and lipid oxidation were superimposable in the two study groups. During a 2-hour euglycemic (approximately 5 mmol/L) hyperinsulinemic (approximately 340 pmol/L) clamp, whole-body glucose disposal rates averaged 30.4 +/- 2.3 and 31.1 +/- 3.0 mumol.kg-1 x min-1 in FHC and control subjects, respectively (P = 0.88). The ability of exogenous hyperinsulinemia to stimulate carbohydrate oxidation and energy expenditure and suppress lipid oxidation and plasma FFA and potassium levels was equivalent in FHC and control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Insulin sensitivity in familial hypercholesterolemia. 841 51

The review examines the evidence that the supply of cholesterol available for incorporation into nascent lipoprotein particles exerts a regulatory influence on apolipoprotein (apo) B secretion by the liver. Support for this hypothesis comes both from in vitro experiments and from recent observations in normal subjects and patients with dyslipidemia associated with familial hypercholesterolemia, obesity, noninsulin dependent diabetes mellitus, growth hormone deficiency and cholesteryl ester storage disease. The findings do not negate a role for triglyceride synthesis in determining apoB secretion in very low density lipoprotein, but the inhibitory effects on the latter process of pharmacological blockade of cholesterol synthesis or esterification suggest that it is conditional upon an adequate supply of cholesteryl ester.
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PMID:Role of cholesterol in regulating apolipoprotein B secretion by the liver. 872 9

Plasma lipoprotein cholesterol abnormalities, diabetes, hypertension and smoking have all been identified as independent predictors of cardiovascular events. Clustering of multiple risk factors suggests a common metabolic link among high blood pressure, insulin resistance, plasma lipoprotein abnormalities and obesity. New guidelines for the management of dyslipidemias target patients with established coronary artery disease (CAD), and high risk patients with multiple risk factors and severe genetic lipoprotein disorders, such as familial hypercholesterolemia. To determine the prevalence of lipoprotein, apolipoprotein and metabolic disorders in premature CAD, 243 men and 61 women with premature CAD (occurring before age 60 years) and 203 age- and sex-matched controls (152 men, 61 women) were studied. After correcting for beta-blocker use (40% of men and 54% of women), hypertension and diabetes were seen more frequently in CAD patients than in controls. In men and women, cholesterol, triglycerides, low density lipoprotein (LDL) cholesterol, apolipoprotein B and lipoprotein (a) were significantly higher, and high density lipoprotein (HDL) cholesterol was lower, in CAD patients than in controls. By stratifying patients according to LDL cholesterol: HDL cholesterol ratio (5 or less, or greater than 5) and by triglyceride levels (less than 2.3 mmol/L, or 2.3 mmol/L or greater), significantly more men and women with CAD were found to have an elevated LDL cholesterol:HDL cholesterol ratio and elevated triglycerides (13.8% versus 1.9%, men and women combined, CAD versus controls, P < 0.0001). A metabolic factor index was devised, assigning a score of 1 each for presence of hypertension, lipoprotein abnormalities, diabetes or fasting blood glucose above 7.0 mmol/L, and a body mass index of 27 or greater. The prevalence of a metabolic factor index of 3 or more was 29.2% in CAD men versus 6.7% in controls (P < 0.0001) and 38.3% in CAD women versus 11.7% in controls (P < 0.01). Familial hypercholesterolemia was seen in fewer than 5% of patients with premature CAD and type III dyslipoproteinemia in one of 343 CAD patients. The distribution of apolipoprotein E phenotypes was the same in CAD patients and controls. Multivariate analysis revealed that in men, HDL cholesterol, lipoprotein (a) levels and smoking were the best predictors of risk. In men, plasma levels of LDL cholesterol, triglycerides or body mass index did not enter the model at the P < 0.05 level. In women, low HDL cholesterol, lipoprotein (a), the presence of diabetes, smoking and apolipoprotein B levels were all predictors of risk (P < 0.05). However, the clustering of risk factors may be the best predictor of risk. In this selected population, HDL and lipoprotein (a) are the best metabolic markers of premature CAD; metabolic factor clustering is common in patients with premature CAD.
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PMID:Metabolic factors clustering, lipoprotein cholesterol, apolipoprotein B, lipoprotein (a) and apolipoprotein E phenotypes in premature coronary artery disease in French Canadians. 911 13

Hepatic cholesterol metabolism was studied in operative liver biopsies from 17 morbidly obese subjects and compared with that in samples from 15 nonobese controls. The aim was to understand the mechanisms causing the hypersecretion of cholesterol into bile. The content of cholesteryl esters was increased threefold in the liver of obese subjects compared with that of the controls (P < .0001). The activity and the messenger RNA (mRNA) level of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, the rate limiting enzyme for cholesterol synthesis, were higher in the obese subjects compared with the nonobese subjects (75% and 140%, respectively; P < .01). In the obese subjects, the activity and mRNA level of cholesterol 7alpha-hydroxylase, which regulates the catabolism of cholesterol to bile acids, were also increased by 140% (P < .05) and 180% (P = .06), respectively, as compared with the controls. There was a significant correlation between the activities and the mRNA levels of cholesterol 7alpha-hydroxylase among the obese subjects (r = +0.65, P < .01). The activities of acyl-coenzyme A:cholesterol acyltransferase (ACAT), which governs cholesteryl ester formation, in obese and nonobese patients were 12.5 +/- 1.7 and 8.1 +/- 1.2 pmol/min/mg protein, respectively (P < .05), and the low-density lipoprotein (LDL) receptor mRNA levels were 5.3 +/- 0.7 and 4.5 +/- 0.9 molecules of mRNA/microg of RNA, respectively. We conclude that the activities of three key enzymes in hepatic cholesterol metabolism were increased in morbidly obese subjects compared with nonobese controls, as were mRNA levels of HMG CoA reductase and cholesterol 7alpha-hydroxylase. The mRNA level of the LDL receptor in the obese subjects was not significantly changed. The hypersecretion of cholesterol occurring in obesity is neither due to a reduced conversion of cholesterol to bile acids nor to a decreased esterification of hepatic cholesterol but may be due to an increased synthesis of cholesterol.
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PMID:Hepatic cholesterol metabolism in human obesity. 918 66

The JCR:LA-cp rat is one of a number of strains incorporating the autosomal recessive cp gene that induces obesity. This strain is unique in the development of not only a profound insulin resistance, but an accompanying cardiovascular disease that correlates strongly with hyperinsulinemia. The hyperinsulinemia develops rapidly after 4 weeks of age, with an age at half-maximum of 5.5 weeks. This reflects postprandial plasma insulin levels that peak at 1000 mU/l in a standardized meal tolerance test. Defective acetylcholine-mediated vascular relaxation develops with a 1-week lag over the developing hyperinsulinemia. The frequency of staining for the vascular adhesion molecules, VCAM-1 and ICAM, does not show either age or genotype variation, although plasma levels do show an age variation. Treatment of the rats with the alpha-glucosidase inhibitor, miglitol (Bay m1099), obviates the exaggerated postprandial glucose and, especially, the insulin responses of the cp/cp rat. This causes an improvement in insulin sensitivity, prevention of the impaired vascular relaxation, and reduction in plasma levels of advanced glycated end-products. Arterial wall morphology, as visualized by both scanning and transmission electron microscopy, shows abnormal endothelium, adherent macrophages, and activated migrating smooth muscle cells in the intima. Oil-Red-O staining reveals lipid deposits in the intimal spaces, as confirmed by the presence of foam cells. The lesions resemble fatty streaks or modest atherosclerosis in man, rather than the extensive cholesterol-laden lesions seen in familial hypercholesterolemia or cholesterol-fed rabbit models. The lean rats of the strain show similar, but less marked, intimal abnormalities. The vasculopathy in this animal model appears to be precipitated by the developing hyperinsulinemia, but also requires an underlying abnormality of vascular smooth muscle and possibly also of the endothelium.
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PMID:Vasculopathy and insulin resistance in the JCR:LA-cp rat. 967 79


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