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)

To study the in vivo role of apolipoprotein (apo) C1 in lipoprotein metabolism, we have generated transgenic mice expressing the human apo C1 gene. Apo C1 is a small 6.6 kDa protein that is primarily synthesized by the liver and is present on chylomicrons, very low density lipoproteins (VLDL) and high density lipoproteins (HDL). In recent years, studies by our group have shown that apo C1 transgenic mice develop hyperlipidemia due to an accumulation of VLDL-sized lipoprotein particles. The underlying metabolic defect in apo C1 transgenic mice is an impaired uptake of VLDL particles by the liver. Although a role for apo C1 in human disease remains to be established, data presented in the current paper show that apo C1 transgenic mice are an instructive model of hyperlipidemia to (i) elucidate possible mechanisms underlying this disorder and (ii) test the activity and mode of action of hypolipidemic drugs.
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PMID:Effects of fenofibrate on hyperlipidemia and postprandial triglyceride metabolism in human apolipoprotein C1 transgenic mice. 988 47

The lipid microenvironment of receptors can influence their conformation, function, and regulation. Cholecystokinin (CCK)-stimulated signaling is abnormal in some forms of hyperlipidemia, suggesting the possibility of unique sensitivity to its lipid environment. Here we examined the influence of cholesterol and sphingolipids on CCK receptors in model Chinese hamster ovary cell systems having lipid levels modified. Cholesterol was modulated chemically or metabolically, and sphingolipids were modulated using a temperature-sensitive cell line (SPB-1). Receptor conformation was probed with a fluorescent full agonist ligand, Alexa 488-conjugated Gly-[Nle(28,31)]CCK-(26-33), shown previously to decrease in anisotropy and lifetime when occupying a receptor in the active conformation (Harikumar, K. G., Pinon, D. L., Wessels, W. S., Prendergast, F. G., and Miller, L. J. (2002) J. Biol. Chem. 277, 18552-18560). Anisotropy and lifetime of this probe were increased and prolonged with cholesterol enrichment, and decreased and shortened with depletion of cholesterol or sphingolipids. The increase in these parameters with cholesterol enrichment may reflect change in CCK receptor conformation toward its inactive, uncoupled state. Indeed, cholesterol enrichment resulted in nonproductive agonist ligand binding, with affinity of binding higher than normal and calcium signaling in response to this reduced. In cholesterol- and sphingolipid-depleted states, the receptor moved into conformations that were less than optimal. With cholesterol depletion, both ligand binding and signaling were decreased, yet internalization and trafficking were unperturbed. With sphingolipid depletion, ligand binding and signaling were normal, but internalization and trafficking were markedly inhibited. Of note, normal transferrin receptor trafficking through the same clathrin-dependent pathway was maintained under these conditions. Thus, lipid microenvironment of the CCK receptor is particularly important, with different lipids having distinct effects.
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PMID:Differential effects of modification of membrane cholesterol and sphingolipids on the conformation, function, and trafficking of the G protein-coupled cholecystokinin receptor. 1553 36

It has been reported that subjects with prehypertension (pre-HT) (systolic blood pressure [SBP] 120-139 mmHg and/or diastolic blood pressure [DBP] 80-89 mmHg) have an increased risk of cardiovascular disease (CVD). We evaluated the prevalence and determinants of pre-HT in a Japanese general population. We enrolled 4,706 males and 7,342 females aged 18 to 90 years whose BPs were measured at baseline. The subjects' BPs were classified as follows: normotension (NT: SPB/DBP < 120/80 mmHg), pre-HT (120/80-139/89 mmHg), and hypertension (HT: > or = 140/90 mmHg or treated hypertension). The prevalence of pre-HT was 34.8% (males), and 31.8% (females). Body mass index (BMI) of more than 23.0 kg/m2 was the strongest determinant of pre-HT (Males--BMI: 23.0-24.9 kg/m2, odds ratio [OR] = 1.47, 95% confidence interval [CI] = 1.21-1.79; BMI: 25.0-26.9 kg/m2, OR = 2.20, 95% CI =1.68-2.87; BMI: 27.0-29.9 kg/m2, OR = 2.75, 95% CI = 1.80-4.19; BMI: > or = 30.0 kg/m2, OR = 3.39, 95% CI = 1.21-9.46. Females--BMI: 23.0-24.9 kg/m2, OR = 1.67, 95% CI = 1.42-1.95; BMI: 25.0-26.9 kg/m2, OR = 1.79, 95% CI = 1.46-2.19; BMI: 27.0-29.9 kg/m2, OR = 3.65, 95% CI = 2.73-4.89; BMI: > or = 30.0 kg/m2, OR = 4.23, 95% CI = 2.33-7.70). The other determinants of pre-HT were hyperlipidemia (Males: OR = 1.25; Females: OR = 1.43), and aging (by 10 years; Males: OR = 1.12; Females: OR = 1.48). Determinants of pre-HT in females were impaired glucose tolerance (OR = 1.41, 95% CI = 1.03-1.94), diabetes (OR = 2.01, 95% CI = 1.16-3.47) and a family history of HT in both parents (OR = 1.90, 95% CI = 1.38-2.62), whereas in males the only other predictor was alcohol drinking (OR = 1.45, 95% CI = 1.23-1.70). In conclusion, even subjects with a mild increase of BMI (23.0-24.9 kg/m2) had an increased risk of pre-HT in a Japanese population, and the level of BMI associated with pre-HT was lower than that in Western countries. Additionally, there were gender differences in the determinants of pre-HT.
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PMID:Prevalence and determinants of prehypertension in a Japanese general population: the Jichi Medical School Cohort Study. 1895 94