Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242339 (dyslipidemia)
 13,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuropeptide Y (NPY) appears to play a critical role in the integration of appetite and energy expenditure through NPY Y1 and Y5 receptor subtypes. Moreover, the NPY Y1 receptor is highly expressed on human adipocytes, where it inhibits lipolysis. The genes encoding these receptors are transcribed co-ordinately in opposite directions from a common promoter in a region of chromosome 4 that has been previously linked to triglyceride and small low-density lipoprotein (LDL) particle concentration. Therefore, the purpose of this investigation was to examine the relationship between polymorphisms in the genes encoding NPY Y1 and Y5 and the development of obesity and dyslipidemia. We screened the promoter and coding regions and identified four polymorphic variants. One of these, a cytosine to thymine (C-->T) substitution in the untranslated region between the genes for NPY Y1 and Y5 (allele frequency 0.11), was significantly associated with both lower fasting triglyceride level (152 vs 125 mg/dl), and higher high-density lipoprotein (HDL) concentrations (49 vs 45 mg/dl) (p < 0.01) in 306 obese subjects. Given the stimulatory effect of NPY on adipocyte lipoprotein lipase (LPL) activity, and the lack of association of other polymorphisms with serum lipid levels, we hypothesize that this is a gain-in-function polymorphism.
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PMID:Novel neuropeptide Y1 and Y5 receptor gene variants: associations with serum triglyceride and high-density lipoprotein cholesterol levels. 1222 Apr 33

We examined the genetic association of neuropeptide Y receptor Y5 (NPY5R) single nucleotide polymorphisms (SNPs) with measures of the insulin resistance (metabolic) syndrome. We genotyped 10 NPY5R SNPs in 439 Mexican American individuals (age=43.3+/-17.3 years and BMI=30.0+/-6.7 kg/m2) distributed across 27 pedigrees from the San Antonio Family Diabetes Study and performed association analyses using the measured genotype approach as implemented in Sequential Oligogenic Linkage Analysis Routines (SOLAR). Minor alleles for five (rs11100493, rs12501691, P1, rs11100494, rs12512687) of the NPY5R SNPs were found to be significantly (p<0.05) associated with fasting plasma triglyceride concentrations and decreased high-density lipoprotein concentrations. In addition, the minor allele for SNP P2 was significantly associated (p=0.031) with a decreased homeostasis model assessment of beta-cell function (HOMA-%beta). Linkage disequilibrium between SNP pairs indicated one haplotype block of five SNPs (rs11100493, rs12501691, P1, rs11100494, rs12512687) that were highly correlated (r2>0.98). These preliminary results provide evidence for association of SNPs in the NPY5R gene with dyslipidemia (elevated triglyceride concentrations and reduced high-density lipoprotein levels) in our Mexican American population.
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PMID:Association of neuropeptide Y receptor Y5 polymorphisms with dyslipidemia in Mexican Americans. 1742 13

Biochemical tests such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are useful for diagnosing patients with liver disease. In this study, we tested the association between copy number variation and the hepatic biomarkers AST and ALT based on 8,842 samples from population-based cohorts in Korea. We used Affymetrix Genome-Wide Human 5.0 arrays and identified 10,534 CNVs using HelixTree software. Of the CNVs tested using univariate linear regression, 100 CNVs were significant for AST and 16 were significant for ALT (P < 0.05). We identified 39 genes located within the CNV regions. DKK1 and HS3ST3B1 were shown to play roles in heparan sulfate biosynthesis and the Wnt signaling pathway, respectively. NAF1 and NPY1R were associated with glycoprotein processes and neuropeptide Y receptor activity based on GO categories. PTER, SOX14 and TM7SF4 were expressed in liver. DPYS and CTSC were found to be associated with dihydropyrimidinuria and Papillon-Lefevre syndrome phenotypes using OMIM. NPY5R was found to be associated with dyslipidemia using the Genetic Association Database.
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PMID:Analysis of copy number variation in 8,842 Korean individuals reveals 39 genes associated with hepatic biomarkers AST and ALT. 2079 17

Elevated plasma triglyceride (TG) levels contribute to an atherogenic dyslipidemia that is associated with obesity, diabetes, and metabolic syndrome. Numerous models of obesity are characterized by increased central nervous system (CNS) neuropeptide Y (NPY) tone that contributes to excess food intake and obesity. Previously, we demonstrated that intracerebroventricular (icv) administration of NPY in lean fasted rats also elevates hepatic production of very low-density lipoprotein (VLDL)-TG. Thus, we hypothesize that elevated CNS NPY action contributes to not only the pathogenesis of obesity but also dyslipidemia. Here, we sought to determine whether the effects of NPY on feeding and/or obesity are dissociable from effects on hepatic VLDL-TG secretion. Pair-fed, icv NPY-treated, chow-fed Long-Evans rats develop hypertriglyceridemia in the absence of increased food intake and body fat accumulation compared with vehicle-treated controls. We then modulated CNS NPY signaling by icv injection of selective NPY receptor agonists and found that Y1, Y2, Y4, and Y5 receptor agonists all induced hyperphagia in lean, ad libitum chow-fed Long-Evans rats, with the Y2 receptor agonist having the most pronounced effect. Next, we found that at equipotent doses for food intake NPY Y1 receptor agonist had the most robust effect on VLDL-TG secretion, a Y2 receptor agonist had a modest effect, and no effect was observed for Y4 and Y5 receptor agonists. These findings, using selective agonists, suggest the possibility that the effect of CNS NPY signaling on hepatic VLDL-TG secretion may be relatively dissociable from effects on feeding behavior via the Y1 receptor.
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PMID:Central nervous system neuropeptide Y signaling via the Y1 receptor partially dissociates feeding behavior from lipoprotein metabolism in lean rats. 2307 43

Olanzapine-induced weight gain is associated with atherosclerosis, hypertension, dyslipidemia, and diabetes. We synthesized a novel antipsychotic drug (PGW5) possessing an olanzapine moiety linked to sarcosine, a glycine transporter 1 inhibitor. In this study, we compared the metabolic effects of PGW5 and olanzapine in a female rat model of weight gain. Female rats were treated daily with oral olanzapine (4 mg/kg), PGW5 (25 mg/kg), or vehicle for 16 days. Behavioral tests were conducted on days 12-14. Biochemical analyses were performed at the end of the treatment. A significant increase in body weight was observed in the olanzapine-treated group, while the PGW5 group did not differ from the controls. The open field test showed hypo-locomotion in the olanzapine-treated animals as compared to PGW5 and control groups. A significant increase in hypothalamic protein expression of the neuropeptide Y5 receptor and a decrease in pro-opiomelanocortin messenger ribonucleic acid (mRNA) levels were detected following PGW5 treatment, but not after olanzapine administration. PGW5 appears to possess minor metabolic effects compared with the parent compound olanzapine. The differential modulation of brain peptides associated with appetite regulation is possibly involved in the attenuation of metabolic effects by PGW5.
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PMID:Attenuated Weight Gain with the Novel Analog of Olanzapine Linked to Sarcosinyl Moiety (PGW5) Compared to Olanzapine. 2657 34