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)

Obesity is a growing health problem in developed nations and in countries that are in the process of westernization like India. Obesity is linked with several health disorders such as hypertension and cardiovascular diseases, Type 2 diabetes, dyslipidemia and certain cancers. Currently, obesity-related malignancies, e.g., cancers of the breast, prostate and colon are the leading cancers in the industrialized societies. An increased amount of fat or adipose tissue in an overweight or obese person probably influences the development of cancer by releasing several hormone-like factors or adipokines. The majority of adipokines are pro-inflammatory, which promote pathological conditions like insulin resistance and cancer. On the other hand, many recent studies have shown that adiponectin, an anti-inflammatory adipokine, has anti-cancer and insulin-sensitizing effects. Adiponectin exerts its physiological functions chiefly by activation of AMP kinase via adiponectin receptors. Interestingly, several fruits and vegetables may contain adiponectin-like molecules or may increase the biosynthesis of adiponectin in our body. Studies on adiponectin analogues or adiponectin receptor agonists are a promising area of cancer chemoprevention research. In general, fruits and vegetables contain various dietary substances such as vitamins, minerals (like calcium and selenium), fiber and phytochemicals or phenolic compounds (like flavonoids and vanilloids), which may act as anti-cancer agents. Similarly, several dietary constituents including phytochemicals may have anti-obesity effects. Consumption of such dietary compounds along with caloric restriction and physical activity may be helpful in preventing obesity-related cancers. For this review article, we searched PubMed primarily to get the relevant literature.
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PMID:Dietary factors and cancer chemoprevention: an overview of obesity-related malignancies. 1924 81

Fenofibrate, widely used for the treatment of dyslipidemia, activates the nuclear receptor, peroxisome proliferator-activated receptor alpha. However, liver toxicity, including liver cancer, occurs in rodents treated with fibrate drugs. Marked species differences occur in response to fibrate drugs, especially between rodents and humans, the latter of which are resistant to fibrate-induced cancer. Fenofibrate metabolism, which also shows species differences, has not been fully determined in humans and surrogate primates. In the present study, the metabolism of fenofibrate was investigated in cynomolgus monkeys by ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOFMS)-based metabolomics. Urine samples were collected before and after oral doses of fenofibrate. The samples were analyzed in both positive-ion and negative-ion modes by UPLC-QTOFMS, and after data deconvolution, the resulting data matrices were subjected to multivariate data analysis. Pattern recognition was performed on the retention time, mass/charge ratio, and other metabolite-related variables. Synthesized or purchased authentic compounds were used for metabolite identification and structure elucidation by liquid chromatographytandem mass spectrometry. Several metabolites were identified, including fenofibric acid, reduced fenofibric acid, fenofibric acid ester glucuronide, reduced fenofibric acid ester glucuronide, and compound X. Another two metabolites (compound B and compound AR), not previously reported in other species, were characterized in cynomolgus monkeys. More importantly, previously unknown metabolites, fenofibric acid taurine conjugate and reduced fenofibric acid taurine conjugate were identified, revealing a previously unrecognized conjugation pathway for fenofibrate.
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PMID:Fenofibrate metabolism in the cynomolgus monkey using ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry-based metabolomics. 1925 19

Metabolic syndrome is a collection of cardiometabolic risk factors that includes obesity, insulin resistance, hypertension and dyslipidemia. Although there has been significant debate regarding the criteria and concept of the syndrome, this clustering of risk factors is unequivocally linked to an increased risk of developing type 2 diabetes and cardiovascular disease. Metabolic syndrome is often characterized by oxidative stress, a condition in which an imbalance results between the production and inactivation of reactive oxygen species. Reactive oxygen species can best be described as double-edged swords; while they play an essential role in multiple physiological systems, under conditions of oxidative stress, they contribute to cellular dysfunction. Oxidative stress is thought to play a major role in the pathogenesis of a variety of human diseases, including atherosclerosis, diabetes, hypertension, aging, Alzheimer's disease, kidney disease and cancer. The purpose of this review is to discuss the role of oxidative stress in metabolic syndrome and its major clinical manifestations (namely coronary artery disease, hypertension and diabetes). It will also highlight the effects of lifestyle modification in ameliorating oxidative stress in metabolic syndrome. Discussion will be limited to human data.
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PMID:Oxidative stress and metabolic syndrome. 1928 26

Nutritional genomics forms part of the genomic sciences and addresses the interaction between genes and the human diet, its influence on metabolism and subsequent susceptibility to develop common diseases. It encompasses both nutrigenomics, which explores the effects of nutrients on the genome, proteome and metabolome; and nutrigenetics, that explores the effects of genetic variations on the diet/disease interaction. A number of mechanisms drive the gene/diet interaction: elements in the diet can act as links for transcription factor receptors and after intermediary concentrations, thereby modifying chromatin and impacting genetic regulation; affect signal pathways, regulating phosphorylation of tyrosine in receptors; decrease signaling through the inositol pathway; and act through epigenetic mechanisms, silencing DNA fragments by methylation of cytosine. The signals generated by polyunsaturated fatty acids are so powerful that they can even bypass insulin mediated lipogenesis, stimulated by carbohydrates. Some fatty acids modify the expression of genes that participate in fatty acid transport by lipoproteins. Nutritional genomics has myriad possible therapeutic and preventive applications: in patients with enzymatic deficiencies; in those with a genetic predisposition to complex diseases such as dyslipidemia, diabetes and cancer; in those that already suffer these diseases; in those with altered mood or memory; during the aging process; in pregnant women; and as a preventive measure in the healthy population.
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PMID:[Nutritional genomics: an approach to the genome-environment interaction]. 1930 79

Obesity is a major risk factor in the development of conditions such as hypertension, hyperglycemia, dyslipidemia, coronary artery disease, and cancer. Several pieces of evidence across different species, including primates, underscore the implication of the histamine 3 receptor (H(3)R) in the regulation of food intake and body weight and the potential therapeutic effect of H(3)R inverse agonists. A pharmacophore model, based on public information and validated by previous investigations, was used to design several potential scaffolds. Out of these scaffolds, the 5-hydroxyindole-2-carboxylic acid amide appeared to be of great potential as a novel series of H(3)R inverse agonist. Extensive structure-activity relationships revealed the interconnectivity of microsomal clearance and hERG (human ether-a-go-go-related gene) affinity with lipophilicity, artificial membrane permeation, and basicity. This effort led to the identification of compounds reversing the (R)-alpha-methylhistamine-induced water intake increase in Wistar rats and, further, reducing food intake in diet-induced obese Sprague-Dawley rats. Of these, the biochemical, pharmacokinetic, and pharmacodynamic characteristics of (4,4-difluoropiperidin-1-yl)[1-isopropyl-5-(1-isopropylpiperidin-4-yloxy)-1H-indol-2-yl]methanone 36 are detailed.
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PMID:5-hydroxyindole-2-carboxylic acid amides: novel histamine-3 receptor inverse agonists for the treatment of obesity. 1945 97

Good nutrition is vital to overall health, and poor diet and a sedentary lifestyle are major causes of morbidity and mortality worldwide. Nutritional factors are implicated in many oral and systemic diseases and conditions, including obesity, hypertension, dyslipidemia, type II diabetes, cardiovascular disease, osteoporosis, dental caries and some cancers including oral cancers. This review focuses on the evidence for the relations between key nutritional factors and health. Energy intake is related to body weight and obesity, highlighting the importance of lower-energy diets and regular physical activity for body weight maintenance and for preventing obesity. Evidence is presented for the health benefits of high quality carbohydrates, such as whole grain products, and fruits and vegetables, in reducing the risk of cardiovascular disease and cancer. The adverse effects of sugar, sweetened beverages, and trans and saturated fats on several diseases including caries, diabetes and cardiovascular disease are described. The health benefits of unsaturated fats, antioxidants, B vitamins and vitamin D in cardiovascular disease, periodontitis, cancer, and other conditions are documented. Both benefits and harmful effects of dairy product intake on health are discussed. Based on the evidence, nutritional guidelines are provided, as well as key recommendations for preventing obesity. Dentists can play a critical role in motivating and enabling healthy food choices.
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PMID:Nutrition and health: guidelines for dental practitioners. 1946 51

Helicobacter pylori (H pylori) infection is a leading world-wide infectious disease as it affects more than half of the world population and causes chronic gastritis, peptic ulcer disease and gastric malignancies. The infection elicits a chronic cellular inflammatory response in the gastric mucosa. However, the effects of this local inflammation may not be confined solely to the digestive tract but may spread to involve extra-intestinal tissues and/or organs. Indeed, H pylori infection has been epidemiologically linked to extra-digestive conditions and diseases. In this context, it has been speculated that H pylori infection may be responsible for various endocrine disorders, such as autoimmune thyroid diseases, diabetes mellitus, dyslipidemia, obesity, osteoporosis and primary hyperparathyroidism. This is a review of the relationship between H pylori infection and these endocrine disorders.
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PMID:Helicobacter pylori infection and endocrine disorders: is there a link? 1952 19

Fatty acid synthase (FAS), an essential enzyme for de novo lipogenesis, has been implicated in a number of disease states, including obesity, dyslipidemia, and cancer. To identify small-molecule inhibitors of FAS, the authors developed a bead-based scintillation proximity assay (SPA) to detect the fatty acid products of FAS enzymatic activity. This homogeneous SPA assay discriminates between a radiolabeled hydrophilic substrate of FAS (acetyl-coenzyme A) and the labeled lipophilic products of FAS (fatty acids), generating signal only when labeled fatty acids are present. The assay requires a single addition of unmodified polystyrene imaging SPA beads and can be miniaturized to 384- or 1536-well density with appropriate assay statistics for high-throughput screening. High-potency FAS inhibitors were used to compare the sensitivity of the SPA bead assay with previously described assays that measure FAS reaction intermediates (CoA-SH and NADP+). The advantages and disadvantages of these different FAS assays in small-molecule inhibitor discovery are discussed.
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PMID:A simplified scintillation proximity assay for fatty acid synthase activity: development and comparison with other FAS activity assays. 1953 64

The metabolic syndrome, characterized by abdominal obesity, high blood glucose levels, impaired glucose tolerance, dyslipidemia, and hypertension, is associated with increased risk of type 2 diabetes and coronary heart disease. Several studies have examined the association of the individual components of the metabolic syndrome with breast cancer; to date, however, no study has assessed the metabolic syndrome per se in relation to breast cancer risk. Furthermore, previous studies have relied only on baseline assessment of components of the syndrome. Therefore, we assessed the association of the metabolic syndrome with the risk of postmenopausal breast cancer among women in the 6% sample of subjects in the Women's Health Initiative clinical trial and the 1% sample of women in the observational study who had repeated measurements of the components of the syndrome during follow-up. We used Cox proportional hazards models to estimate hazard ratios and 95% confidence intervals for the association of breast cancer risk with the presence of the metabolic syndrome, as well as its components, at baseline and in time-dependent analyses. After exclusion of women with diabetes, among 4,888 women with baseline measurements, 165 incident cases of breast cancer were ascertained over a median of 8 years of follow-up. The presence of the metabolic syndrome at baseline was not associated with altered risk. Of the individual components measured at baseline, diastolic blood pressure showed a borderline positive association with breast cancer. In time-dependent covariate analyses, however, certain scenarios indicated a positive association between the metabolic syndrome and breast cancer, due primarily to positive associations with serum glucose, serum triglycerides, and diastolic blood pressure.
Cancer Epidemiol Biomarkers Prev 2009 Jul
PMID:A longitudinal study of the metabolic syndrome and risk of postmenopausal breast cancer. 1956 2

A 31-year-old man with no significant medical history presented with a 5-day history of progressive left upper quadrant abdominal pain. Physical examination revealed a tender guarded abdomen, no icterus, and bilateral corneal "arcus senilis"-like changes. Laboratory workup showed a mild normocytic, normochromic anemia; and target cells were seen in the peripheral blood smear. Serum was turbid; and the lipid profile showed elevated total cholesterol, low high-density lipoprotein cholesterol, and elevated triglycerides. Urinalysis revealed nephrotic range proteinuria with microhematuria. An abdominal computed tomographic scan demonstrated a homogeneously enlarged spleen. The patient was discharged after symptomatic treatment to be followed as an ambulatory patient. Several days later, he returned with severe left upper quadrant pain and was admitted to the surgical service for further evaluation. A splenectomy was performed for a suspected splenic lymphoma. Upon gross examination, spleen was moderately enlarged, weighing 780 g. Sectioning revealed a beefy red cut surface without gross lesions. Wright-Giemsa-stained touch imprints showed many sea-blue histiocytes. A renal biopsy was also performed, demonstrating focal segmental glomerular sclerosis and mesangial expansion with extramembranous and intramembranous deposition of lipids. In the absence of hematologic malignancy and in light of the abnormal lipid profile, a disorder of lipid metabolism was suspected. Histologic and ultrastructural findings in the kidney and spleen raised the likelihood of lecithin-cholesterol acyltransferase (LCAT) deficiency, which was confirmed by the markedly decreased serum LCAT activity and serum LCAT mass. We describe a case with the triad of splenomegaly with sea-blue histiocytes, nephropathy, and dyslipidemia in a patient with LCAT deficiency.
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PMID:Splenomegaly with sea-blue histiocytosis, dyslipidemia, and nephropathy in a patient with lecithin-cholesterol acyltransferase deficiency: a clinicopathologic correlation. 1959 52


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