Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lipoprotein-associated phospholipase (Lp-PL)A2 is a recently described and potentially useful plasma biomarker associated with cardiovascular disease. The enzyme, originally named platelet-activating factor acetylhydrolase (PAF-AH), has two prominent biological activities. First, it inactivates the prominent proinflammatory mediator PAF-AH. Second, Lp-PLA2 hydrolyzes oxidatively modified polyunsaturated fatty acids producing lysophosphatidylcholine (LysoPC) and oxidized nonesterified fatty acids (OxNEFA). OxNEFA have potent monocyte chemotactic activity and LysoPC upregulates inflammatory mediators, including cytokines, adhesion molecules and the chemotactic mediator MCP-1. Whereas the first activity may be considered antiatherogenic, the prevailing consensus is that Lp-PLA2 is positively associated with coronary disease. Initial evidence for this came largely from the West of Scotland Coronary Prevention Study Group (WOSCOPS) in which Lp-PLA2 was compared among 580 cases and 1160 age-matched controls. In addition, the quantitative contribution of Lp-PLA2 to risk assessment was assessed in a substudy of the Atherosclerosis Risk in Communities (ARIC) study. Although positively correlated with disease, the addition of Lp-PLA2 did not appreciably enhance risk prediction beyond the model employing traditional risk factors. Thus, population screening for subclinical disease using Lp-PLA2 does not appear to be warranted. Presently, the most useful application of Lp-PLA2 testing is to adjust individual risk assessment for those patients found to be at borderline risk using traditional models. In this regard, the marker appears to be particularly useful for gauging risk among patients with metabolic syndrome or diabetes. There is observational evidence that Lp-PLA2 may be a useful guide for therapeutic efficacy, but prospective evaluation will be required. Considering the large number of biomarkers currently under evaluation, it is probable that useful additions to existing risk models may be found in combinatorial models.
Expert Rev Mol Diagn 2007 Sep
PMID:Lipoprotein-associated phospholipase A2: a new biomarker for cardiovascular risk assessment and potential therapeutic target. 1789 60

Dietary fatty acids play an important role in the development of insulin resistance, the prelude to type 2 diabetes mellitus. This review addresses the potential role of olive oil-derived MUFA in insulin sensitivity, particularly how dietary fat interacts with insulin resistance looking at whole body metabolic measures, as well as molecular effects. The review focuses on the role of non-esterified fatty acids, fatty acid composition in vivo and dietary fat modification on insulin resistance in the metabolic syndrome. Particular emphasis is placed on the role of olive oil within the context of dietary modification to improve insulin sensitivity and for the prevention of the metabolic syndrome.
Mol Nutr Food Res 2007 Oct
PMID:The potential role of olive oil-derived MUFA in insulin sensitivity. 1791 22

In Mediterranean countries people would previously have consumed a diet with a high proportion of MUFA. Physical activity would have been intense with a low level of stress. The stearoyl-CoA desaturase (SCD1) system selected over thousands of years of this type of behavior must have adapted to a particular capacity of self regulation. Now, this pattern, called the "Mediterranean diet", has been broken and many people living by the Mediterranean consume a high quantity of calories, mainly from saturated or n-6-rich fats and the relative intake of MUFA has decreased. Simultaneously, physical activity has decreased and the pattern of stress has changed towards what is called a western lifestyle. In this new context, if people have a favorable, genetically conditioned SCD1 activity that will let them confront the new situation or else have some other compensatory mechanism, such as being keen on sport, etc, then they can prevent the appearance of some of the complications associated with the metabolic syndrome. If, on the other hand, the SCD1 pattern is genetically unfavorable for this new situation and they have a new cultural context, then they do not have the alternative compensatory mechanisms and the probability of developing the metabolic syndrome is high.
Mol Nutr Food Res 2007 Oct
PMID:Obesity and the metabolic syndrome in Mediterranean countries: a hypothesis related to olive oil. 1791 23

An important sex difference in body fat distribution is generally observed. Men are usually characterized by the android type of obesity, with accumulation of fat in the abdominal region, whereas women often display the gynoid type of obesity, with a greater proportion of their body fat in the gluteal-femoral region. Accordingly, the amount of fat located inside the abdominal cavity (intra-abdominal or visceral adipose tissue) is twice as high in men compared to women. This sex difference has been shown to explain a major portion of the differing metabolic profiles and cardiovascular disease risk in men and women. Association studies have shown that circulating androgens are negatively associated with intra-abdominal fat accumulation in men, which explains an important portion of the link between low androgens and features of the metabolic syndrome. In women, the low circulating sex hormone-binding globulin (SHBG) levels found in abdominal obesity may indirectly indicate that elevated free androgens are related to increased visceral fat accumulation. However, data on non SHBG-bound and total androgens are not unanimous and difficult to interpret for total androgens. These studies focusing on plasma levels of sex hormones indirectly suggest that androgens may alter adipose tissue mass in a depot-specific manner. This could occur through site-specific modulation of preadipocyte proliferation and/or differentiation as well as lipid synthesis and/or lipolysis in mature adipocytes. Recent results on the effects of androgens in cultured adipocytes and adipose tissue have been inconsistent, but may indicate decreased adipogenesis and increased lipolysis upon androgen treatment. Finally, adipose tissue has been shown to express several steroidogenic and steroid-inactivating enzymes. Their mere presence in fat indirectly supports the notion of a highly complex enzymatic system modulating steroid action on a local basis. Recent data obtained in both men and women suggest that enzymes from the aldoketoreductase 1C family are very active and may be important modulators of androgen action in adipose tissue.
J Steroid Biochem Mol Biol 2008 Feb
PMID:Androgens and body fat distribution. 1794 84

Cannabinoid system is a crucial mechanism in regulating food intake and energy metabolism. It is involved in central and peripheral mechanisms regulating such behavior, interacting with many other signaling systems with a role in metabolic regulation. Cannabinoid agonists promote food intake, and soon a cannabinoid antagonist, rimonabant, will be marketed for the treatment of obesity. It not only causes weight loss, but also alleviates metabolic syndrome. We present a review of current knowledge on this subject, along with data from our own research: genetic studies on this system in eating disorders and obesity and studies locating cannabinoid receptors in areas related to food intake. Such studies suggest cannabinoid hyperactivity in obesity, and this excessive activity may have prognostic implications.
Mol Neurobiol 2007 Aug
PMID:Cannabinoids in eating disorders and obesity. 1795 56

The prostaglandin E synthase 2 (PTGES2) gene maps to a locus linked to obesity and is involved in the synthesis of the antilipolytic compound prostaglandin E(2). In a recent study, we found an association of the minor PTGES2 Arg298His allele and lower risk of type 2 diabetes mellitus in the European Investigation into Cancer and Nutrition (EPIC) and Cooperative Health Research in the Augsburg Region (KORA) cohorts. Here, we employed our Metabolic Intervention Cohort Kiel (MICK) to assess the influence of the PTGES2 Arg298His polymorphism on a wider scale of parameters of the metabolic syndrome and postprandial metabolism. In comparison to subjects homozygous for the Arg allele, carriers of the His-allele showed significantly lower fasting insulin (geometric mean +/- SEM: 11.8 muU/mL, 11.41-12.25 versus 13.0, 12.71-13.33; p = 0.023), lower postprandial insulin levels after an oral glucose tolerance test (area under the curve 77.2, 74.07-80.52 versus 81.2, 78.8-83.63; p = 0.023) and lower homeostasis model assessment (HOMA)-insulin-resistance (3.030, 2.909-3.157 versus 3.346, 3.257-3.438; p = 0.041) and HOMA-beta-cell-function (107.2, 104.04-110.52 versus 117.2, 114.65-119.71; p = 0.019). Adjustment for body mass index (BMI) resulted in a loss of these significant differences. BMI tended to show lower values in His-allele carriers, (p = 0.067). In conclusion, risk-reducing effects of the minor His allele of the PTGES2 Arg298His polymorphism could be mediated partly by lowered BMI.
Mol Nutr Food Res 2007 Dec
PMID:Prostaglandin E synthase 2 (PTGES2) Arg298His polymorphism and parameters of the metabolic syndrome. 1797 97

Nonalcoholic fatty liver disease (NAFLD) is a consequence of insulin resistance encompassing a spectrum that extends from simple hepatic steatosis through to nonalcoholic steatohepatitis (NASH), a condition that may progress to cirrhosis with its associated complications. A subset of nuclear receptors act as intracellular sensors for cholesterol metabolites, free fatty acids, and a range of other lipophilic molecules with pivotal roles in energy homeostasis and inflammation. These receptors represent attractive drug targets for the management of NAFLD and NASH as well as related conditions such as type 2 diabetes and the broader metabolic syndrome. To date, human studies have concentrated on peroxisome proliferator-activated receptor (PPAR) agonists, particularly those directed at PPARgamma. However, these drugs have significant limitations, so alternate approaches to nuclear receptor targeting are being explored.
Mol Pharm
PMID:Nonalcoholic fatty liver disease: pathogenesis and potential for nuclear receptors as therapeutic targets. 1807 23

Obesity and dyslipidemia are often found in association with insulin resistance (IR). These components combined with hypertension characterize the most common endocrine disorder in humans, the metabolic syndrome. Thus, in addition to profiling body weight evolution and lipid metabolites, glucose tolerance (a reflection of IR) and insulin sensitivity should also be considered as part of any metabolic phenotyping protocol. The ability to measure IR and glucose tolerance is important not only in the quest to fully understand the pathogenesis of the metabolic syndrome in the mouse, but also to test the effects of potential interventions. This unit presents a variety of tests used for this purpose, including direct blood glucose measurements, insulin measurement by ELISA, the homeostatic model assessment, glucose tolerance and insulin sensitivity tests, and the euglycemic clamp.
Curr Protoc Mol Biol 2007 Jan
PMID:Evaluation of glucose homeostasis. 1826 3

Subtle metabolic changes precede and accompany chronic vascular complications, which are the primary causes of premature death in diabetes. To obtain a multimetabolite characterization of these high-risk individuals, we measured proton nuclear magnetic resonance (1H NMR) data from the serum of 613 patients with type I diabetes and a diverse spread of complications. We developed a new metabonomics framework to visualize and interpret the data and to link the metabolic profiles to the underlying diagnostic and biochemical variables. Our results indicate complex interactions between diabetic kidney disease, insulin resistance and the metabolic syndrome. We illustrate how a single 1H NMR protocol is able to identify the polydiagnostic metabolite manifold of type I diabetes and how its alterations translate to clinical phenotypes, clustering of micro- and macrovascular complications, and mortality during several years of follow-up. This work demonstrates the diffuse nature of complex vascular diseases and the limitations of single diagnostic biomarkers. However, it also promises cost-effective solutions through high-throughput analytics and advanced computational methods, as applied here in a case that is representative of the real clinical situation.
Mol Syst Biol 2008
PMID:1H NMR metabonomics approach to the disease continuum of diabetic complications and premature death. 1827 83

A region along chromosome 7q was recently linked to components of the metabolic syndrome (MetS) in several genome-wide linkage studies. Within this region, the CD36 gene, which encodes a membrane receptor for long-chain fatty acids and lipoproteins, is a potentially important candidate. CD36 has been documented to play an important role in fatty acid metabolism in vivo and subsequently may be involved in the etiology of the MetS. The protein also impacts survival to malaria and the influence of natural selection has resulted in high CD36 genetic variability in populations of African descent. We evaluated 36 tag SNPs across CD36 in the HyperGen population sample of 2020 African-Americans for impact on the MetS and its quantitative traits. Five SNPs associated with increased odds for the MetS [P = 0.0027-0.03, odds ratio (OR) = 1.3-1.4]. Coding SNP, rs3211938, previously shown to influence malaria susceptibility, is documented to result in CD36 deficiency in a homozygous subject. This SNP conferred protection against the MetS (P = 0.0012, OR = 0.61, 95%CI: 0.46-0.82), increased high-density lipoprotein cholesterol, HDL-C (P = 0.00018) and decreased triglycerides (P = 0.0059). Fifteen additional SNPs associated with HDL-C (P = 0.0028-0.044). We conclude that CD36 variants may impact MetS pathophysiology and HDL metabolism, both predictors of the risk of heart disease and type 2 diabetes.
Hum Mol Genet 2008 Jun 01
PMID:Variants in the CD36 gene associate with the metabolic syndrome and high-density lipoprotein cholesterol. 1830 38


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