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      Dyslipidemia in Obesity: Mechanisms and Potential Targets

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          Abstract

          Obesity has become a major worldwide health problem. In every single country in the world, the incidence of obesity is rising continuously and therefore, the associated morbidity, mortality and both medical and economical costs are expected to increase as well. The majority of these complications are related to co-morbid conditions that include coronary artery disease, hypertension, type 2 diabetes mellitus, respiratory disorders and dyslipidemia. Obesity increases cardiovascular risk through risk factors such as increased fasting plasma triglycerides, high LDL cholesterol, low HDL cholesterol, elevated blood glucose and insulin levels and high blood pressure. Novel lipid dependent, metabolic risk factors associated to obesity are the presence of the small dense LDL phenotype, postprandial hyperlipidemia with accumulation of atherogenic remnants and hepatic overproduction of apoB containing lipoproteins. All these lipid abnormalities are typical features of the metabolic syndrome and may be associated to a pro-inflammatory gradient which in part may originate in the adipose tissue itself and directly affect the endothelium. An important link between obesity, the metabolic syndrome and dyslipidemia, seems to be the development of insulin resistance in peripheral tissues leading to an enhanced hepatic flux of fatty acids from dietary sources, intravascular lipolysis and from adipose tissue resistant to the antilipolytic effects of insulin. The current review will focus on these aspects of lipid metabolism in obesity and potential interventions to treat the obesity related dyslipidemia.

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          Most cited references133

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          Obesity, insulin resistance and free fatty acids.

          To describe the role of free fatty acid (FFA) as a cause for insulin resistance in obese people. Elevated plasma FFA levels can account for a large part of insulin resistance in obese patients with type 2 diabetes. Insulin resistance is clinically important because it is closely associated with several diseases including type 2 diabetes, hypertension, dyslipidemia and abnormalities in blood coagulation and fibrinolysis. These disorders are all independent risk factors for cardiovascular disease (heart attacks, strokes and peripheral arterial disease). The mechanisms by which FFA can cause insulin resistance, although not completely known, include generation of lipid metabolites (diacylglycerol), proinflammatory cytokines (TNF-α, IL-1β, IL-6, MCP1) and cellular stress including oxidative and endoplasmic reticulum stress. Increased plasma FFA levels are an important cause of obesity-associated insulin resistance and cardiovascular disease. Therapeutic application of this knowledge is hampered by the lack of readily accessible methods to measure FFA and by the lack of medications to lower plasma FFA levels.
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            Waist circumference as a measure for indicating need for weight management.

            To test the hypothesis that a single measurement, waist circumference, might be used to identify people at health risk both from being overweight and from having a central fat distribution. A community derived random sample of men and women and a second, validation sample. North Glasgow. 904 men and 1014 women (first sample); 86 men and 202 women (validation sample). Waist circumference, body mass index, waist:hip ratio. Waist circumference > or = 94 cm for men and > or = 80 cm for women identified subjects with high body mass index (> or = 25 kg/m2) and those with lower body mass index but high waist:hip ratio (> or = 0.95 for men, > or = 0.80 women) with a sensitivity of > 96% and specificity > 97.5%. Waist circumference > or = 102 cm for men or > or = 88 cm for women identified subjects with body mass index > or = 30 and those with lower body mass index but high waist:hip ratio with a sensitivity of > 96% and specificity > 98%, with only about 2% of the sample being misclassified. Waist circumference could be used in health promotion programmes to identify individuals who should seek and be offered weight management. Men with waist circumference > or = 94 cm and women with waist circumference > or = 80 cm should gain no further weight; men with waist circumference > or = 102 cm and women with waist circumference > or = 88 cm should reduce their weight.
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              A meta-analysis of low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B as markers of cardiovascular risk.

              Whether apolipoprotein B (apoB) or non-high-density lipoprotein cholesterol (HDL-C) adds to the predictive power of low-density lipoprotein cholesterol (LDL-C) for cardiovascular risk remains controversial. This meta-analysis is based on all the published epidemiological studies that contained estimates of the relative risks of non-HDL-C and apoB of fatal or nonfatal ischemic cardiovascular events. Twelve independent reports, including 233 455 subjects and 22 950 events, were analyzed. All published risk estimates were converted to standardized relative risk ratios (RRRs) and analyzed by quantitative meta-analysis using a random-effects model. Whether analyzed individually or in head-to-head comparisons, apoB was the most potent marker of cardiovascular risk (RRR, 1.43; 95% CI, 1.35 to 1.51), LDL-C was the least (RRR, 1.25; 95% CI, 1.18 to 1.33), and non-HDL-C was intermediate (RRR, 1.34; 95% CI, 1.24 to 1.44). The overall comparisons of the within-study differences showed that apoB RRR was 5.7%>non-HDL-C (P LDL-C (P LDL-C (P=0.017). Only HDL-C accounted for any substantial portion of the variance of the results among the studies. We calculated the number of clinical events prevented by a high-risk treatment regimen of all those >70th percentile of the US adult population using each of the 3 markers. Over a 10-year period, a non-HDL-C strategy would prevent 300 000 more events than an LDL-C strategy, whereas an apoB strategy would prevent 500 000 more events than a non-HDL-C strategy. These results further validate the value of apoB in clinical care.
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                12 April 2013
                April 2013
                : 5
                : 4
                : 1218-1240
                Affiliations
                Department of Internal Medicine, Diabetes and Vascular Centre, Sint Franciscus Gasthuis, Rotterdam, P.O. Box 10900, 3004 BA, The Netherlands; E-Mails: b.klop@ 123456sfg.nl (B.K.); jwfelte@ 123456planet.nl (J.W.F.E.)
                Author notes
                [* ] Author to whom correspondence should be addressed; E-Mail: m.castrocabezas@ 123456sfg.nl ; Tel.: +31-10-461-7267; Fax: +31-10-461-2692.
                Article
                nutrients-05-01218
                10.3390/nu5041218
                3705344
                23584084
                0e3c876f-2086-4800-9f92-83d438f40408
                © 2013 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                : 21 December 2012
                : 14 February 2013
                : 27 March 2013
                Categories
                Review

                Nutrition & Dietetics
                free fatty acid,postprandial lipemia,apolipoprotein b,non-hdl-c,small dense ldl,acylation-stimulation protein,statin,fibrate

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