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      Unacylated Ghrelin is associated with the isolated low HDL-cholesterol obese phenotype independently of insulin resistance and CRP level

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          Abstract

          Background

          Low plasma high-density lipoprotein-cholesterol (HDL-c) level is commonly present in obesity and represents an independent cardiovascular risk factor. However, obese patients are a very heterogeneous population and the factors and mechanisms that contribute to low HDL-c remain unclear. The aim of this study was to investigate the association between plasma HDL-c levels and plasma hormonal profiles (insulin, adiponectin, resistin, leptin and ghrelin) in subsets of class II and III obese patients.

          Methods

          Fasting plasma levels of glucose, total cholesterol, LDL-c, HDL-c, triglycerides, free fatty acids, apoproteins A-I, B-100, B-48, C-II, C-III, insulin, hs-CRP, adipocytokines (adiponectin, resistin, leptin), unacylated ghrelin, body composition (DXA) and resting energy expenditure were measured in three subsets of obese patients: 17 metabolically abnormal obese (MAO) with metabolic syndrome and the typical metabolic dyslipidaemia, 21 metabolically healthy obese (MHO) without metabolic syndrome and with a normal lipid profile, and 21 isolated low HDL-c obese patients (LHO) without metabolic syndrome, compared to 21 healthy lean control subjects.

          Results

          Insulin resistance (HOMA-IR) increased gradually from MHO to LHO and from LHO to MAO patients ( p < 0.05 between MHO and MAO and between LHO and MAO). In multiple regression analysis, serum unacylated ghrelin levels were only positively and independently associated with HDL-c levels in the LHO group ( p = 0.032).

          Conclusions

          These results suggest that, in class II and III obese patients with an isolated low HDL-c phenotype, unacylated ghrelin is positively associated with HDL-c level independently of insulin resistance and CRP levels, and may contribute to the highly prevalent low HDL-c level seen in obesity.

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          Most cited references23

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          Overproduction of very low-density lipoproteins is the hallmark of the dyslipidemia in the metabolic syndrome.

          Insulin resistance is a key feature of the metabolic syndrome and often progresses to type 2 diabetes. Both insulin resistance and type 2 diabetes are characterized by dyslipidemia, which is an important and common risk factor for cardiovascular disease. Diabetic dyslipidemia is a cluster of potentially atherogenic lipid and lipoprotein abnormalities that are metabolically interrelated. Recent evidence suggests that a fundamental defect is an overproduction of large very low-density lipoprotein (VLDL) particles, which initiates a sequence of lipoprotein changes, resulting in higher levels of remnant particles, smaller LDL, and lower levels of high-density liporotein (HDL) cholesterol. These atherogenic lipid abnormalities precede the diagnosis of type 2 diabetes by several years, and it is thus important to elucidate the mechanisms involved in the overproduction of large VLDL particles. Here, we review the pathophysiology of VLDL biosynthesis and metabolism in the metabolic syndrome. We also review recent research investigating the relation between hepatic accumulation of lipids and insulin resistance, and sources of fatty acids for liver fat and VLDL biosynthesis. Finally, we briefly discuss current treatments for lipid management of dyslipidemia and potential future therapeutic targets.
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            Preferential fat deposition in subcutaneous versus visceral depots is associated with insulin sensitivity.

            Studies on the relationship between regional fat and insulin resistance yield mixed results. Our objective was to determine whether regional fat distribution, independent of obesity, is associated with insulin resistance. Subjects included 115 healthy, overweight/moderately obese adults with body mass index (BMI) 25-36.9 kg/m(2) who met predetermined criteria for being insulin resistant (IR) or insulin sensitive (IS) based on the modified insulin suppression test. Computerized tomography was used to quantify visceral adipose tissue (VAT), sc adipose tissue (SAT), and thigh adipose tissue. Fat mass in each depot was compared according to IR/IS group, adjusting for BMI and sex. Despite nearly identical mean BMI in the IR vs. IS groups, VAT and %VAT were significantly higher in the IR group, whereas SAT, %SAT, and thigh sc fat were significantly lower. In logistic regression analysis, each sd increase in VAT increased the odds of being IR by 80%, whereas each increase in SAT decreased the odds by 48%; each increase in thigh fat decreased the odds by 59% and retained significance after adjusting for other depots. When grouped by VAT tertile, IS vs. IR individuals had significantly more SAT. There was no statistically significant interaction between sex and these relationships. These data demonstrate that after adjustment for BMI and VAT mass, sc abdominal and thigh fat are protective for insulin resistance, whereas VAT, after adjustment for SAT and BMI, has the opposite effect. Whether causal in nature or a marker of underlying pathology, these results clarify that regional distribution of fat-favoring sc depots is associated with lower risk for insulin resistance.
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              Visceral obesity: the link among inflammation, hypertension, and cardiovascular disease.

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                Author and article information

                Journal
                Nutr Metab (Lond)
                Nutr Metab (Lond)
                Nutrition & Metabolism
                BioMed Central
                1743-7075
                2012
                13 March 2012
                : 9
                : 17
                Affiliations
                [1 ]Aix-Marseille Univ, UMR 1260, 13005 Marseille, France
                [2 ]UMR INSERM 939, La Pitié Hospital, Paris, France
                [3 ]Aix-Marseille Univ, APHM, Sainte Marguerite Hospital, Department of Biochemistry, 13005 Marseille, France
                [4 ]Aix-Marseille Univ, APHM, La Timone Hospital, Department of Digestive Surgery, 13005 Marseille, France
                [5 ]Aix-Marseille Univ, APHM, La Timone Hospital, Department of Nutrition, Metabolic diseases, Endocrinology, 13005 Marseille, France
                [6 ]Aix-Marseille Univ, EA 3283, Biostatistics Research Unit, Laboratory of Education and Research in Medical Information Processing (LERTIM), 13005 Marseille, France
                [7 ]Service de Nutrition, Maladies métaboliques et Endocrinologie, Hôpital La Timone, 264 Rue Saint Pierre, 13005 Marseille, France
                Article
                1743-7075-9-17
                10.1186/1743-7075-9-17
                3317856
                22413940
                52d9cb2f-3f8c-498e-9e4a-fde71bc9ea92
                Copyright ©2012 Nogueira et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 21 October 2011
                : 13 March 2012
                Categories
                Research

                Nutrition & Dietetics
                ghrelin,obesity,lipids,adiponectin,apolipoprotein,insulin resistance,cardiovascular risk,inflammation,hdl-cholesterol

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