Association of serum retinol binding protein 4 with atherogenic dyslipidemia in morbid obese patients.

Milagros Rocha,Eva Solá,Lorena Bellod,Víctor M Víctor,Celia Bañuls,Antonio Hernández-Mijares,Carlos Morillas,Susana Rovira-Llopis,Cedric Moro

doi:10.1371/journal.pone.0078670

Abstract

Retinol binding protein 4 (RBP4) is an adipokine that may contribute to the development of insulin resistance. However, how this adipokine is affected and its possible involvement in lipid metabolism in obese patients with varying degrees of insulin resistance is yet to be determined. A total of 299 middle-aged morbid obese patients (BMI>40 kg/m2) were divided in euglycemic, metabolic syndrome or type 2 diabetic. Anthropometric measurements, biochemical variables and systemic RBP4 levels were determined. RBP4 levels were significantly higher in patients with metabolic syndrome and type 2 diabetes than in euglycemic subjects (42.9±14.6; 42.3±17.0 and 37.4±11.7 µg/ml, respectively) and correlated with triglycerides but not with those of HOMA-IR in the whole population. The multivariate regression model revealed that triglycerides were the strongest predictor of systemic RBP4 levels. Analysis of lipoprotein subfractions in a subpopulation of 80 subjects showed an altered profile of insulin resistant states characterized by higher VLDL, sdLDL and small HDL percentages and lower large HDL percentage. Although RBP4 levels correlated significantly with LDL particle size and small HDL percentage, the latter parameter was independently associated only with RBP4. Our study reveals that systemic RBP4 levels could play an important role in lipid metabolism in morbid obesity, increasing triglyceride levels and contributing to the formation of small HDL.

Highlights

Obesity is a prevalent condition characterized by the excessive accumulation and storage of fat in adipose tissue
When the distribution of Retinol binding protein 4 (RBP4) was assessed according to gender, we found it to be significantly higher in men than in women (45.1615.6 mg/ml versus 39.3613.4 mg/ml, p,0.0001, respectively)
The current study provides evidence that serum RBP4 levels are higher in middle-aged morbid obese subjects with metabolic syndrome (MetS) and type 2 diabetes (T2D) than in euglycemic ones

Summary

Introduction

Obesity is a prevalent condition characterized by the excessive accumulation and storage of fat in adipose tissue It is a major cause of insulin resistance, which is implicated in the development of metabolic syndrome (MetS) and type 2 diabetes (T2D). The two major quantitative lipid abnormalities in these patients are increased triglyceride levels and low high-density lipoprotein (HDL) levels When these parameters are associated with a higher proportion of small and dense low-density lipoprotein particles (sdLDL), atherogenic dyslipidemia is diagnosed. This condition has emerged as an important marker of the increased cardiovascular disease risk observed in patients with obesity, MetS, insulin resistance and T2D [3]. In common metabolic diseases, such as T2D and MetS, it seems that HDL atherogenicity increases as particle size decreases, and that small HDL particles are more atherogenic than large HDL [4]

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