Clin Endocrinol. 2014 Sep;81(3):370-7.

Strong correlations between circulating chemerin levels and lipoprotein subfractions in nondiabetic obese and nonobese subjects.

Lőrincz H, Katkó M, Harangi M, Somodi S, Gaál K, Fülöp P, Paragh G, Seres I.

Division of Metabolic Diseases, Department of Medicine, University of Debrecen Medical and Health Science Center, Debrecen, Hungary.

 

Abstract

OBJECTIVE: Chemerin is a recently described adipokine expressed primarily in the white adipose tissue. Compared with lean subjects, circulating chemerin levels are significantly elevated in obese individuals and correlate positively with the prevalence of various cardiovascular risk factors including altered lipoprotein levels. To date, the impact of chemerin on lipoprotein subfractions and its role in atherosclerotic processes are still unclear.

PATIENTS AND METHODS: Fifty nondiabetic obese (NDO) patients and 38 lean controls matched in age and gender were enrolled. Chemerin level was measured by ELISA. Low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subfractions were detected by nongradient polyacrylamide gel electrophoresis (Lipoprint).

RESULTS: We detected significantly higher serum chemerin levels in NDO patients compared with healthy controls (590·1 ± 190·3 ng/ml vs 405 ± 127·1 ng/ml, P < 0·001). A significant positive correlation was found between chemerin and LDL cholesterol levels, while chemerin showed a significant negative correlation with the level of HDL cholesterol. Significant positive correlation was detected between chemerin and the ratio of small dense LDL, while chemerin correlated negatively with the mean LDL size. Also, a significant negative correlation was found between serum chemerin and the ratio of large HDL subfraction, while there were significant positive correlations between chemerin levels and intermediate and small HDL subfraction ratios, respectively.

CONCLUSION: Chemerin may be involved in the regulation of lipoprotein metabolism in obese patients who do not show apparent abnormalities of glucose metabolism. Early changes in the distribution of the lipoprotein subfractions may contribute to the progression of atherosclerosis, leading to increased cardiovascular risk. © 2013 John Wiley & Sons Ltd.

PMID: 24303851

 

Supplement:

Chemerin is a recently described adipokine expressed primarily by white adipose tissue, liver and kidney. Chemerin has several biological functions as it regulates the innate and adaptive immune system through its receptor (chemokine-like receptor 1 – CMKLR1) and serves as a chemoattractant factor for immature dendritic cells, macrophages and natural killer cells (1). Increased circulating chemerin levels are found in obesity, insulin resistant conditions and associated with various cardiovascular risk factors including dyslipidemias. It is well-known that low-density lipoprotein (LDL) and high-density lipoprotein (HDL) represent heterogeneous populations of particles in respect to size, density and chemical composition (2). Predominantly smaller and denser LDL particles play a key role in the initiation and progression of atherosclerosis (3). In contrast, HDL is considered to act against atherosclerosis. Small-sized HDL subfractions rather exert anti-inflammatory effects against LDL modification compared to large-sized HDL subfractions primarily ascribed to reverse cholesterol transport (4).

To date, the impact of chemerin on lipoprotein subfractions and its role in atherosclerosis are still unclear. Therefore, we studied circulating chemerin levels and the distribution of LDL and HDL subfractions in fifty non-diabetic obese (NDO) subjects (age: 44.2±13.5 yrs, BMI: 41.96±8.63 kg/m2) and compared their data to thirty-eight non-diabetic non-obese individuals (age: 42.26±11.36 yrs, BMI: 24.05±3.21 kg/m2). We also examined the potential associations between serum chemerin levels and lipoprotein subfractions.

High-sensitivity C-reactive protein (hsCRP) and serum chemerin concentrations were significantly elevated in NDO patients compared to normal-weight controls (p<0.001 and p<0.001, respectively). Although there were significant differences in several laboratory parameters between the studied groups, these variables still fell in the physiological range. According to the LDL subfraction analyses, we detected a significantly higher proportion of small-sized and more atherogenic LDL subfraction (p<0.001) and lower mean LDL size (p<0.001) in NDO patients compared to lean controls. Although HDL cholesterol levels were in the normal range in both studied groups, HDL subfraction analyses showed a shift towards the small HDL subfractions in NDO patients compared to healthy controls.

Studying the associations between serum chemerin concentrations and the distribution of lipoprotein subfractions, significant positive correlations were detected between chemerin and LDL cholesterol levels (r=0.34; p=0.0009) and between chemerin level and the proportion of small LDL subfraction (r=0.39; p=0.0003). Furthermore, we found a significant negative association between chemerin level and mean LDL size (r=-0.37; p=0.0008). In contrast, the associations between chemerin levels and HDL subfractions were not uniform. Indeed, serum chemerin level showed significant negative correlations with the HDL cholesterol level (r=-0.24; p=0.02) and the proportion of large HDL subfraction (r=-0.47; p=0.00001); while there were positive associations between chemerin concentration and the proportion of intermediate and small HDL subfractions (r=0.23; p=0.04 and r=0.47; p=0.000008, respectively). Multivariate analyses showed that hsCRP and small HDL subfractions were the best independent predictors of chemerin.

We conclude that chemerin may be involved in the regulation of lipoprotein metabolism in non-diabetic obese patients. Despite normal lipid levels, we observed unfavorable and atherogenic LDL and HDL subfraction profiles in these subjects that may also result in structural and functional alterations. Therefore, early changes in the distribution of lipoprotein subfractions may contribute to enhanced atherogenesis and increased cardiovascular risk. Early screening and treatment of these lipid abnormalities would help to reduce the risk of cardiovascular events and might improve the mortality and morbidity of these patients.

Figure_Lorincz

References:

  1. Mattern A, Zellmann T, Beck-Sickinger AG. Processing, signaling, and physiological function of chemerin. IUBMB Life. 2014;66:19-26.
  2. Krauss RM. Lipoprotein subfractions and cardiovascular disease risk. Curr Opin Lipidol. 2010;21:305-311.
  3. Mertens A, Holvoet P. Oxidized LDL and HDL: antagonists in atherothrombosis. FASEB J. 2001;15:2073-2084.
  4. Kontush A, Chapman MJ. Antiatherogenic small, dense HDL-guardian angel of the arterial wall? Nat Clin Pract Cardiovasc Med. 2006;3:144-153.

 

Acknowledgments:

The work is supported by a grant from the Hungarian Scientific Research Fund (OTKA 84196) and by the TÁMOP-4.2.2.A-11/1/KONV-2012-0031 project. The TÁMOP project is co-financed by the European Union and the European Social Fund.

 

Contact:

Ildikó Seres, PhD

Division of Metabolic Diseases

University of Debrecen, Faculty of Medicine, Hungary

Nagyerdei krt. 98., H-4032 Debrecen, Hungary

E-mail: seres@belklinika.com

 

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