Obesity Affects HDL Metabolism, Composition and Subclass Distribution.

Julia T Stadler,Willibald Wonisch,Andrea Borenich,Gunther Marsche,Sabrina Mörkl,Sandra J Holasek,Sonja Lackner,Sieglinde Zelzer,Athina Trakaki,Hubert Scharnagl,Nathalie Meier-Allard,Harald Mangge

doi:10.3390/biomedicines9030242

Julia T Stadler, Willibald Wonisch + Show 10 more

Open Access

https://doi.org/10.3390/biomedicines9030242

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Journal: Biomedicines	Publication Date: Feb 27, 2021
Citations: 36	License type: CC BY 4.0

Affiliation: Medical University of Graz, BioTechMed-Graz

Abstract

Background: Obesity increases the risk of coronary heart disease, partly due to its strong association with atherogenic dyslipidemia, characterized by high triglycerides and low high-density lipoprotein (HDL) cholesterol levels. Functional impairment of HDL may contribute to the increased cardiovascular mortality, but the effect of obesity on composition, structure, and function of HDL is not well understood. Design and Methods: We determined HDL composition, HDL subclass distribution, parameters of HDL function, and activities of most important enzymes involved in lipoprotein remodeling, including lecithin–cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) in relatively young normal weight (n = 26), overweight (n = 22), and obese (n = 20) women. Results: Obesity (body mass index (BMI) ≥ 30) was associated with noticeable changes in LCAT and CETP activities and altered HDL composition, such as decreased apolipoprotein A-I, cholesterol, and phospholipid content, while pro-inflammatory HDL serum amyloid a content was increased. We observed a marked shift towards smaller HDL subclasses in obesity linked to lower anti-oxidative capacity of serum. LCAT activity, HDL subclass distribution, and HDL-cholesterol were associated with soluble leptin receptor, adiponectin, and liver enzyme activities. Of note, most of these alterations were only seen in obese women but not in overweight women. Conclusions: Obesity markedly affects HDL metabolism, composition, and subclass distribution linked to changes in liver and adipose tissue. HDL dysfunction may contribute to increased cardiovascular risk in obesity.

Highlights

We observed substantially lower levels of high-density lipoprotein (HDL)-associated free cholesterol, cholesteryl-esters, and phospholipids in the obese group compared to the normal weight group (Figure 1A–C), while there was a trend towards increased HDL triglyceride content (p = 0.055) (Figure 1D)
We provide evidence that obesity significantly affects HDL metabolism, subclass composition, and distribution in association with changes in liver and adipose tissue
Alterations in HDL metabolism, structure, and function in obesity could contribute to increased cardiovascular risk

Summary

Introduction

Reduced plasma levels of HDL-C, but increased triglyceride levels are often observed in obese individuals [7], together with an imbalance of adipokines, such as leptin and adiponectin [8]. Both peptide hormones are produced by adipose tissue and play an important role in the regulation of energy metabolism [9]. The most efficient treatment for low HDL-C levels in morbidly obese patients is bariatric surgery [12,13] This surgical procedure leads to a remarkable increase in plasma HDL-C levels, and to improved HDL function, independent of body weight [11,14,15]. HDL dysfunction may contribute to increased cardiovascular risk in obesity

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Conclusion