Obesity Affects HDL Metabolism, Composition and Subclass Distribution

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.

Human Fecal Metabolome Reflects Differences in Body Mass Index, Physical Fitness, and Blood Lipoproteins in Healthy Older Adults

“…Similar to the findings of Trimigno et al, Pasiakos et al reported that lower-BMI subjects have higher HDLchol levels at high-protein diets [51], which indicates that high-BMI subjects potentially have a higher risk of CVD as HDLchol is recognized as good cholesterol [52]. The higher risk of CVD for overweight subjects has also been related to impaired HDLchol metabolism [53]. Schmedes et al concluded that weight loss decreases both the levels of LP in plasma and SCFA in fecal samples [54].…”

Dietary Strategies to Improve Cardiovascular Health: Focus on Increasing High-Density Lipoprotein Functionality

“…However, several chronic diseases are associated with profound alterations in HDL metabolism and function, caused by increased systemic oxidative stress and inflammation ( 12 , 54 ). These conditions include obesity ( 55 – 57 ), chronic kidney disease ( 58 , 59 ), liver disease ( 60 , 61 ), diabetes ( 62 – 64 ), CVD ( 65 , 66 ), but also allergic rhinitis ( 67 ) and skin diseases ( 68 , 69 ). Compositional modifications and concomitant changes in parameters of HDL function may lead to development of pro-atherogenic characteristics and enhancement of the inflammatory state.…”

Anti-inflammatory function of apolipoprotein B-depleted plasma is impaired in non-alcoholic fatty liver disease

“…It has been shown that obesity affected the lipid composition of HDL particles, increased acute phase protein serum amyloid a, and altered HDL particle subpopulations. Moreover, HDL of obese subjects showed prooxidative properties [ 25 ]. Because of higher obesity indices values in the NAFLD group and a significant relationship between impaired anti-inflammatory capacity of apoB-depleted plasma and obesity indices in the current study, we sought to determine if the association between impaired HDL anti-inflammatory capacity and NAFLD is related to obesity.…”