Excess weight mediates changes in HDL pool that reduce cholesterol efflux capacity and increase antioxidant activity

Objective Obesity-related decline in high-density lipoprotein (HDL) functions such as cholesterol efflux capacity (CEC) has supported the notion that this lipoprotein dysfunction may contribute for atherogenesis among obese patients. Besides, potentially other HDL protective actions may be affected with weight gain and these changes may occur even before the obesity range. Methods Lipid profile, body mass index (BMI), biochemical measurements, and carotid intima-media thickness (cIMT) were obtained in this cross-sectional study with 899 asymptomatic individuals. HDL functions were measured in a subgroup (n=101). Results Individuals with increased HDL-C had an attenuated increase in cIMT with elevation of BMI. CEC, HDL-C, HDL size and HDL-antioxidant activity were negatively associated with cIMT. BMI was inversely associated with HDL-mediated inhibition of platelet aggregation and CEC, but surprisingly it was directly associated with the antioxidant activity. Thus, even in non-obese, non-diabetic individuals, increased BMI is associated with a wide change in protective functions of HDL, reducing CEC and increasing antioxidant activity. In these subjects, decreased HDL concentration, size or function are related to increased atherosclerotic burden. Conclusion Our findings demonstrate that in non-obese, non-diabetic individuals, the increasing values of BMI are associated with impaired protective functions of HDL and concomitant increase in atherosclerotic burden. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial NCT02487615 and [NCT02106013][1] ### Funding Statement The study was supported by São Paulo Research Foundation (FAPESP 2010/00201-8 and FAPESP 2006/60585-9 and CNPq (471380/2008-13). JCLJ was supported by a doctoral grant from Coordination for the Improvement of Higher-Level Education Personnel (Capes grant number PROEX0092045). NBP was supported by a doctoral grant (number 2012/01645-2) from the Foundation for Research Support of the State of Sao Paulo (FAPESP). Prof Sposito was supported by a fellowship grant of productivity in research from the National Council for Scientific and Technological Development (CNPq) (grant number 301465/2017-7). ### Author Declarations All relevant ethical guidelines have been followed and any necessary IRB and/or ethics committee approvals have been obtained. Yes All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes Any clinical trials involved have been registered with an ICMJE-approved registry such as ClinicalTrials.gov and the trial ID is included in the manuscript. Yes I have followed all appropriate research reporting guidelines and uploaded the relevant Equator, ICMJE or other checklist(s) as supplementary files, if applicable. Yes The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request. * ALT : alanine aminotransferase ApoA-I : apolipoprotein A-I AST : aspartate aminotransferase CE : cholesteryl ester CEC : Cholesterol efflux capacity CETP : cholesteryl ester transfer protein cIMT : carotid intima-media thickness FC : free cholesterol HL : hepatic lipase HOMA2 % β : Homeostasis model assessment 2 of beta-cell function HOMA2-IR : Homeostasis model assessment 2 of insulin resistance HOMA2 %S : Homeostasis model assessment 2 of insulin sensitivity HUVEC : human umbilical vein endothelial cells LCAT : Lecithin–cholesterol acyltransferase activity PL : phospholipidis LPL : Lipoprotein lipase PON : paraoxonase TC : total cholesterol PLTP : phospholipids transfer protein VCAM-1 : vascular cell adhesion molecule-1 [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02106013&atom=%2Fmedrxiv%2Fearly%2F2019%2F07%2F24%2F19002899.atom