High density lipoprotein-associated proteins in non-obese women with and without polycystic ovary syndrome

IntroductionDyslipidemia frequently occurs in women with polycystic ovary syndrome (PCOS), but it is unclear whether dyslipidemia is due to obesity and insulin resistance (IR) or is inherent to PCOS. To address this, proteomic analysis of proteins important in lipid metabolism, particularly for high...

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Main Authors: Alexandra E. Butler, Abu Saleh Md Moin, Željko Reiner, Thozhukat Sathyapalan, Tannaz Jamialahmadi, Amirhossein Sahebkar, Stephen L. Atkin
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-04-01
Series:Frontiers in Endocrinology
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Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2023.1117761/full
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author Alexandra E. Butler
Abu Saleh Md Moin
Željko Reiner
Thozhukat Sathyapalan
Tannaz Jamialahmadi
Amirhossein Sahebkar
Amirhossein Sahebkar
Amirhossein Sahebkar
Amirhossein Sahebkar
Stephen L. Atkin
author_facet Alexandra E. Butler
Abu Saleh Md Moin
Željko Reiner
Thozhukat Sathyapalan
Tannaz Jamialahmadi
Amirhossein Sahebkar
Amirhossein Sahebkar
Amirhossein Sahebkar
Amirhossein Sahebkar
Stephen L. Atkin
author_sort Alexandra E. Butler
collection DOAJ
description IntroductionDyslipidemia frequently occurs in women with polycystic ovary syndrome (PCOS), but it is unclear whether dyslipidemia is due to obesity and insulin resistance (IR) or is inherent to PCOS. To address this, proteomic analysis of proteins important in lipid metabolism, particularly for high-density lipoprotein cholesterol (HDL-C), was performed in non-obese, non-insulin resistant PCOS women compared to matched controls.MethodsWeight and aged-matched non-obese subjects with PCOS (n=24) and without IR were compared with control women (n=24). 19 proteins were measured by Somalogic proteomic analysis: alpha-1-antichymotrypsin, alpha-1-antitrypsin, apolipoproteins A-1, B, D, E, E2, E3, E4, L1, M, clusterin, complement C3, hemopexin, heparin cofactor-II (HCFII), kininogen-1, serum amyloid A-1, amyloid beta A-4 and paraoxonase-1.ResultsWomen with PCOS had a higher free androgen index (FAI) (p<0.001) and anti-Mullerian hormone (AMH) (p<0.001), but IR and C-reactive protein (CRP), a marker of inflammation, did not differ from controls (p>0.05). The triglyceride:HDL-cholesterol ratio was elevated (p=0.03) in PCOS. Alpha-1-antitrypsin levels were lower (p<0.05) and complement C3 levels were higher (p=0.001) in PCOS. C3 correlated with body mass index (BMI) (r=0.59, p=0.001), IR (r=0.63, p=0.0005) and CRP (r=0.42, p=0.04) in women with PCOS, though no correlations of these parameters with alpha-1-antitrypsin were found. Total cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol and levels of the other 17 lipoprotein metabolism-associated proteins did not differ between the two groups (p>0.05). However, in PCOS, alpha-1-antichymotrypsin correlated negatively with BMI (r=-0.40, p<0.04) and HOMA-IR (r=-0.42, p<0.03), apoM correlated positively with CRP (r=0.36, p<0.04) and HCFII correlated negatively with BMI (r=-0.34, p<0.04).ConclusionIn PCOS subjects, when obesity, IR and inflammation confounders were absent, alpha-1-antitrypsin was lower and complement C3 was higher than in non-PCOS women, suggesting increased cardiovascular risk; however, subsequent obesity related IR/inflammation likely stimulates other HDL-associated protein abnormalities, thus increasing cardiovascular risk further.
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spelling doaj.art-3f4af86db3a349fe812ec76ceebf33cd2023-04-26T13:57:54ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-04-011410.3389/fendo.2023.11177611117761High density lipoprotein-associated proteins in non-obese women with and without polycystic ovary syndromeAlexandra E. Butler0Abu Saleh Md Moin1Željko Reiner2Thozhukat Sathyapalan3Tannaz Jamialahmadi4Amirhossein Sahebkar5Amirhossein Sahebkar6Amirhossein Sahebkar7Amirhossein Sahebkar8Stephen L. Atkin9Research Department, Royal College of Surgeons in Ireland Bahrain, Adliya, BahrainResearch Department, Royal College of Surgeons in Ireland Bahrain, Adliya, BahrainDepartment of Internal Medicine, University Hospital Center Zagreb, Zagreb, CroatiaAcademic Endocrinology, Diabetes and Metabolism, Hull York Medical School, Hull, United KingdomApplied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, IranApplied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, IranBiotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, IranSchool of Medicine, The University of Western Australia, Perth, WA, AustraliaDepartment of Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, IranResearch Department, Royal College of Surgeons in Ireland Bahrain, Adliya, BahrainIntroductionDyslipidemia frequently occurs in women with polycystic ovary syndrome (PCOS), but it is unclear whether dyslipidemia is due to obesity and insulin resistance (IR) or is inherent to PCOS. To address this, proteomic analysis of proteins important in lipid metabolism, particularly for high-density lipoprotein cholesterol (HDL-C), was performed in non-obese, non-insulin resistant PCOS women compared to matched controls.MethodsWeight and aged-matched non-obese subjects with PCOS (n=24) and without IR were compared with control women (n=24). 19 proteins were measured by Somalogic proteomic analysis: alpha-1-antichymotrypsin, alpha-1-antitrypsin, apolipoproteins A-1, B, D, E, E2, E3, E4, L1, M, clusterin, complement C3, hemopexin, heparin cofactor-II (HCFII), kininogen-1, serum amyloid A-1, amyloid beta A-4 and paraoxonase-1.ResultsWomen with PCOS had a higher free androgen index (FAI) (p<0.001) and anti-Mullerian hormone (AMH) (p<0.001), but IR and C-reactive protein (CRP), a marker of inflammation, did not differ from controls (p>0.05). The triglyceride:HDL-cholesterol ratio was elevated (p=0.03) in PCOS. Alpha-1-antitrypsin levels were lower (p<0.05) and complement C3 levels were higher (p=0.001) in PCOS. C3 correlated with body mass index (BMI) (r=0.59, p=0.001), IR (r=0.63, p=0.0005) and CRP (r=0.42, p=0.04) in women with PCOS, though no correlations of these parameters with alpha-1-antitrypsin were found. Total cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol and levels of the other 17 lipoprotein metabolism-associated proteins did not differ between the two groups (p>0.05). However, in PCOS, alpha-1-antichymotrypsin correlated negatively with BMI (r=-0.40, p<0.04) and HOMA-IR (r=-0.42, p<0.03), apoM correlated positively with CRP (r=0.36, p<0.04) and HCFII correlated negatively with BMI (r=-0.34, p<0.04).ConclusionIn PCOS subjects, when obesity, IR and inflammation confounders were absent, alpha-1-antitrypsin was lower and complement C3 was higher than in non-PCOS women, suggesting increased cardiovascular risk; however, subsequent obesity related IR/inflammation likely stimulates other HDL-associated protein abnormalities, thus increasing cardiovascular risk further.https://www.frontiersin.org/articles/10.3389/fendo.2023.1117761/fullpolycystic ovary syndromelipidsHDLLDLdyslipidemia
spellingShingle Alexandra E. Butler
Abu Saleh Md Moin
Željko Reiner
Thozhukat Sathyapalan
Tannaz Jamialahmadi
Amirhossein Sahebkar
Amirhossein Sahebkar
Amirhossein Sahebkar
Amirhossein Sahebkar
Stephen L. Atkin
High density lipoprotein-associated proteins in non-obese women with and without polycystic ovary syndrome
Frontiers in Endocrinology
polycystic ovary syndrome
lipids
HDL
LDL
dyslipidemia
title High density lipoprotein-associated proteins in non-obese women with and without polycystic ovary syndrome
title_full High density lipoprotein-associated proteins in non-obese women with and without polycystic ovary syndrome
title_fullStr High density lipoprotein-associated proteins in non-obese women with and without polycystic ovary syndrome
title_full_unstemmed High density lipoprotein-associated proteins in non-obese women with and without polycystic ovary syndrome
title_short High density lipoprotein-associated proteins in non-obese women with and without polycystic ovary syndrome
title_sort high density lipoprotein associated proteins in non obese women with and without polycystic ovary syndrome
topic polycystic ovary syndrome
lipids
HDL
LDL
dyslipidemia
url https://www.frontiersin.org/articles/10.3389/fendo.2023.1117761/full
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