Franziska Grundler , Marcella Palumbo , Maria Pia Adorni , Francesca Zimetti , Bianca Papotti , Dietmar Plonné , Alfred Holley , Robin Mesnage , Massimiliano Ruscica , Françoise Wilhelmi de Toledo
{"title":"长期禁食的高密度脂蛋白胆固醇外流能力和胆固醇负荷能力:一项针对健康人的前瞻性单臂干预研究提供的证据","authors":"Franziska Grundler , Marcella Palumbo , Maria Pia Adorni , Francesca Zimetti , Bianca Papotti , Dietmar Plonné , Alfred Holley , Robin Mesnage , Massimiliano Ruscica , Françoise Wilhelmi de Toledo","doi":"10.1016/j.atherosclerosis.2024.118548","DOIUrl":null,"url":null,"abstract":"<div><h3>Background and aims</h3><p>Long-term fasting (LF) is increasingly emerging as a non-pharmacological approach to modulate risk factors associated with the development of atherosclerotic cardiovascular diseases (ASCVD). However, protection from ASCVD is more tied to the functionality of high-density lipoprotein (HDL) than its plasma levels. Our prospective interventional study focuses on the functional properties of lipoproteins in modulating cholesterol homeostasis on peripheral cells and examines how LF may influence this and lipoprotein subclass composition. For that purpose, we investigated its impact on HDL-cholesterol efflux capacity (CEC), and on serum cholesterol loading capacity (CLC).</p></div><div><h3>Methods</h3><p>Forty healthy subjects (50 % females) underwent medically supervised 9-day fasting (250 kcal/day) in a specialised facility. Thirty-two subjects had a follow-up examination after one month of food reintroduction.</p></div><div><h3>Results</h3><p>LF was well tolerated and increased self-reported energy levels. Fasting reduced triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and HDL cholesterol (HDL-C). Very-low-density lipoprotein cholesterol (VLDL-C) and LDL3-C showed sustained reductions at follow-up. Only HDL-C, specifically HDL2-C levels, increased at follow-up. Total HDL-CEC decreased during LF and increased above baseline at follow-up. Fasting decreased ATP binding cassette (ABC)A1-mediated HDL-CEC whereas ABCG1-mediated HDL-CEC remained unaffected. Aqueous diffusion increased at follow up. LF decreased serum CLC and then returned to baseline levels.</p></div><div><h3>Conclusions</h3><p>LF not only maintains lipoprotein functionality but also contributes to a favorable shift in the atherogenic risk profile, which persists even after food reintroduction. This further emphasizes the importance of considering HDL functionality alongside traditional lipid measurements to understand the potential for non-pharmacological interventions like LF to promote cardiovascular prevention and health.</p></div><div><h3>Trial registration number</h3><p>NCT05031598.</p></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"397 ","pages":"Article 118548"},"PeriodicalIF":4.9000,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"HDL cholesterol efflux capacity and cholesterol loading capacity in long-term fasting: Evidence from a prospective, single-arm interventional study in healthy individuals\",\"authors\":\"Franziska Grundler , Marcella Palumbo , Maria Pia Adorni , Francesca Zimetti , Bianca Papotti , Dietmar Plonné , Alfred Holley , Robin Mesnage , Massimiliano Ruscica , Françoise Wilhelmi de Toledo\",\"doi\":\"10.1016/j.atherosclerosis.2024.118548\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background and aims</h3><p>Long-term fasting (LF) is increasingly emerging as a non-pharmacological approach to modulate risk factors associated with the development of atherosclerotic cardiovascular diseases (ASCVD). However, protection from ASCVD is more tied to the functionality of high-density lipoprotein (HDL) than its plasma levels. Our prospective interventional study focuses on the functional properties of lipoproteins in modulating cholesterol homeostasis on peripheral cells and examines how LF may influence this and lipoprotein subclass composition. For that purpose, we investigated its impact on HDL-cholesterol efflux capacity (CEC), and on serum cholesterol loading capacity (CLC).</p></div><div><h3>Methods</h3><p>Forty healthy subjects (50 % females) underwent medically supervised 9-day fasting (250 kcal/day) in a specialised facility. Thirty-two subjects had a follow-up examination after one month of food reintroduction.</p></div><div><h3>Results</h3><p>LF was well tolerated and increased self-reported energy levels. Fasting reduced triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and HDL cholesterol (HDL-C). Very-low-density lipoprotein cholesterol (VLDL-C) and LDL3-C showed sustained reductions at follow-up. Only HDL-C, specifically HDL2-C levels, increased at follow-up. Total HDL-CEC decreased during LF and increased above baseline at follow-up. Fasting decreased ATP binding cassette (ABC)A1-mediated HDL-CEC whereas ABCG1-mediated HDL-CEC remained unaffected. Aqueous diffusion increased at follow up. LF decreased serum CLC and then returned to baseline levels.</p></div><div><h3>Conclusions</h3><p>LF not only maintains lipoprotein functionality but also contributes to a favorable shift in the atherogenic risk profile, which persists even after food reintroduction. This further emphasizes the importance of considering HDL functionality alongside traditional lipid measurements to understand the potential for non-pharmacological interventions like LF to promote cardiovascular prevention and health.</p></div><div><h3>Trial registration number</h3><p>NCT05031598.</p></div>\",\"PeriodicalId\":8623,\"journal\":{\"name\":\"Atherosclerosis\",\"volume\":\"397 \",\"pages\":\"Article 118548\"},\"PeriodicalIF\":4.9000,\"publicationDate\":\"2024-08-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Atherosclerosis\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S002191502401116X\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CARDIAC & CARDIOVASCULAR SYSTEMS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Atherosclerosis","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S002191502401116X","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
HDL cholesterol efflux capacity and cholesterol loading capacity in long-term fasting: Evidence from a prospective, single-arm interventional study in healthy individuals
Background and aims
Long-term fasting (LF) is increasingly emerging as a non-pharmacological approach to modulate risk factors associated with the development of atherosclerotic cardiovascular diseases (ASCVD). However, protection from ASCVD is more tied to the functionality of high-density lipoprotein (HDL) than its plasma levels. Our prospective interventional study focuses on the functional properties of lipoproteins in modulating cholesterol homeostasis on peripheral cells and examines how LF may influence this and lipoprotein subclass composition. For that purpose, we investigated its impact on HDL-cholesterol efflux capacity (CEC), and on serum cholesterol loading capacity (CLC).
Methods
Forty healthy subjects (50 % females) underwent medically supervised 9-day fasting (250 kcal/day) in a specialised facility. Thirty-two subjects had a follow-up examination after one month of food reintroduction.
Results
LF was well tolerated and increased self-reported energy levels. Fasting reduced triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and HDL cholesterol (HDL-C). Very-low-density lipoprotein cholesterol (VLDL-C) and LDL3-C showed sustained reductions at follow-up. Only HDL-C, specifically HDL2-C levels, increased at follow-up. Total HDL-CEC decreased during LF and increased above baseline at follow-up. Fasting decreased ATP binding cassette (ABC)A1-mediated HDL-CEC whereas ABCG1-mediated HDL-CEC remained unaffected. Aqueous diffusion increased at follow up. LF decreased serum CLC and then returned to baseline levels.
Conclusions
LF not only maintains lipoprotein functionality but also contributes to a favorable shift in the atherogenic risk profile, which persists even after food reintroduction. This further emphasizes the importance of considering HDL functionality alongside traditional lipid measurements to understand the potential for non-pharmacological interventions like LF to promote cardiovascular prevention and health.
期刊介绍:
Atherosclerosis has an open access mirror journal Atherosclerosis: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review.
Atherosclerosis brings together, from all sources, papers concerned with investigation on atherosclerosis, its risk factors and clinical manifestations. Atherosclerosis covers basic and translational, clinical and population research approaches to arterial and vascular biology and disease, as well as their risk factors including: disturbances of lipid and lipoprotein metabolism, diabetes and hypertension, thrombosis, and inflammation. The Editors are interested in original or review papers dealing with the pathogenesis, environmental, genetic and epigenetic basis, diagnosis or treatment of atherosclerosis and related diseases as well as their risk factors.