Increasing plant protein in the diet induces changes in the plasma metabolome that may be beneficial for metabolic health. A randomized crossover study in males
Dietary shifts replacing animal protein (AP) with plant protein (PP) sources have been associated with lowering cardiometabolic risk (CMR), but underlying mechanisms are poorly characterized. This nutritional intervention aims to characterize the metabolic changes induced by diets containing differe...
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creator | Lépine, Gaïa Mariotti, François Tremblay-Franco, Marie Courrent, Marion Verny, Marie-Anne David, Jérémie Mathé, Véronique Jame, Patrick Anchisi, Anthony Lefranc-Millot, Catherine Perreau, Caroline Guérin-Deremaux, Laetitia Chollet, Céline Castelli, Florence Chu-Van, Emeline Huneau, Jean-François Rémond, Didier Pickering, Gisèle Fouillet, Hélène Polakof, Sergio |
description | Dietary shifts replacing animal protein (AP) with plant protein (PP) sources have been associated with lowering cardiometabolic risk (CMR), but underlying mechanisms are poorly characterized. This nutritional intervention aims to characterize the metabolic changes induced by diets containing different proportions of AP and PP sources in males at CMR.
This study is a 4-week, crossover, randomized, controlled-feeding trial in which 19 males with CMR followed two diets providing either 36 % for the control diet (CON-D) or 64 % for the flexitarian diet (FLEX-D) of total protein intake from PP sources. Plasma nontargeted metabolomes (LC-MS method) were measured in the fasted state and after a high-fat challenge meal at the end of each intervention arm. Lipogenesis and protein synthesis fluxes, flow-mediated dilatation (FMD) and gluco-lipidic responses were assessed after the challenge meal. Data were analyzed with mixed models, and univariate and multivariate models for metabolomics data.
In both arms CMR improved with time, with decreased body weight (−0.9 %), insulin resistant (−34 %, HOMA-IR, Homeostatic Model Assessment for Insulin Resistance) and low-density lipoproteins (LDL)-cholesterol (−11 %). Diet had no effect on FMD or metabolic fluxes, but a trend (0.05 |
doi_str_mv | 10.1016/j.clnu.2024.10.009 |
format | Article |
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This study is a 4-week, crossover, randomized, controlled-feeding trial in which 19 males with CMR followed two diets providing either 36 % for the control diet (CON-D) or 64 % for the flexitarian diet (FLEX-D) of total protein intake from PP sources. Plasma nontargeted metabolomes (LC-MS method) were measured in the fasted state and after a high-fat challenge meal at the end of each intervention arm. Lipogenesis and protein synthesis fluxes, flow-mediated dilatation (FMD) and gluco-lipidic responses were assessed after the challenge meal. Data were analyzed with mixed models, and univariate and multivariate models for metabolomics data.
In both arms CMR improved with time, with decreased body weight (−0.9 %), insulin resistant (−34 %, HOMA-IR, Homeostatic Model Assessment for Insulin Resistance) and low-density lipoproteins (LDL)-cholesterol (−11 %). Diet had no effect on FMD or metabolic fluxes, but a trend (0.05 <p ≤ 0.1) was observed for a stronger decrease in HOMA-IR and lower postprandial glucose after FLEX-D vs CON-D. The abundance of 21 and 37 metabolites differed between diets at fasted and fed states, respectively, including food intake biomarkers of AP (methylhistidine, eicosapentaenoic acid, hydroxyprolines) and PP sources (trigonelline, N-acetyl-ornithine). In fasted or fed states, indole acrylic acid and indole propionic acid, both products of tryptophan catabolism, were higher after FLEX-D vs CON-D, while the indispensable amino acids-related metabolites alpha-aminoadipic acid, hydroxymethylbutyric acids and propionylcarnitine were lower. In the postprandial state only, the ω-oxidation products dodecanedioic, tetradecanedioic and hexadecanedioic acids were higher after FLEX-D vs CON-D.
Despite little changes in risk factors after 4 wk, this study evidenced subtle metabolic adaptations in amino acids and lipid metabolism and gut microbiota activity occurring after higher PP source intake that may be beneficial to CMR.
NCT04236518.
NCT04236518 on ClinicalTrials.gov.</description><identifier>ISSN: 0261-5614</identifier><identifier>ISSN: 1532-1983</identifier><identifier>EISSN: 1532-1983</identifier><identifier>DOI: 10.1016/j.clnu.2024.10.009</identifier><identifier>PMID: 39454458</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Adult ; Blood Glucose - metabolism ; Branched-chain amino acids ; Cardiometabolic Risk Factors ; Cross-Over Studies ; Diet - methods ; Fasting - blood ; Food and Nutrition ; Humans ; Hypertriglyceridemic waist phenotype ; Insulin Resistance ; Life Sciences ; Male ; Metabolome - physiology ; Middle Aged ; Plant Proteins ; Plant-based diet ; Postprandial Period - physiology ; Postprandial response ; Trimethylamine-oxide ; Young Adult</subject><ispartof>Clinical nutrition (Edinburgh, Scotland), 2024-12, Vol.43 (12), p.146-157</ispartof><rights>2024 The Author(s)</rights><rights>Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c315t-95dbe650f2bcd8864335818d86280749e6f950c22e4e59dcd0b89d049172b1253</cites><orcidid>0000-0002-0976-8732 ; 0000-0003-4678-4456 ; 0009-0005-0428-7031 ; 0000-0002-6886-8549 ; 0000-0001-7336-2617 ; 0000-0003-3932-251X ; 0000-0002-4516-3853 ; 0000-0003-1827-2138 ; 0000-0001-6295-9389 ; 0000-0003-4430-0067</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.clnu.2024.10.009$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,315,781,785,886,3551,27929,27930,46000</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39454458$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.inrae.fr/hal-04769512$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Lépine, Gaïa</creatorcontrib><creatorcontrib>Mariotti, François</creatorcontrib><creatorcontrib>Tremblay-Franco, Marie</creatorcontrib><creatorcontrib>Courrent, Marion</creatorcontrib><creatorcontrib>Verny, Marie-Anne</creatorcontrib><creatorcontrib>David, Jérémie</creatorcontrib><creatorcontrib>Mathé, Véronique</creatorcontrib><creatorcontrib>Jame, Patrick</creatorcontrib><creatorcontrib>Anchisi, Anthony</creatorcontrib><creatorcontrib>Lefranc-Millot, Catherine</creatorcontrib><creatorcontrib>Perreau, Caroline</creatorcontrib><creatorcontrib>Guérin-Deremaux, Laetitia</creatorcontrib><creatorcontrib>Chollet, Céline</creatorcontrib><creatorcontrib>Castelli, Florence</creatorcontrib><creatorcontrib>Chu-Van, Emeline</creatorcontrib><creatorcontrib>Huneau, Jean-François</creatorcontrib><creatorcontrib>Rémond, Didier</creatorcontrib><creatorcontrib>Pickering, Gisèle</creatorcontrib><creatorcontrib>Fouillet, Hélène</creatorcontrib><creatorcontrib>Polakof, Sergio</creatorcontrib><title>Increasing plant protein in the diet induces changes in the plasma metabolome that may be beneficial for metabolic health. A randomized crossover study in males</title><title>Clinical nutrition (Edinburgh, Scotland)</title><addtitle>Clin Nutr</addtitle><description>Dietary shifts replacing animal protein (AP) with plant protein (PP) sources have been associated with lowering cardiometabolic risk (CMR), but underlying mechanisms are poorly characterized. This nutritional intervention aims to characterize the metabolic changes induced by diets containing different proportions of AP and PP sources in males at CMR.
This study is a 4-week, crossover, randomized, controlled-feeding trial in which 19 males with CMR followed two diets providing either 36 % for the control diet (CON-D) or 64 % for the flexitarian diet (FLEX-D) of total protein intake from PP sources. Plasma nontargeted metabolomes (LC-MS method) were measured in the fasted state and after a high-fat challenge meal at the end of each intervention arm. Lipogenesis and protein synthesis fluxes, flow-mediated dilatation (FMD) and gluco-lipidic responses were assessed after the challenge meal. Data were analyzed with mixed models, and univariate and multivariate models for metabolomics data.
In both arms CMR improved with time, with decreased body weight (−0.9 %), insulin resistant (−34 %, HOMA-IR, Homeostatic Model Assessment for Insulin Resistance) and low-density lipoproteins (LDL)-cholesterol (−11 %). Diet had no effect on FMD or metabolic fluxes, but a trend (0.05 <p ≤ 0.1) was observed for a stronger decrease in HOMA-IR and lower postprandial glucose after FLEX-D vs CON-D. The abundance of 21 and 37 metabolites differed between diets at fasted and fed states, respectively, including food intake biomarkers of AP (methylhistidine, eicosapentaenoic acid, hydroxyprolines) and PP sources (trigonelline, N-acetyl-ornithine). In fasted or fed states, indole acrylic acid and indole propionic acid, both products of tryptophan catabolism, were higher after FLEX-D vs CON-D, while the indispensable amino acids-related metabolites alpha-aminoadipic acid, hydroxymethylbutyric acids and propionylcarnitine were lower. In the postprandial state only, the ω-oxidation products dodecanedioic, tetradecanedioic and hexadecanedioic acids were higher after FLEX-D vs CON-D.
Despite little changes in risk factors after 4 wk, this study evidenced subtle metabolic adaptations in amino acids and lipid metabolism and gut microbiota activity occurring after higher PP source intake that may be beneficial to CMR.
NCT04236518.
NCT04236518 on ClinicalTrials.gov.</description><subject>Adult</subject><subject>Blood Glucose - metabolism</subject><subject>Branched-chain amino acids</subject><subject>Cardiometabolic Risk Factors</subject><subject>Cross-Over Studies</subject><subject>Diet - methods</subject><subject>Fasting - blood</subject><subject>Food and Nutrition</subject><subject>Humans</subject><subject>Hypertriglyceridemic waist phenotype</subject><subject>Insulin Resistance</subject><subject>Life Sciences</subject><subject>Male</subject><subject>Metabolome - physiology</subject><subject>Middle Aged</subject><subject>Plant Proteins</subject><subject>Plant-based diet</subject><subject>Postprandial Period - physiology</subject><subject>Postprandial response</subject><subject>Trimethylamine-oxide</subject><subject>Young Adult</subject><issn>0261-5614</issn><issn>1532-1983</issn><issn>1532-1983</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9UcGO0zAUtBCILYUf4IB8hEOK7dipLXGpVsCuVIkLnC3Hftm4SuJiO5W6X8On4tDuHpGe9KzxzFieQeg9JRtKaPP5sLHDNG8YYbwAG0LUC7SiomYVVbJ-iVaENbQSDeU36E1KB0KIqLfyNbqpFRecC7lCf-4nG8EkPz3g42CmjI8xZPATLpN7wM5DLmc3W0jY9mZ6KPt6VwRpNHiEbNowhBEKajIezRm3UGaCzltvBtyF-MTyFvdghtxv8A5HM7kw-kdw2MaQUjhBxCnP7rw8MZoB0lv0qjNDgnfXvUa_vn39eXtX7X98v7_d7StbU5ErJVwLjSAda62TsuF1LSSVTjZMki1X0HRKEMsYcBDKWUdaqRzhim5ZS5mo1-jTxbc3gz5GP5p41sF4fbfb6wUjfNsoQdmJFu7HC7dk9XuGlPXok4Wh5AdhTrqmjBKhWGlhjdiF-u9_Ebpnb0r00qI-6KVFvbS4YKXFIvpw9Z_bEdyz5Km2QvhyIUBJ5OQh6mQ9TBacj2CzdsH_z_8vg_6vGw</recordid><startdate>202412</startdate><enddate>202412</enddate><creator>Lépine, Gaïa</creator><creator>Mariotti, François</creator><creator>Tremblay-Franco, Marie</creator><creator>Courrent, Marion</creator><creator>Verny, Marie-Anne</creator><creator>David, Jérémie</creator><creator>Mathé, Véronique</creator><creator>Jame, Patrick</creator><creator>Anchisi, Anthony</creator><creator>Lefranc-Millot, Catherine</creator><creator>Perreau, Caroline</creator><creator>Guérin-Deremaux, Laetitia</creator><creator>Chollet, Céline</creator><creator>Castelli, Florence</creator><creator>Chu-Van, Emeline</creator><creator>Huneau, Jean-François</creator><creator>Rémond, Didier</creator><creator>Pickering, Gisèle</creator><creator>Fouillet, Hélène</creator><creator>Polakof, Sergio</creator><general>Elsevier Ltd</general><general>Elsevier / European Society for Clinical Nutrition and Metabolism</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>1XC</scope><scope>VOOES</scope><orcidid>https://orcid.org/0000-0002-0976-8732</orcidid><orcidid>https://orcid.org/0000-0003-4678-4456</orcidid><orcidid>https://orcid.org/0009-0005-0428-7031</orcidid><orcidid>https://orcid.org/0000-0002-6886-8549</orcidid><orcidid>https://orcid.org/0000-0001-7336-2617</orcidid><orcidid>https://orcid.org/0000-0003-3932-251X</orcidid><orcidid>https://orcid.org/0000-0002-4516-3853</orcidid><orcidid>https://orcid.org/0000-0003-1827-2138</orcidid><orcidid>https://orcid.org/0000-0001-6295-9389</orcidid><orcidid>https://orcid.org/0000-0003-4430-0067</orcidid></search><sort><creationdate>202412</creationdate><title>Increasing plant protein in the diet induces changes in the plasma metabolome that may be beneficial for metabolic health. A randomized crossover study in males</title><author>Lépine, Gaïa ; Mariotti, François ; Tremblay-Franco, Marie ; Courrent, Marion ; Verny, Marie-Anne ; David, Jérémie ; Mathé, Véronique ; Jame, Patrick ; Anchisi, Anthony ; Lefranc-Millot, Catherine ; Perreau, Caroline ; Guérin-Deremaux, Laetitia ; Chollet, Céline ; Castelli, Florence ; Chu-Van, Emeline ; Huneau, Jean-François ; Rémond, Didier ; Pickering, Gisèle ; Fouillet, Hélène ; Polakof, Sergio</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c315t-95dbe650f2bcd8864335818d86280749e6f950c22e4e59dcd0b89d049172b1253</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adult</topic><topic>Blood Glucose - metabolism</topic><topic>Branched-chain amino acids</topic><topic>Cardiometabolic Risk Factors</topic><topic>Cross-Over Studies</topic><topic>Diet - methods</topic><topic>Fasting - blood</topic><topic>Food and Nutrition</topic><topic>Humans</topic><topic>Hypertriglyceridemic waist phenotype</topic><topic>Insulin Resistance</topic><topic>Life Sciences</topic><topic>Male</topic><topic>Metabolome - physiology</topic><topic>Middle Aged</topic><topic>Plant Proteins</topic><topic>Plant-based diet</topic><topic>Postprandial Period - physiology</topic><topic>Postprandial response</topic><topic>Trimethylamine-oxide</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lépine, Gaïa</creatorcontrib><creatorcontrib>Mariotti, François</creatorcontrib><creatorcontrib>Tremblay-Franco, Marie</creatorcontrib><creatorcontrib>Courrent, Marion</creatorcontrib><creatorcontrib>Verny, Marie-Anne</creatorcontrib><creatorcontrib>David, Jérémie</creatorcontrib><creatorcontrib>Mathé, Véronique</creatorcontrib><creatorcontrib>Jame, Patrick</creatorcontrib><creatorcontrib>Anchisi, Anthony</creatorcontrib><creatorcontrib>Lefranc-Millot, Catherine</creatorcontrib><creatorcontrib>Perreau, Caroline</creatorcontrib><creatorcontrib>Guérin-Deremaux, Laetitia</creatorcontrib><creatorcontrib>Chollet, Céline</creatorcontrib><creatorcontrib>Castelli, Florence</creatorcontrib><creatorcontrib>Chu-Van, Emeline</creatorcontrib><creatorcontrib>Huneau, Jean-François</creatorcontrib><creatorcontrib>Rémond, Didier</creatorcontrib><creatorcontrib>Pickering, Gisèle</creatorcontrib><creatorcontrib>Fouillet, Hélène</creatorcontrib><creatorcontrib>Polakof, Sergio</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><jtitle>Clinical nutrition (Edinburgh, Scotland)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lépine, Gaïa</au><au>Mariotti, François</au><au>Tremblay-Franco, Marie</au><au>Courrent, Marion</au><au>Verny, Marie-Anne</au><au>David, Jérémie</au><au>Mathé, Véronique</au><au>Jame, Patrick</au><au>Anchisi, Anthony</au><au>Lefranc-Millot, Catherine</au><au>Perreau, Caroline</au><au>Guérin-Deremaux, Laetitia</au><au>Chollet, Céline</au><au>Castelli, Florence</au><au>Chu-Van, Emeline</au><au>Huneau, Jean-François</au><au>Rémond, Didier</au><au>Pickering, Gisèle</au><au>Fouillet, Hélène</au><au>Polakof, Sergio</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Increasing plant protein in the diet induces changes in the plasma metabolome that may be beneficial for metabolic health. A randomized crossover study in males</atitle><jtitle>Clinical nutrition (Edinburgh, Scotland)</jtitle><addtitle>Clin Nutr</addtitle><date>2024-12</date><risdate>2024</risdate><volume>43</volume><issue>12</issue><spage>146</spage><epage>157</epage><pages>146-157</pages><issn>0261-5614</issn><issn>1532-1983</issn><eissn>1532-1983</eissn><abstract>Dietary shifts replacing animal protein (AP) with plant protein (PP) sources have been associated with lowering cardiometabolic risk (CMR), but underlying mechanisms are poorly characterized. This nutritional intervention aims to characterize the metabolic changes induced by diets containing different proportions of AP and PP sources in males at CMR.
This study is a 4-week, crossover, randomized, controlled-feeding trial in which 19 males with CMR followed two diets providing either 36 % for the control diet (CON-D) or 64 % for the flexitarian diet (FLEX-D) of total protein intake from PP sources. Plasma nontargeted metabolomes (LC-MS method) were measured in the fasted state and after a high-fat challenge meal at the end of each intervention arm. Lipogenesis and protein synthesis fluxes, flow-mediated dilatation (FMD) and gluco-lipidic responses were assessed after the challenge meal. Data were analyzed with mixed models, and univariate and multivariate models for metabolomics data.
In both arms CMR improved with time, with decreased body weight (−0.9 %), insulin resistant (−34 %, HOMA-IR, Homeostatic Model Assessment for Insulin Resistance) and low-density lipoproteins (LDL)-cholesterol (−11 %). Diet had no effect on FMD or metabolic fluxes, but a trend (0.05 <p ≤ 0.1) was observed for a stronger decrease in HOMA-IR and lower postprandial glucose after FLEX-D vs CON-D. The abundance of 21 and 37 metabolites differed between diets at fasted and fed states, respectively, including food intake biomarkers of AP (methylhistidine, eicosapentaenoic acid, hydroxyprolines) and PP sources (trigonelline, N-acetyl-ornithine). In fasted or fed states, indole acrylic acid and indole propionic acid, both products of tryptophan catabolism, were higher after FLEX-D vs CON-D, while the indispensable amino acids-related metabolites alpha-aminoadipic acid, hydroxymethylbutyric acids and propionylcarnitine were lower. In the postprandial state only, the ω-oxidation products dodecanedioic, tetradecanedioic and hexadecanedioic acids were higher after FLEX-D vs CON-D.
Despite little changes in risk factors after 4 wk, this study evidenced subtle metabolic adaptations in amino acids and lipid metabolism and gut microbiota activity occurring after higher PP source intake that may be beneficial to CMR.
NCT04236518.
NCT04236518 on ClinicalTrials.gov.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>39454458</pmid><doi>10.1016/j.clnu.2024.10.009</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-0976-8732</orcidid><orcidid>https://orcid.org/0000-0003-4678-4456</orcidid><orcidid>https://orcid.org/0009-0005-0428-7031</orcidid><orcidid>https://orcid.org/0000-0002-6886-8549</orcidid><orcidid>https://orcid.org/0000-0001-7336-2617</orcidid><orcidid>https://orcid.org/0000-0003-3932-251X</orcidid><orcidid>https://orcid.org/0000-0002-4516-3853</orcidid><orcidid>https://orcid.org/0000-0003-1827-2138</orcidid><orcidid>https://orcid.org/0000-0001-6295-9389</orcidid><orcidid>https://orcid.org/0000-0003-4430-0067</orcidid><oa>free_for_read</oa></addata></record> |
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ispartof | Clinical nutrition (Edinburgh, Scotland), 2024-12, Vol.43 (12), p.146-157 |
issn | 0261-5614 1532-1983 1532-1983 |
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source | MEDLINE; Access via ScienceDirect (Elsevier) |
subjects | Adult Blood Glucose - metabolism Branched-chain amino acids Cardiometabolic Risk Factors Cross-Over Studies Diet - methods Fasting - blood Food and Nutrition Humans Hypertriglyceridemic waist phenotype Insulin Resistance Life Sciences Male Metabolome - physiology Middle Aged Plant Proteins Plant-based diet Postprandial Period - physiology Postprandial response Trimethylamine-oxide Young Adult |
title | Increasing plant protein in the diet induces changes in the plasma metabolome that may be beneficial for metabolic health. A randomized crossover study in males |
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