Adropin expression reflects circadian, lipoprotein, and mitochondrial processes in human tissues

The clinical significance of interindividual variation in circulating adropin levels is unclear. To better understand adropin biology at the whole-body level, we surveyed transcriptional structures co-regulated with the Energy Homeostasis Associated (ENHO) gene encoding adropin across human tissues...

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Main Authors: Joseph R. Stevens, Clemence Girardet, Mingqi Zhou, Farah Gamie, Geetika Aggarwal, Ryan P. McMillan, Matthew W. Hulver, Laurent O. Martinez, Marcel van der Brug, Bruno Vellas, Andrew D. Nguyen, Marcus M. Seldin, Andrew A. Butler, MAPT Study Group, Principal investigator, Coordination, Sophie Guyonnet, Project leader, Isabelle Carrié, CRA, Lauréane Brigitte, Investigators, Catherine Faisant, Françoise Lala, Julien Delrieu, Hélène Villars, Psychologists, Emeline Combrouze, Carole Badufle, Audrey Zueras, Methodology, statistical analysis and data management, Sandrine Andrieu, Christelle Cantet, Christophe Morin, Multidomain group, Gabor Abellan Van Kan, Charlotte Dupuy, Yves Rolland, Céline Caillaud, Pierre-Jean Ousset, Co-Investigators in associated centres, Jean-François Dartigues, Isabelle Marcet, Fleur Delva, Alexandra Foubert, Sandrine Cerda, Marie-Noëlle Cuffi, Corinne Costes, Olivier Rouaud, Patrick Manckoundia, Valérie Quipourt, Sophie Marilier, Evelyne Franon, Lawrence Bories, Marie-Laure Pader, Marie-France Basset, Bruno Lapoujade, Valérie Faure, Michael Li Yung Tong, Christine Malick-Loiseau, Evelyne Cazaban-Campistron, Françoise Desclaux, Colette Blatge, Thierry Dantoine, Cécile Laubarie-Mouret, Isabelle Saulnier, Jean-Pierre Clément, Marie-Agnès Picat, Laurence Bernard-Bourzeix, Stéphanie Willebois, Iléana Désormais, Noëlle Cardinaud, Marc Bonnefoy, Pierre Livet, Pascale Rebaudet, Claire Gédéon, Catherine Burdet, Flavien Terracol, Alain Pesce, Stéphanie Roth, Sylvie Chaillou, Sandrine Louchart, Kristel Sudres, Nicolas Lebrun, Nadège Barro-Belaygues, Jacques Touchon, Karim Bennys, Audrey Gabelle, Aurélia Romano, Lynda Touati, Cécilia Marelli, Cécile Pays, Philippe Robert, Franck Le Duff, Claire Gervais, Sébastien Gonfrier, Yannick Gasnier, Serge Bordes, Danièle Begorre, Christian Carpuat, Khaled Khales, Jean-François Lefebvre, Samira Misbah El Idrissi, Pierre Skolil, Jean-Pierre Salles, MRI group, Carole Dufouil, Stéphane Lehéricy, Marie Chupin, Jean-François Mangin, Ali Bouhayia, Michèle Allard, Frédéric Ricolfi, Dominique Dubois, Marie Paule Bonceour Martel, François Cotton, Alain Bonafé, Stéphane Chanalet, Françoise Hugon, Fabrice Bonneville, Christophe Cognard, François Chollet, PET scans group, Pierre Payoux, Thierry Voisin, Sophie Peiffer, Anne Hitzel, Michel Zanca, Jacques Monteil, Jacques Darcourt, Medico-economics group, Laurent Molinier, Hélène Derumeaux, Nadège Costa, Biological sample collection, Bertrand Perret, Claire Vinel, Sylvie Caspar-Bauguil, Safety management, Pascale Olivier-Abbal, IHU Open Science Group, Nicola Coley
Format: Article
Language:English
Published: Elsevier 2025-09-01
Series:Molecular Metabolism
Online Access:http://www.sciencedirect.com/science/article/pii/S2212877825001036
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author Joseph R. Stevens
Clemence Girardet
Mingqi Zhou
Farah Gamie
Geetika Aggarwal
Ryan P. McMillan
Matthew W. Hulver
Laurent O. Martinez
Marcel van der Brug
Bruno Vellas
Andrew D. Nguyen
Marcus M. Seldin
Andrew A. Butler
MAPT Study Group
Principal investigator
Bruno Vellas
Coordination
Sophie Guyonnet
Project leader
Isabelle Carrié
CRA
Lauréane Brigitte
Investigators
Catherine Faisant
Françoise Lala
Julien Delrieu
Hélène Villars
Psychologists
Emeline Combrouze
Carole Badufle
Audrey Zueras
Methodology, statistical analysis and data management
Sandrine Andrieu
Christelle Cantet
Christophe Morin
Multidomain group
Gabor Abellan Van Kan
Charlotte Dupuy
Yves Rolland
Céline Caillaud
Pierre-Jean Ousset
Françoise Lala
Co-Investigators in associated centres
Jean-François Dartigues
Isabelle Marcet
Fleur Delva
Alexandra Foubert
Sandrine Cerda
Marie-Noëlle Cuffi
Corinne Costes
Olivier Rouaud
Patrick Manckoundia
Valérie Quipourt
Sophie Marilier
Evelyne Franon
Lawrence Bories
Marie-Laure Pader
Marie-France Basset
Bruno Lapoujade
Valérie Faure
Michael Li Yung Tong
Christine Malick-Loiseau
Evelyne Cazaban-Campistron
Françoise Desclaux
Colette Blatge
Thierry Dantoine
Cécile Laubarie-Mouret
Isabelle Saulnier
Jean-Pierre Clément
Marie-Agnès Picat
Laurence Bernard-Bourzeix
Stéphanie Willebois
Iléana Désormais
Noëlle Cardinaud
Marc Bonnefoy
Pierre Livet
Pascale Rebaudet
Claire Gédéon
Catherine Burdet
Flavien Terracol
Alain Pesce
Stéphanie Roth
Sylvie Chaillou
Sandrine Louchart
Kristel Sudres
Nicolas Lebrun
Nadège Barro-Belaygues
Jacques Touchon
Karim Bennys
Audrey Gabelle
Aurélia Romano
Lynda Touati
Cécilia Marelli
Cécile Pays
Philippe Robert
Franck Le Duff
Claire Gervais
Sébastien Gonfrier
Yannick Gasnier
Serge Bordes
Danièle Begorre
Christian Carpuat
Khaled Khales
Jean-François Lefebvre
Samira Misbah El Idrissi
Pierre Skolil
Jean-Pierre Salles
MRI group
Carole Dufouil
Stéphane Lehéricy
Marie Chupin
Jean-François Mangin
Ali Bouhayia
Michèle Allard
Frédéric Ricolfi
Dominique Dubois
Marie Paule Bonceour Martel
François Cotton
Alain Bonafé
Stéphane Chanalet
Françoise Hugon
Fabrice Bonneville
Christophe Cognard
François Chollet
PET scans group
Pierre Payoux
Thierry Voisin
Julien Delrieu
Sophie Peiffer
Anne Hitzel
Michèle Allard
Michel Zanca
Jacques Monteil
Jacques Darcourt
Medico-economics group
Laurent Molinier
Hélène Derumeaux
Nadège Costa
Biological sample collection
Bertrand Perret
Claire Vinel
Sylvie Caspar-Bauguil
Safety management
Pascale Olivier-Abbal
IHU Open Science Group
Nicola Coley
Sandrine Andrieu
Christelle Cantet
Sophie Guyonnet
author_facet Joseph R. Stevens
Clemence Girardet
Mingqi Zhou
Farah Gamie
Geetika Aggarwal
Ryan P. McMillan
Matthew W. Hulver
Laurent O. Martinez
Marcel van der Brug
Bruno Vellas
Andrew D. Nguyen
Marcus M. Seldin
Andrew A. Butler
MAPT Study Group
Principal investigator
Bruno Vellas
Coordination
Sophie Guyonnet
Project leader
Isabelle Carrié
CRA
Lauréane Brigitte
Investigators
Catherine Faisant
Françoise Lala
Julien Delrieu
Hélène Villars
Psychologists
Emeline Combrouze
Carole Badufle
Audrey Zueras
Methodology, statistical analysis and data management
Sandrine Andrieu
Christelle Cantet
Christophe Morin
Multidomain group
Gabor Abellan Van Kan
Charlotte Dupuy
Yves Rolland
Céline Caillaud
Pierre-Jean Ousset
Françoise Lala
Co-Investigators in associated centres
Jean-François Dartigues
Isabelle Marcet
Fleur Delva
Alexandra Foubert
Sandrine Cerda
Marie-Noëlle Cuffi
Corinne Costes
Olivier Rouaud
Patrick Manckoundia
Valérie Quipourt
Sophie Marilier
Evelyne Franon
Lawrence Bories
Marie-Laure Pader
Marie-France Basset
Bruno Lapoujade
Valérie Faure
Michael Li Yung Tong
Christine Malick-Loiseau
Evelyne Cazaban-Campistron
Françoise Desclaux
Colette Blatge
Thierry Dantoine
Cécile Laubarie-Mouret
Isabelle Saulnier
Jean-Pierre Clément
Marie-Agnès Picat
Laurence Bernard-Bourzeix
Stéphanie Willebois
Iléana Désormais
Noëlle Cardinaud
Marc Bonnefoy
Pierre Livet
Pascale Rebaudet
Claire Gédéon
Catherine Burdet
Flavien Terracol
Alain Pesce
Stéphanie Roth
Sylvie Chaillou
Sandrine Louchart
Kristel Sudres
Nicolas Lebrun
Nadège Barro-Belaygues
Jacques Touchon
Karim Bennys
Audrey Gabelle
Aurélia Romano
Lynda Touati
Cécilia Marelli
Cécile Pays
Philippe Robert
Franck Le Duff
Claire Gervais
Sébastien Gonfrier
Yannick Gasnier
Serge Bordes
Danièle Begorre
Christian Carpuat
Khaled Khales
Jean-François Lefebvre
Samira Misbah El Idrissi
Pierre Skolil
Jean-Pierre Salles
MRI group
Carole Dufouil
Stéphane Lehéricy
Marie Chupin
Jean-François Mangin
Ali Bouhayia
Michèle Allard
Frédéric Ricolfi
Dominique Dubois
Marie Paule Bonceour Martel
François Cotton
Alain Bonafé
Stéphane Chanalet
Françoise Hugon
Fabrice Bonneville
Christophe Cognard
François Chollet
PET scans group
Pierre Payoux
Thierry Voisin
Julien Delrieu
Sophie Peiffer
Anne Hitzel
Michèle Allard
Michel Zanca
Jacques Monteil
Jacques Darcourt
Medico-economics group
Laurent Molinier
Hélène Derumeaux
Nadège Costa
Biological sample collection
Bertrand Perret
Claire Vinel
Sylvie Caspar-Bauguil
Safety management
Pascale Olivier-Abbal
IHU Open Science Group
Nicola Coley
Sandrine Andrieu
Christelle Cantet
Sophie Guyonnet
author_sort Joseph R. Stevens
collection DOAJ
description The clinical significance of interindividual variation in circulating adropin levels is unclear. To better understand adropin biology at the whole-body level, we surveyed transcriptional structures co-regulated with the Energy Homeostasis Associated (ENHO) gene encoding adropin across human tissues using Gene-Derived Correlations Across Tissues (GD-CAT). ENHO/adropin-related transcriptional structures with >1000 genes meeting the selection threshold (q < 0.001) occurred in 11/20 tissues. While most reflect local relationships, liver ENHO/adropin-related structures are dominated by transcripts expressed across metabolic tissues (skeletal muscle, adipose tissues, thyroid). Relationships between liver ENHO/adropin expression and skeletal muscle mitochondrial function were corroborated using liver-specific knockout mice. Within-liver ENHO/adropin transcriptional structures reflect lipoprotein metabolism (e.g., APOC1, p = 4.91 x 10−11; APOA1, p = 8.03 x 10−9), confirmed by correlations between plasma concentrations of adropin and indices of lipoprotein metabolism in MAPT samples. Moreover, statin treatment which increases hepatic cholesterol efflux, reduces plasma adropin levels. The ENHO gene contains retinoic acid receptor-related orphan receptor response elements (RORE), suggesting circadian control. Pan-organ transcriptional structures with liver ENHO/adropin or RORC overlap, reflecting the liver clock. Strong, local relationships between ENHO/adropin and circadian genes were also observed in most non-hepatic tissues. ENHO/adropin expression widely reflects activation of oxidative metabolic pathways and suppression of ribosomal functions and cell division. Finally, hippocampal ENHO/adropin expression correlates strongly with Alzheimer's disease risk genes identified by GWAS. In summary, activation of ENHO/adropin expression reflects cellular circadian and mitochondrial oxidative processes, but with inhibition of anabolic processes. Plasma adropin concentrations may thus reflect hepatic lipoprotein production and activation of metabolic stress responses across human tissues.
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spelling doaj-art-a519570e1e40420aaa37ecc5dd8a16852025-08-20T03:59:37ZengElsevierMolecular Metabolism2212-87782025-09-019910219610.1016/j.molmet.2025.102196Adropin expression reflects circadian, lipoprotein, and mitochondrial processes in human tissuesJoseph R. Stevens0Clemence Girardet1Mingqi Zhou2Farah Gamie3Geetika Aggarwal4Ryan P. McMillan5Matthew W. Hulver6Laurent O. Martinez7Marcel van der Brug8Bruno Vellas9Andrew D. Nguyen10Marcus M. Seldin11Andrew A. Butler12 MAPT Study Group13 Principal investigator14Bruno Vellas15 Coordination16Sophie Guyonnet17 Project leader18Isabelle Carrié19 CRA20Lauréane Brigitte21 Investigators22Catherine Faisant23Françoise Lala24Julien Delrieu25Hélène Villars26 Psychologists27Emeline Combrouze28Carole Badufle29Audrey Zueras30 Methodology, statistical analysis and data management31Sandrine Andrieu32Christelle Cantet33Christophe Morin34 Multidomain group35Gabor Abellan Van Kan36Charlotte Dupuy37Yves Rolland38Céline Caillaud39Pierre-Jean Ousset40Françoise Lala41 Co-Investigators in associated centres42Jean-François Dartigues43Isabelle Marcet44Fleur Delva45Alexandra Foubert46Sandrine Cerda47Marie-Noëlle Cuffi48Corinne Costes49Olivier Rouaud50Patrick Manckoundia51Valérie Quipourt52Sophie Marilier53Evelyne Franon54Lawrence Bories55Marie-Laure Pader56Marie-France Basset57Bruno Lapoujade58Valérie Faure59Michael Li Yung Tong60Christine Malick-Loiseau61Evelyne Cazaban-Campistron62Françoise Desclaux63Colette Blatge64Thierry Dantoine65Cécile Laubarie-Mouret66Isabelle Saulnier67Jean-Pierre Clément68Marie-Agnès Picat69Laurence Bernard-Bourzeix70Stéphanie Willebois71Iléana Désormais72Noëlle Cardinaud73Marc Bonnefoy74Pierre Livet75Pascale Rebaudet76Claire Gédéon77Catherine Burdet78Flavien Terracol79Alain Pesce80Stéphanie Roth81Sylvie Chaillou82Sandrine Louchart83Kristel Sudres84Nicolas Lebrun85Nadège Barro-Belaygues86Jacques Touchon87Karim Bennys88Audrey Gabelle89Aurélia Romano90Lynda Touati91Cécilia Marelli92Cécile Pays93Philippe Robert94Franck Le Duff95Claire Gervais96Sébastien Gonfrier97Yannick Gasnier98Serge Bordes99Danièle Begorre100Christian Carpuat101Khaled Khales102Jean-François Lefebvre103Samira Misbah El Idrissi104Pierre Skolil105Jean-Pierre Salles106 MRI group107Carole Dufouil108Stéphane Lehéricy109Marie Chupin110Jean-François Mangin111Ali Bouhayia112Michèle Allard113Frédéric Ricolfi114Dominique Dubois115Marie Paule Bonceour Martel116François Cotton117Alain Bonafé118Stéphane Chanalet119Françoise Hugon120Fabrice Bonneville121Christophe Cognard122François Chollet123 PET scans group124Pierre Payoux125Thierry Voisin126Julien Delrieu127Sophie Peiffer128Anne Hitzel129Michèle Allard130Michel Zanca131Jacques Monteil132Jacques Darcourt133 Medico-economics group134Laurent Molinier135Hélène Derumeaux136Nadège Costa137 Biological sample collection138Bertrand Perret139Claire Vinel140Sylvie Caspar-Bauguil141 Safety management142Pascale Olivier-Abbal143 IHU Open Science Group144Nicola Coley145Sandrine Andrieu146Christelle Cantet147Sophie Guyonnet148Department of Pharmacology and Physiology, Saint Louis University School of Medicine, St. Louis, Missouri, USADepartment of Pharmacology and Physiology, Saint Louis University School of Medicine, St. Louis, Missouri, USADepartment of Biological Chemistry and Center for Epigenetics and Metabolism, University of California, Irvine, CA, USADepartment of Biological Chemistry and Center for Epigenetics and Metabolism, University of California, Irvine, CA, USAInstitute for Translational Neuroscience, Saint Louis University, St. Louis, Missouri, USA; Division of Geriatric Medicine, Department of Internal Medicine, Saint Louis University School of Medicine, St. Louis, Missouri, USADepartment of Human Nutrition, Foods, and Exercise, Blacksburg, VA, USADepartment of Human Nutrition, Foods, and Exercise, Blacksburg, VA, USAInstitut des Maladies Métaboliques et Cardiovasculaires, I2MC, UMR1297, Inserm, Université de Toulouse, Toulouse, FranceAcuraStem, Pasadena, CA, USAGérontopôle de Toulouse, Institut du Vieillissement, Centre Hospitalo-Universitaire de Toulouse, 37 Allées Jules Guesdes, 31000, Toulouse, FranceInstitute for Translational Neuroscience, Saint Louis University, St. Louis, Missouri, USA; Division of Geriatric Medicine, Department of Internal Medicine, Saint Louis University School of Medicine, St. Louis, Missouri, USADepartment of Biological Chemistry and Center for Epigenetics and Metabolism, University of California, Irvine, CA, USAInstitute for Translational Neuroscience, Saint Louis University, St. Louis, Missouri, USA; Division of Geriatric Medicine, Department of Internal Medicine, Saint Louis University School of Medicine, St. Louis, Missouri, USA; Corresponding author.Toulouse; Bordeaux; Castres; Dijon; Foix; Lavaur; Limoges; Lyon; Monaco; Montauban; Montpellier; Nice; Tarbes; Bordeaux; Paris; Bordeaux; Dijon; Foix; Limoges; Lyon; Montpellier; Nice; Tarbes; Toulouse; Toulouse; Bordeaux; Montpellier; Limoges; Nice; Toulouse; ToulouseToulouse; Bordeaux; Castres; Dijon; Foix; Lavaur; Limoges; Lyon; Monaco; Montauban; Montpellier; Nice; Tarbes; Bordeaux; Paris; Bordeaux; Dijon; Foix; Limoges; Lyon; Montpellier; Nice; Tarbes; Toulouse; Toulouse; Bordeaux; Montpellier; Limoges; Nice; Toulouse; ToulouseToulouseToulouse; Bordeaux; Castres; Dijon; Foix; Lavaur; Limoges; Lyon; Monaco; Montauban; Montpellier; Nice; Tarbes; Bordeaux; Paris; Bordeaux; Dijon; Foix; Limoges; Lyon; Montpellier; Nice; Tarbes; Toulouse; Toulouse; Bordeaux; Montpellier; Limoges; Nice; Toulouse; ToulouseToulouse; Bordeaux; Castres; Dijon; 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Lyon; Montpellier; Nice; Tarbes; Toulouse; Toulouse; Bordeaux; Montpellier; Limoges; Nice; Toulouse; ToulouseToulouse; Bordeaux; Castres; Dijon; Foix; Lavaur; Limoges; Lyon; Monaco; Montauban; Montpellier; Nice; Tarbes; Bordeaux; Paris; Bordeaux; Dijon; Foix; Limoges; Lyon; Montpellier; Nice; Tarbes; Toulouse; Toulouse; Bordeaux; Montpellier; Limoges; Nice; Toulouse; ToulouseToulouse; Bordeaux; Castres; Dijon; Foix; Lavaur; Limoges; Lyon; Monaco; Montauban; Montpellier; Nice; Tarbes; Bordeaux; Paris; Bordeaux; Dijon; Foix; Limoges; Lyon; Montpellier; Nice; Tarbes; Toulouse; Toulouse; Bordeaux; Montpellier; Limoges; Nice; Toulouse; ToulouseToulouse; Bordeaux; Castres; Dijon; Foix; Lavaur; Limoges; Lyon; Monaco; Montauban; Montpellier; Nice; Tarbes; Bordeaux; Paris; Bordeaux; Dijon; Foix; Limoges; Lyon; Montpellier; Nice; Tarbes; Toulouse; Toulouse; Bordeaux; Montpellier; Limoges; Nice; Toulouse; ToulouseToulouse; Bordeaux; Castres; Dijon; Foix; Lavaur; Limoges; Lyon; Monaco; Montauban; Montpellier; Nice; Tarbes; Bordeaux; Paris; Bordeaux; Dijon; Foix; Limoges; Lyon; Montpellier; Nice; Tarbes; Toulouse; Toulouse; Bordeaux; Montpellier; Limoges; Nice; Toulouse; ToulouseToulouse; Bordeaux; Castres; Dijon; Foix; Lavaur; Limoges; Lyon; Monaco; Montauban; Montpellier; Nice; Tarbes; Bordeaux; Paris; Bordeaux; Dijon; Foix; Limoges; Lyon; Montpellier; Nice; Tarbes; Toulouse; Toulouse; Bordeaux; Montpellier; Limoges; Nice; Toulouse; ToulouseToulouse; Bordeaux; Castres; Dijon; Foix; Lavaur; Limoges; Lyon; Monaco; Montauban; Montpellier; Nice; Tarbes; Bordeaux; Paris; Bordeaux; Dijon; Foix; Limoges; Lyon; Montpellier; Nice; Tarbes; Toulouse; Toulouse; Bordeaux; Montpellier; Limoges; Nice; Toulouse; ToulouseToulouse; Bordeaux; Castres; Dijon; Foix; Lavaur; Limoges; Lyon; Monaco; Montauban; Montpellier; Nice; Tarbes; Bordeaux; Paris; Bordeaux; Dijon; Foix; Limoges; Lyon; Montpellier; Nice; Tarbes; Toulouse; Toulouse; Bordeaux; Montpellier; Limoges; Nice; Toulouse; ToulouseToulouse; Bordeaux; Castres; Dijon; Foix; Lavaur; Limoges; Lyon; Monaco; Montauban; Montpellier; Nice; Tarbes; Bordeaux; Paris; Bordeaux; Dijon; Foix; Limoges; Lyon; Montpellier; Nice; Tarbes; Toulouse; Toulouse; Bordeaux; Montpellier; Limoges; Nice; Toulouse; ToulouseToulouse; Bordeaux; Castres; Dijon; Foix; Lavaur; Limoges; Lyon; Monaco; Montauban; Montpellier; Nice; Tarbes; Bordeaux; Paris; Bordeaux; Dijon; Foix; Limoges; Lyon; Montpellier; Nice; Tarbes; Toulouse; Toulouse; Bordeaux; Montpellier; Limoges; Nice; Toulouse; ToulouseToulouse; Bordeaux; Castres; Dijon; Foix; Lavaur; Limoges; Lyon; Monaco; Montauban; Montpellier; Nice; Tarbes; Bordeaux; Paris; Bordeaux; Dijon; Foix; Limoges; Lyon; Montpellier; Nice; Tarbes; Toulouse; Toulouse; Bordeaux; Montpellier; Limoges; Nice; Toulouse; ToulouseToulouse; Bordeaux; Castres; Dijon; Foix; Lavaur; Limoges; Lyon; Monaco; Montauban; Montpellier; Nice; Tarbes; Bordeaux; Paris; Bordeaux; Dijon; Foix; Limoges; Lyon; Montpellier; Nice; Tarbes; Toulouse; Toulouse; Bordeaux; Montpellier; Limoges; Nice; Toulouse; ToulouseToulouse; Bordeaux; Castres; Dijon; Foix; Lavaur; Limoges; Lyon; Monaco; Montauban; Montpellier; Nice; Tarbes; Bordeaux; Paris; Bordeaux; Dijon; Foix; Limoges; Lyon; Montpellier; Nice; Tarbes; Toulouse; Toulouse; Bordeaux; Montpellier; Limoges; Nice; Toulouse; ToulouseToulouse; Bordeaux; Castres; Dijon; Foix; Lavaur; Limoges; Lyon; Monaco; Montauban; Montpellier; Nice; Tarbes; Bordeaux; Paris; Bordeaux; Dijon; Foix; Limoges; Lyon; Montpellier; Nice; Tarbes; Toulouse; Toulouse; Bordeaux; Montpellier; Limoges; Nice; Toulouse; ToulouseToulouse; Bordeaux; Castres; Dijon; Foix; Lavaur; Limoges; Lyon; Monaco; Montauban; Montpellier; Nice; Tarbes; Bordeaux; Paris; Bordeaux; Dijon; Foix; Limoges; Lyon; Montpellier; Nice; Tarbes; Toulouse; Toulouse; Bordeaux; Montpellier; Limoges; Nice; Toulouse; ToulouseToulouse; Bordeaux; Castres; Dijon; Foix; Lavaur; Limoges; Lyon; Monaco; Montauban; Montpellier; Nice; Tarbes; Bordeaux; Paris; 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Bordeaux; Castres; Dijon; Foix; Lavaur; Limoges; Lyon; Monaco; Montauban; Montpellier; Nice; Tarbes; Bordeaux; Paris; Bordeaux; Dijon; Foix; Limoges; Lyon; Montpellier; Nice; Tarbes; Toulouse; Toulouse; Bordeaux; Montpellier; Limoges; Nice; Toulouse; ToulouseToulouseToulouseToulouseToulouse; Bordeaux; Castres; Dijon; Foix; Lavaur; Limoges; Lyon; Monaco; Montauban; Montpellier; Nice; Tarbes; Bordeaux; Paris; Bordeaux; Dijon; Foix; Limoges; Lyon; Montpellier; Nice; Tarbes; Toulouse; Toulouse; Bordeaux; Montpellier; Limoges; Nice; Toulouse; ToulouseToulouse; Bordeaux; Castres; Dijon; Foix; Lavaur; Limoges; Lyon; Monaco; Montauban; Montpellier; Nice; Tarbes; Bordeaux; Paris; Bordeaux; Dijon; Foix; Limoges; Lyon; Montpellier; Nice; Tarbes; Toulouse; Toulouse; Bordeaux; Montpellier; Limoges; Nice; Toulouse; ToulouseToulouse; Bordeaux; Castres; Dijon; Foix; Lavaur; Limoges; Lyon; Monaco; Montauban; Montpellier; Nice; Tarbes; Bordeaux; Paris; Bordeaux; Dijon; Foix; Limoges; Lyon; Montpellier; Nice; Tarbes; Toulouse; Toulouse; Bordeaux; Montpellier; Limoges; Nice; Toulouse; ToulouseToulouse; Bordeaux; Castres; Dijon; Foix; Lavaur; Limoges; Lyon; Monaco; Montauban; Montpellier; Nice; Tarbes; Bordeaux; Paris; Bordeaux; Dijon; Foix; Limoges; Lyon; Montpellier; Nice; Tarbes; Toulouse; Toulouse; Bordeaux; Montpellier; Limoges; Nice; Toulouse; ToulouseToulouse; Bordeaux; Castres; Dijon; Foix; Lavaur; Limoges; Lyon; Monaco; Montauban; Montpellier; Nice; Tarbes; Bordeaux; Paris; Bordeaux; Dijon; Foix; Limoges; Lyon; Montpellier; Nice; Tarbes; Toulouse; Toulouse; Bordeaux; Montpellier; Limoges; Nice; Toulouse; ToulouseToulouse; Bordeaux; Castres; Dijon; Foix; Lavaur; Limoges; Lyon; Monaco; Montauban; Montpellier; Nice; Tarbes; Bordeaux; Paris; Bordeaux; Dijon; Foix; Limoges; Lyon; Montpellier; Nice; Tarbes; Toulouse; Toulouse; Bordeaux; Montpellier; Limoges; Nice; Toulouse; ToulouseToulouse; Bordeaux; Castres; Dijon; Foix; Lavaur; Limoges; Lyon; Monaco; Montauban; Montpellier; Nice; Tarbes; Bordeaux; Paris; Bordeaux; Dijon; Foix; Limoges; Lyon; Montpellier; Nice; Tarbes; Toulouse; Toulouse; Bordeaux; Montpellier; Limoges; Nice; Toulouse; ToulouseThe clinical significance of interindividual variation in circulating adropin levels is unclear. To better understand adropin biology at the whole-body level, we surveyed transcriptional structures co-regulated with the Energy Homeostasis Associated (ENHO) gene encoding adropin across human tissues using Gene-Derived Correlations Across Tissues (GD-CAT). ENHO/adropin-related transcriptional structures with >1000 genes meeting the selection threshold (q < 0.001) occurred in 11/20 tissues. While most reflect local relationships, liver ENHO/adropin-related structures are dominated by transcripts expressed across metabolic tissues (skeletal muscle, adipose tissues, thyroid). Relationships between liver ENHO/adropin expression and skeletal muscle mitochondrial function were corroborated using liver-specific knockout mice. Within-liver ENHO/adropin transcriptional structures reflect lipoprotein metabolism (e.g., APOC1, p = 4.91 x 10−11; APOA1, p = 8.03 x 10−9), confirmed by correlations between plasma concentrations of adropin and indices of lipoprotein metabolism in MAPT samples. Moreover, statin treatment which increases hepatic cholesterol efflux, reduces plasma adropin levels. The ENHO gene contains retinoic acid receptor-related orphan receptor response elements (RORE), suggesting circadian control. Pan-organ transcriptional structures with liver ENHO/adropin or RORC overlap, reflecting the liver clock. Strong, local relationships between ENHO/adropin and circadian genes were also observed in most non-hepatic tissues. ENHO/adropin expression widely reflects activation of oxidative metabolic pathways and suppression of ribosomal functions and cell division. Finally, hippocampal ENHO/adropin expression correlates strongly with Alzheimer's disease risk genes identified by GWAS. In summary, activation of ENHO/adropin expression reflects cellular circadian and mitochondrial oxidative processes, but with inhibition of anabolic processes. Plasma adropin concentrations may thus reflect hepatic lipoprotein production and activation of metabolic stress responses across human tissues.http://www.sciencedirect.com/science/article/pii/S2212877825001036
spellingShingle Joseph R. Stevens
Clemence Girardet
Mingqi Zhou
Farah Gamie
Geetika Aggarwal
Ryan P. McMillan
Matthew W. Hulver
Laurent O. Martinez
Marcel van der Brug
Bruno Vellas
Andrew D. Nguyen
Marcus M. Seldin
Andrew A. Butler
MAPT Study Group
Principal investigator
Bruno Vellas
Coordination
Sophie Guyonnet
Project leader
Isabelle Carrié
CRA
Lauréane Brigitte
Investigators
Catherine Faisant
Françoise Lala
Julien Delrieu
Hélène Villars
Psychologists
Emeline Combrouze
Carole Badufle
Audrey Zueras
Methodology, statistical analysis and data management
Sandrine Andrieu
Christelle Cantet
Christophe Morin
Multidomain group
Gabor Abellan Van Kan
Charlotte Dupuy
Yves Rolland
Céline Caillaud
Pierre-Jean Ousset
Françoise Lala
Co-Investigators in associated centres
Jean-François Dartigues
Isabelle Marcet
Fleur Delva
Alexandra Foubert
Sandrine Cerda
Marie-Noëlle Cuffi
Corinne Costes
Olivier Rouaud
Patrick Manckoundia
Valérie Quipourt
Sophie Marilier
Evelyne Franon
Lawrence Bories
Marie-Laure Pader
Marie-France Basset
Bruno Lapoujade
Valérie Faure
Michael Li Yung Tong
Christine Malick-Loiseau
Evelyne Cazaban-Campistron
Françoise Desclaux
Colette Blatge
Thierry Dantoine
Cécile Laubarie-Mouret
Isabelle Saulnier
Jean-Pierre Clément
Marie-Agnès Picat
Laurence Bernard-Bourzeix
Stéphanie Willebois
Iléana Désormais
Noëlle Cardinaud
Marc Bonnefoy
Pierre Livet
Pascale Rebaudet
Claire Gédéon
Catherine Burdet
Flavien Terracol
Alain Pesce
Stéphanie Roth
Sylvie Chaillou
Sandrine Louchart
Kristel Sudres
Nicolas Lebrun
Nadège Barro-Belaygues
Jacques Touchon
Karim Bennys
Audrey Gabelle
Aurélia Romano
Lynda Touati
Cécilia Marelli
Cécile Pays
Philippe Robert
Franck Le Duff
Claire Gervais
Sébastien Gonfrier
Yannick Gasnier
Serge Bordes
Danièle Begorre
Christian Carpuat
Khaled Khales
Jean-François Lefebvre
Samira Misbah El Idrissi
Pierre Skolil
Jean-Pierre Salles
MRI group
Carole Dufouil
Stéphane Lehéricy
Marie Chupin
Jean-François Mangin
Ali Bouhayia
Michèle Allard
Frédéric Ricolfi
Dominique Dubois
Marie Paule Bonceour Martel
François Cotton
Alain Bonafé
Stéphane Chanalet
Françoise Hugon
Fabrice Bonneville
Christophe Cognard
François Chollet
PET scans group
Pierre Payoux
Thierry Voisin
Julien Delrieu
Sophie Peiffer
Anne Hitzel
Michèle Allard
Michel Zanca
Jacques Monteil
Jacques Darcourt
Medico-economics group
Laurent Molinier
Hélène Derumeaux
Nadège Costa
Biological sample collection
Bertrand Perret
Claire Vinel
Sylvie Caspar-Bauguil
Safety management
Pascale Olivier-Abbal
IHU Open Science Group
Nicola Coley
Sandrine Andrieu
Christelle Cantet
Sophie Guyonnet
Adropin expression reflects circadian, lipoprotein, and mitochondrial processes in human tissues
Molecular Metabolism
title Adropin expression reflects circadian, lipoprotein, and mitochondrial processes in human tissues
title_full Adropin expression reflects circadian, lipoprotein, and mitochondrial processes in human tissues
title_fullStr Adropin expression reflects circadian, lipoprotein, and mitochondrial processes in human tissues
title_full_unstemmed Adropin expression reflects circadian, lipoprotein, and mitochondrial processes in human tissues
title_short Adropin expression reflects circadian, lipoprotein, and mitochondrial processes in human tissues
title_sort adropin expression reflects circadian lipoprotein and mitochondrial processes in human tissues
url http://www.sciencedirect.com/science/article/pii/S2212877825001036
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