Conserved multi-tissue transcriptomic adaptations to exercise training in humans and mice

Timothy M Moore; Sindre Lee; Thomas Olsen; Marco Morselli; Alexander R Strumwasser; Amanda J Lin; Zhenqi Zhou; Aaron Abrishami; Steven M Garcia; Jennifer Bribiesca; Kevin Cory; Kate Whitney; Theodore Ho; Timothy Ho; Joseph L Lee; Daniel H Rucker; Christina Q A Nguyen; Akshay T S Anand; Aidan Yackly; Lorna Q Mendoza; Brayden K Leyva; Claudia Aliman; Daniel J Artiga; Yonghong Meng; Sarada Charugundla; Calvin Pan; Vida Jedian; Marcus M Seldin; In Sook Ahn; Graciel Diamante; Montgomery Blencowe; Xia Yang; Etienne Mouisel; Matteo Pellegrini; Lorraine P Turcotte; Kåre I Birkeland; Frode Norheim; Christian A Drevon; Aldons J Lusis; Andrea L Hevener

doi:10.1016/j.celrep.2023.112499

Conserved multi-tissue transcriptomic adaptations to exercise training in humans and mice

Cell Rep. 2023 May 30;42(5):112499. doi: 10.1016/j.celrep.2023.112499. Epub 2023 May 12.

Authors

Timothy M Moore¹, Sindre Lee², Thomas Olsen³, Marco Morselli⁴, Alexander R Strumwasser⁵, Amanda J Lin⁶, Zhenqi Zhou⁵, Aaron Abrishami², Steven M Garcia⁵, Jennifer Bribiesca⁵, Kevin Cory⁵, Kate Whitney⁵, Theodore Ho⁵, Timothy Ho⁵, Joseph L Lee⁵, Daniel H Rucker⁵, Christina Q A Nguyen⁵, Akshay T S Anand⁵, Aidan Yackly⁵, Lorna Q Mendoza⁵, Brayden K Leyva⁵, Claudia Aliman², Daniel J Artiga⁵, Yonghong Meng⁷, Sarada Charugundla⁷, Calvin Pan⁷, Vida Jedian⁷, Marcus M Seldin⁸, In Sook Ahn⁹, Graciel Diamante⁹, Montgomery Blencowe¹⁰, Xia Yang¹¹, Etienne Mouisel¹², Matteo Pellegrini¹³, Lorraine P Turcotte¹⁴, Kåre I Birkeland², Frode Norheim¹⁵, Christian A Drevon³, Aldons J Lusis¹⁶, Andrea L Hevener¹⁷

Affiliations

¹ Division of Cardiology, Diabetes, and Hypertension, Department of Medicine, David Geffen School of Medicine University of California, Los Angeles, Los Angeles, CA, USA; Division of Endocrinology, Diabetes, and Hypertension, Department of Medicine, David Geffen School of Medicine University of California, Los Angeles, Los Angeles, CA, USA.
² Department of Transplantation, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
³ Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway.
⁴ Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, CA, USA; UCLA-DOE Institute for Genomics and Proteomics, University of California Los Angeles, Los Angeles, CA, USA; Institute for Quantitative and Computational Biosciences - The Collaboratory, University of California, Los Angeles, Los Angeles, CA, USA.
⁵ Division of Endocrinology, Diabetes, and Hypertension, Department of Medicine, David Geffen School of Medicine University of California, Los Angeles, Los Angeles, CA, USA.
⁶ Division of Endocrinology, Diabetes, and Hypertension, Department of Medicine, David Geffen School of Medicine University of California, Los Angeles, Los Angeles, CA, USA; Department of Chemical and Systems Biology, Stanford School of Medicine, Stanford, CA, USA.
⁷ Division of Cardiology, Diabetes, and Hypertension, Department of Medicine, David Geffen School of Medicine University of California, Los Angeles, Los Angeles, CA, USA.
⁸ Division of Cardiology, Diabetes, and Hypertension, Department of Medicine, David Geffen School of Medicine University of California, Los Angeles, Los Angeles, CA, USA; Department of Biological Chemistry and Center for Epigenetics and Metabolism, University of California, Irvine, Irvine, CA, USA.
⁹ Molecular, Cellular, and Integrative Physiology Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA, USA.
¹⁰ Molecular, Cellular, and Integrative Physiology Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA, USA; Institute for Quantitative and Computational Biosciences, University of California, Los Angeles, Los Angeles, CA, USA.
¹¹ Molecular, Cellular, and Integrative Physiology Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA, USA; Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA, USA; Institute for Quantitative and Computational Biosciences, University of California, Los Angeles, Los Angeles, CA, USA.
¹² Institute of Metabolic and Cardiovascular Diseases, UMR1297 Inserm, Paul Sabatier University, Toulouse, France.
¹³ UCLA-DOE Institute for Genomics and Proteomics, University of California Los Angeles, Los Angeles, CA, USA.
¹⁴ Department of Biological Sciences, Dana & David Dornsife College of Letters, Arts, and Sciences, University of Southern California, Los Angeles, CA, USA.
¹⁵ Division of Cardiology, Diabetes, and Hypertension, Department of Medicine, David Geffen School of Medicine University of California, Los Angeles, Los Angeles, CA, USA; Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway.
¹⁶ Division of Cardiology, Diabetes, and Hypertension, Department of Medicine, David Geffen School of Medicine University of California, Los Angeles, Los Angeles, CA, USA; Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA, USA; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
¹⁷ Division of Endocrinology, Diabetes, and Hypertension, Department of Medicine, David Geffen School of Medicine University of California, Los Angeles, Los Angeles, CA, USA; Iris Cantor-UCLA Women's Health Research Center, Los Angeles, CA, USA; Veterans Administration Greater Los Angeles Healthcare System, Geriatric Research Education and Clinical Center (GRECC), Los Angeles, CA, USA. Electronic address: ahevener@mednet.ucla.edu.

Abstract

Physical activity is associated with beneficial adaptations in human and rodent metabolism. We studied over 50 complex traits before and after exercise intervention in middle-aged men and a panel of 100 diverse strains of female mice. Candidate gene analyses in three brain regions, muscle, liver, heart, and adipose tissue of mice indicate genetic drivers of clinically relevant traits, including volitional exercise volume, muscle metabolism, adiposity, and hepatic lipids. Although ∼33% of genes differentially expressed in skeletal muscle following the exercise intervention are similar in mice and humans independent of BMI, responsiveness of adipose tissue to exercise-stimulated weight loss appears controlled by species and underlying genotype. We leveraged genetic diversity to generate prediction models of metabolic trait responsiveness to volitional activity offering a framework for advancing personalized exercise prescription. The human and mouse data are publicly available via a user-friendly Web-based application to enhance data mining and hypothesis development.

Keywords: CP: Metabolism; CP: Molecular biology; HMDP; exercise; genetics; multi-omics; physical activity; physiology; systems biology.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Acclimatization
Adaptation, Physiological*
Adipose Tissue / metabolism
Animals
Female
Humans
Male
Mice
Middle Aged
Muscle, Skeletal / metabolism
Obesity / metabolism
Transcriptome* / genetics

Abstract

Publication types

MeSH terms

Grants and funding