Divergent remodeling of the skeletal muscle metabolome over 24 h between young, healthy men and older, metabolically compromised men

Jan-Frieder Harmsen; Michel van Weeghel; Rex Parsons; Georges E Janssens; Jakob Wefers; Dirk van Moorsel; Jan Hansen; Joris Hoeks; Matthijs K C Hesselink; Riekelt H Houtkooper; Patrick Schrauwen

doi:10.1016/j.celrep.2022.111786

Divergent remodeling of the skeletal muscle metabolome over 24 h between young, healthy men and older, metabolically compromised men

Cell Rep. 2022 Dec 13;41(11):111786. doi: 10.1016/j.celrep.2022.111786.

Affiliations

¹ Department of Nutrition and Movement Sciences, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, 6200 MD Maastricht, the Netherlands.
² Laboratory Genetic Metabolic Diseases, Amsterdam Gastroenterology, Endocrinology, and Metabolism, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands; Core Facility Metabolomics, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
³ Australian Centre for Health Services Innovation and Centre for Healthcare Transformation, School of Public Health and Social Work, Faculty of Health, Queensland University of Technology, Kelvin Grove, QLD, Australia.
⁴ Laboratory Genetic Metabolic Diseases, Amsterdam Gastroenterology, Endocrinology, and Metabolism, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.
⁵ Division of Endocrinology, Department of Internal Medicine, Maastricht University Medical Center, 6200 MD Maastricht, the Netherlands.
⁶ Laboratory Genetic Metabolic Diseases, Amsterdam Gastroenterology, Endocrinology, and Metabolism, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands. Electronic address: [email protected].
⁷ Department of Nutrition and Movement Sciences, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, 6200 MD Maastricht, the Netherlands. Electronic address: [email protected].

PMID: 36516749
DOI: 10.1016/j.celrep.2022.111786

Abstract

24 h whole-body substrate metabolism and the circadian clock within skeletal muscle are both compromised upon metabolic disease in humans. Here, we assessed the 24 h muscle metabolome by serial muscle sampling performed under 24 h real-life conditions in young, healthy (YH) men versus older, metabolically compromised (OMC) men. We find that metabolites associated with the initial steps of glycolysis and hexosamine biosynthesis are higher in OMC men around the clock, whereas metabolites associated with glutamine-alpha-ketoglutarate, ketone, and redox metabolism are lower in OMC men. The night period shows the largest number of differently expressed metabolites. Both groups demonstrate 24 h rhythmicity in half of the metabolome, but rhythmic metabolites only partially overlap. Specific metabolites are only rhythmic in YH men (adenosine), phase shifted in OMC men (cis-aconitate, flavin adenine dinucleotide [FAD], and uridine diphosphate [UDP]), or have a reduced 24 h amplitude in OMC men (hydroxybutyrate and hippuric acid). Our data highlight the plasticity of the skeletal muscle metabolome over 24 h and large divergence across the metabolic health spectrum.

Keywords: CP: Metabolism; FAD; PGK1; adenosine; circadian rhythm; glycolysis; hexosamine; hydroxybutyrate; insulin resistance; metabolomics; misalignment.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Circadian Clocks*
Circadian Rhythm / physiology
Glycolysis
Humans
Male
Metabolome*
Muscle, Skeletal / metabolism
Oxidation-Reduction