Endocrine, Metabolic, and Skeletal Muscle Proteomic Responses During Energy Deficit With Concomitant Aerobic Exercise in Humans

Nishimura, Y ORCID: 0000-0001-8225-7675, Langan‐Evans, C ORCID: 0000-0003-1120-6592, Taylor, HL, Foo, WL ORCID: 0009-0001-8702-9898, Morton, JP ORCID: 0000-0003-2776-2542, Shepherd, S, Strauss, JA ORCID: 0000-0001-7175-2494, Burniston, JG ORCID: 0000-0001-7303-9318 and Areta, JL ORCID: 0000-0001-6918-1223 (2025) Endocrine, Metabolic, and Skeletal Muscle Proteomic Responses During Energy Deficit With Concomitant Aerobic Exercise in Humans. The FASEB Journal, 39 (21). pp. 1-20. ISSN 0892-6638

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Abstract

Energy deficit is a potent physiological stressor that has shaped human evolution and can improve lifespan and healthspan in a wide range of species. Preserving locomotive capacity was likely essential for survival during the human hunter-gatherer period but surprisingly little is known about the molecular effects of energy deficit on human skeletal muscle, which is a key tissue for locomotion and metabolic health. Here we show that after a 5-day 78% reduction in energy availability with concomitant aerobic exercise in healthy men there was a profound modulation of skeletal muscle phenotype alongside increases in fat oxidation at rest and during exercise and a 2.1 ± 0.8 kg loss of fat free mass and 0.8 ± 0.6 kg of fat mass. We used stable isotope (D2O) labelling and peptide mass spectrometry to investigate the abundance and turnover rates of individual proteins. Abundance (1469 proteins) and synthesis rate (736 proteins) data discovered a shift toward a more oxidative phenotype and reorganization of cytoskeleton and extracellular matrix structure during energy deficit. Mitochondrial components: TCA, electron transport chain and beta-oxidation, were prominently represented amongst proteins that increased in abundance and synthesis rate, as well as proteins related to mitochondrial proteostasis, remodeling and quality-control such as BDH1 and LONP1. Changes in muscle metabolic pathways occurred alongside a reduction in extracellular matrix proteins, which may counteract the age-related muscle fibrosis. Our results suggest that muscle metabolic pathways are not only preserved but positively affected during periods of concomitant low energy availability and exercise.

Item Type:	Article
Uncontrolled Keywords:	0601 Biochemistry and Cell Biology; 0606 Physiology; 1116 Medical Physiology; Biochemistry & Molecular Biology; 3101 Biochemistry and cell biology; 3208 Medical physiology
Subjects:	R Medicine > RC Internal medicine > RC1200 Sports Medicine
Divisions:	Sport and Exercise Sciences
Publisher:	Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology
Date of acceptance:	10 October 2025
Date of first compliant Open Access:	4 November 2025
Date Deposited:	04 Nov 2025 11:24
Last Modified:	04 Nov 2025 11:45
DOI or ID number:	10.1096/fj.202502384rr
URI:	https://researchonline.ljmu.ac.uk/id/eprint/27480

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