Dataset Information

D2O proteome dynamics in response to energy deficit

ABSTRACT: Energy deficit has shaped human evolution, and represents a potent physiological stressor associated with improvements in lifespan and healthspan in several species. Preserving locomotive capacity has likely been essential for food procurement and survival from starvation during the hunter-gatherer period. However, we have very limited understanding of the effect of energy deficit on skeletal muscle, a key tissue for locomotion and metabolic health. Here we show that a 5-day 78% reduction in energy availability with concomitant exercise in healthy men leads to 2.1 ±0.8 kg loss of fat free mass and 0.8 ±0.6 kg of fat mass; increases fat oxidation at rest and during exercise, and induces metabolic and endocrine shifts associated to energy preservation, concomitant with a profound modulation of skeletal muscle phenotype. We used stable isotope (deuterium oxide) labelling and peptide mass spectrometry to investigate the abundance and turnover rates of individual proteins. Abundance (1469 proteins) and absolute synthesis rates (736 proteins) show a shift towards an oxidative phenotype, and cytoskeleton and extracellular matrix remodelling during energy deficit compared to energy balance. Mitochondrial components: TCA, electron transport chain and beta-oxidation, are prominently represented amongst the proteins that increase in abundance and synthesis rate, as well as proteins associated to mitochondrial proteostasis, remodelling and quality-control such as BDH1 and LONP1. The changes in muscle metabolic pathways occurred alongside a reduction in extracellular matrix proteins, which may oppose the age-related increases in fibrotic tissue in muscle. Our results suggest that muscle metabolic pathways are not only preserved but positively affected during periods of low energy availability and physical demands.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Skeletal Muscle

SUBMITTER: Yusuke Nishimura

LAB HEAD: Jatin Burniston

PROVIDER: PXD061267 | Pride | 2025-11-04

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	Margulis_experimental.design.xlsx	Xlsx
	Margulis_myofibrillar.MSMS.mgf	Mgf
	Margulis_myofibrillar.mzid	Mzid
	Margulis_myofibrillar_1.raw	Raw
	Margulis_myofibrillar_10.raw	Raw

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Publications

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

Nishimura Yusuke Y Langan-Evans Carl C Taylor Harry L HL Foo Wee L WL Morton James P JP Shepherd Sam S Strauss Juliette A JA Burniston Jatin G JG Areta José L JL

FASEB journal : official publication of the Federation of American Societies for Experimental Biology 20251101 21

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 concomi ...[more]

PMID: 41182317

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