Low Carbohydrate Availability in Energy Balance Alters Bone Turnover and Muscle Proteomic Response With Limited Endocrine Disruption

Mosquera-Lopez, E ORCID: 0000-0002-0505-0352, Taylor, HL ORCID: 0000-0002-6925-6982, Nishimura, Y ORCID: 0000-0001-8225-7675, Langan-Evans, C ORCID: 0000-0003-1120-6592, Shepherd, SO ORCID: 0000-0001-6292-1356, Strauss, JA ORCID: 0000-0001-7175-2494, Morton, JP ORCID: 0000-0003-2776-2542, Burniston, JG ORCID: 0000-0001-7303-9318 and Areta, JL ORCID: 0000-0001-6918-1223 (2026) Low Carbohydrate Availability in Energy Balance Alters Bone Turnover and Muscle Proteomic Response With Limited Endocrine Disruption. The FASEB Journal, 40 (17). ISSN 0892-6638

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Abstract

Training with low carbohydrate availability (LCA) has been proposed as an independent determinant of physiological perturbations commonly attributed to low energy availability (LEA) and to increase skeletal muscle oxidative machinery, yet the effects of LCA in isolation from LEA remain unclear. We examined whether short-term carbohydrate restriction under energy balance alters endocrine and metabolic markers associated with LEA and skeletal muscle proteomic response. In a randomized crossover design, eight trained males completed 4 days of either a low-carbohydrate high-fat diet (LOW; 12% carbohydrate, 69% fat, 19% protein) or a normal-carbohydrate diet (NORM; 62% carbohydrate, 19% fat, 19% protein), while undertaking daily cycloergometer exercise (15 kcal kg FFM−1 day−1) and maintaining energy availability at 45 kcal kg FFM−1 day−1. LOW induced a clear metabolic shift consistent with LCA, evidenced by elevated circulating free fatty acids, glycerol and β-hydroxybutyrate, in fasting conditions and fat oxidation at rest and during exercise, alongside reduced exercise glucose concentrations. Despite these responses, LOW did not alter insulin, testosterone, triiodothyronine, leptin, hepcidin, or P1NP. In contrast, β-CTX increased and IGF-1 decreased relative to NORM. Muscle glycogen concentration decreased only in LOW (40% ± 14%). Proteomic analysis identified 671 proteins; 57 differentially expressed in LOW relative to NORM were limited to fatty acid metabolism pathways and suppression of ribosomal, sarcomeric, and extracellular matrix proteins. These findings indicate that isolated LCA exerts limited endocrine disruption but may selectively compromise bone turnover and muscle anabolic response, suggesting that without acute LEA, LCA has limited influence on muscle oxidative phenotype.

Item Type:	Article
Uncontrolled Keywords:	dietary periodisation; energy deficit; low-carbohydrate high-fat diet; muscle proteomics; Muscle, Skeletal; Humans; Cross-Over Studies; Proteomics; Energy Metabolism; Male; Diet, Carbohydrate-Restricted; dietary periodisation; energy deficit; low‐carbohydrate high‐fat diet; muscle proteomics; Male; Energy Metabolism; Muscle, Skeletal; Humans; Proteomics; Diet, Carbohydrate-Restricted; Cross-Over Studies; 32 Biomedical and Clinical Sciences; 3210 Nutrition and Dietetics; Nutrition; Physical Activity; Clinical Research; Prevention; Obesity; Musculoskeletal; 3 Good Health and Well Being; Male; Energy Metabolism; Muscle, Skeletal; Humans; Proteomics; Diet, Carbohydrate-Restricted; Cross-Over Studies; 0601 Biochemistry and Cell Biology; 0606 Physiology; 1116 Medical Physiology; Biochemistry & Molecular Biology; 3101 Biochemistry and cell biology; 3208 Medical physiology
Subjects:	T Technology > TX Home economics > TX341 Nutrition. Foods and food supply R Medicine > RC Internal medicine
Divisions:	Sport and Exercise Sciences
Publisher:	Wiley
Date of acceptance:	10 August 2026
Date of first compliant Open Access:	29 October 2026
Date Deposited:	29 Oct 2026 10:22
Last Modified:	29 Oct 2026 10:23
DOI or ID number:	10.1096/fj.202602531R
URI:	https://researchonline.ljmu.ac.uk/id/eprint/29760

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