Greater hepatic lipid saturation is associated with impaired glycaemic regulation in men with metabolic dysfunction‐associated steatotic liver disease but is not altered by 6 weeks of exercise training

Author:

Willis Scott A.12,Malaikah Sundus123,Bawden Stephen J.45,Sherry Aron P.126,Sargeant Jack A.27ORCID,Coull Nicole A.28,Bradley Christopher R.45,Rowlands Alex28,Naim Iyad45,Ennequin Gaël9,Yates Thomas28,Waheed Ghazala28ORCID,Gowland Penny45,Stensel David J.1210,Webb David R.28ORCID,Davies Melanie J.28ORCID,Aithal Guruprasad P.511,King James A.12ORCID

Affiliation:

1. National Centre for Sport and Exercise Medicine School of Sport, Exercise and Health Sciences, Loughborough University Loughborough UK

2. NIHR Leicester Biomedical Research Centre University Hospitals of Leicester NHS Trust and the University of Leicester Leicester UK

3. Clinical Nutrition Department, Faculty of Applied Medical Sciences King Abdulaziz University Jeddah Saudi Arabia

4. Sir Peter Mansfield Imaging Centre University of Nottingham Nottingham UK

5. NIHR Nottingham Biomedical Research Centre Nottingham University Hospitals NHS Trust and the University of Nottingham Nottingham UK

6. Lifespan and Population Health, School of Medicine University of Nottingham Nottingham UK

7. Leicester Diabetes Centre University Hospitals of Leicester NHS Trust Leicester UK

8. Diabetes Research Centre University of Leicester Leicester UK

9. Laboratory of Metabolic Adaptations to Exercise Under Physiological and Pathological Conditions (AME2P) Université of Clermont Auvergne Clermont‐Ferrand France

10. Faculty of Sport Sciences Waseda University Tokorozawa Japan

11. Nottingham Digestive Diseases Centre, Translational Medical Sciences, School of Medicine University of Nottingham Nottingham UK

Abstract

AbstractAimsTo examine the impact of impaired glycaemic regulation (IGR) and exercise training on hepatic lipid composition in men with metabolic dysfunction‐associated steatotic liver disease (MASLD).Materials and MethodsIn Part A (cross‐sectional design), 40 men with MASLD (liver proton density fat fraction [PDFF] ≥5.56%) were recruited to one of two groups: (1) normal glycaemic regulation (NGR) group (glycated haemoglobin [HbA1c] < 42 mmol∙mol−1 [<6.0%]; n = 14) or (2) IGR group (HbA1c ≥ 42 mmol∙mol−1 [≥6.0%]; n = 26). In Part B (randomized controlled trial design), participants in the IGR group were randomized to one of two 6‐week interventions: (1) exercise training (EX; 70%–75% maximum heart rate; four sessions/week; n = 13) or (2) non‐exercise control (CON; n = 13). Saturated (SI; primary outcome), unsaturated (UI) and polyunsaturated (PUI) hepatic lipid indices were determined using proton magnetic resonance spectroscopy. Additional secondary outcomes included liver PDFF, HbA1c, fasting plasma glucose (FPG), homeostatic model assessment of insulin resistance (HOMA‐IR), peak oxygen uptake (VO2 peak), and plasma cytokeratin‐18 (CK18) M65, among others.ResultsIn Part A, hepatic SI was higher and hepatic UI was lower in the IGR versus the NGR group (p = 0.038), and this hepatic lipid profile was associated with higher HbA1c levels, FPG levels, HOMA‐IR and plasma CK18 M65 levels (rs ≥0.320). In Part B, hepatic lipid composition and liver PDFF were unchanged after EX versus CON (p ≥ 0.257), while FPG was reduced and VO2 peak was increased (p ≤ 0.030). ΔVO2 peak was inversely associated with Δhepatic SI (r = −0.433) and positively associated with Δhepatic UI and Δhepatic PUI (r ≥ 0.433).ConclusionsImpaired glycaemic regulation in MASLD is characterized by greater hepatic lipid saturation; however, this composition is not altered by 6 weeks of moderate‐intensity exercise training.

Funder

Diabetes UK

NIHR Leicester Biomedical Research Centre

NIHR Nottingham Biomedical Research Centre

Publisher

Wiley

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