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

Abstract Aims To 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 Methods In 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 (VO 2 peak), and plasma cytokeratin‐18 (CK18) M65, among others. Results In 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 ( r s ≥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 VO 2 peak was increased ( p ≤ 0.030). ΔVO 2 peak was inversely associated with Δhepatic SI ( r = −0.433) and positively associated with Δhepatic UI and Δhepatic PUI ( r ≥ 0.433). Conclusions Impaired 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.