Exercise increases myocardial free fatty acid oxidation in subjects with metabolic dysfunction-associated fatty liver disease

Jeyanthini Risikesan, Sara Heebøll, Indumathi Kumarathas, Kristian L. Funck, Esben Søndergaard, Rakel F. Johansen, Steffen Ringgaard, Lars P. Tolbod, Mogens Johannsen, Helle L. Kanstrup, Henning Grønbæk, Jan Frystyk, Lars C. Gormsen, Søren Nielsen*


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Background and aims: Metabolic dysfunction-associated fatty liver disease (MAFLD) is associated with dyslipidemia and may promote cardiac lipotoxicity. Myocardial free fatty acids (FFA) oxidation (MOFFA) is normal in pre-diabetes, but reduced in heart failure. We hypothesized that during exercise MOFFA, very low-density lipoprotein triglycerides (VLDL-TG) secretion, hepatic FFA utilization, and lactate production differ among obese subjects with and without MAFLD. Methods: Nine obese subjects with MAFLD and 8 matched subjects without MAFLD (Control) without a history of heart failure and cardiovascular disease were compared before and after 90-min exercise at 50% Peak oxygen consumption. Basal and exercise induced cardiac and hepatic FFA oxidation, uptake and re-esterification and VLDL-TG secretion were measured using [11C]palmitate positron-emission tomography and [1–14C]VLDL-TG. Results: In the heart, increased MOFFA was observed after exercise in MAFLD, whereas MOFFA decreased in Control (basal vs exercise, MAFLD: 4.1 (0.8) vs 4.8 (0.8) μmol·100 ml−1 min−1; Control: 4.9 (1.8) vs 4.0 (1.1); μmol·100 ml−1 min−1, mean (SD), p < 0.048). Hepatic FFA fluxes were significantly lower in MAFLD than Control and increased ≈ two-fold in both groups. VLDL-TG secretion was 50% greater in MAFLD at rest and similarly suppressed during exercise. Plasma lactate increased significantly less in MAFLD than Control during exercise. Conclusions: Using robust tracer-techniques we found that obese subjects with MAFLD do not downregulate MOFFA during exercise compared to Control, possibly due to diminished lactate supply. Hepatic FFA fluxes are significantly lower in MAFLD than Control, but increase similarly with exercise. VLDL-TG export remains greater in MAFLD compared to Control. Basal and post-exercise myocardial and hepatic FFA, VLDL-TG and lactate metabolism is abnormal in subjects with MAFLD compared to Control.

Sider (fra-til)10-18
StatusUdgivet - maj 2023

Bibliografisk note

Funding Information:
This study was supported by The Novo Nordic Foundation (grant numbers NNF18OC0031804 , NNF16OC0021406 ), The Independent Research Fund Denmark (grant number 8020-00420B ), Aarhus University and Steno Diabetes Centre Aarhus, Denmark. Funding sources had no involvement in any part of this study. All authors have read and approved the final manuscript.


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