Exercise increases myocardial free fatty acid oxidation in subjects with metabolic dysfunction-associated fatty liver disease. (May 2023)

• Record Type: Journal Article
• Authors: Risikesan, Jeyanthini; Heebøll, Sara; Kumarathas, Indumathi; Funck, Kristian L.; Søndergaard, Esben; Johansen, Rakel F.; Ringgaard, Steffen; Tolbod, Lars P.; Johannsen, Mogens; Kanstrup, Helle L.; Grønbæk, Henning; Frystyk, Jan; Gormsen, Lars C.; Nielsen, Søren
• Is Part Of: Atherosclerosis. Volume 372(2023)
• Page Start: 10
• Page End: 18
• Publication Date: 2023-05
• Subjects: Fatty liver disease -- MAFLD -- Lipoprotein metabolism -- Free fatty acids -- FFA -- VLDL-Triglycerides -- PET scanning -- Exercise -- PET palmitate Tracer -- VLDL-TG tracer; Arteriosclerosis -- Periodicals; Electronic journals; 616.136
• DOI: 10.1016/j.atherosclerosis.2023.03.015
• Languages: English
• ISSNs: 0021-9150

Abstract

Abstract: 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 [ 11 C]palmitate positron-emission tomography and [1– 14 C]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. Graphical abstract: Image 1 Highlights: Exercise has opposite effects on heart FFA use in subjects with and without MAFLD. Hepatic FFA utilization increases similarly after exercise. VLDL-TG secretion and oxidation rates are greater in subjects with MAFLD. Lactate increase during exercise is significantly impaired in MAFLD.