Prof. Zsolt Radak Profile

Prof. Zsolt Radak

at Hungarian Univ. of Sports Science

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Proceedings Article | 12 March 2024 Poster + Paper

Combined NAD(P)H and lipofuscin FLIM revealed the development of metabolic syndrome in the liver of epigenetically altered rats

A. Kolonics, T. Kawamura, R. Szipőcs, Z. Radak

Proceedings Volume 12849, 1284909 (2024) https://doi.org/10.1117/12.3005632

KEYWORDS: Liver, Mitochondria, Fluorescence lifetime imaging, Animals, Statistical analysis, Muscles, Tissues, Metabolism

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Low physical performance is closely associated with skeletal muscle dysfunction and metabolic disorders such as obesity, diabetes and cardiovascular disease. The aim of the present study was to characterize the differences in liver mitochondrial function in an aged rat model with congenital low and high running capacity (LCR/HCR) of generation 44. In addition to monitoring basal and succinate-mediated H₂O₂-induced fluorescence, NAD(P)H and lipofuscin fluorescence lifetime imaging (FLIM) was applied in frozen rat liver tissue. Reduced VO₂max, increased muscle wasting and increased body mass were observed in LCR compared to HCR rats. Succinate load suggested a deterioration of intact liver mitochondria in LCR rats: ROS production was greater, accompanied by a limited NADH increase at the same mitochondrial membrane potential (ΔΨ_m). Complex I- and Complex II-driven ADP-coupled ATP production was the same. The NAD(P)H lifetime of cytosol at LCR rats significantly shifted toward free NAD(P)H lifetime values (G_max= 0,60 ± 0,03) compared to normal young rats (G_max= 0,54 ± 0,04) indicating a sensitive transition from oxidative phosphorylation to glycolysis. Interestingly, the shift was more pronounced in case of HCR rats (G_max= 0,69 ± 0,03). In conclusion, age shifts metabolism from oxidative phosphorylation to glycolysis in liver. The beneficial epigenetic difference coupled to high running capacity helps to slow the deterioration of physical and mitochondrial fitness, as reflected in the irreversible accumulation of the oxidative stress marker lipofuscin. Accordingly, NAD(P)H and lipofuscin FLIM imaging may provide a sensitive, predictive approach to study early effects of metabolic syndrome and ageing.

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