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Kolonics 2023 MiP2023

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MiPschool 2023

Kolonics 2023 MiP2023

Kolonics Attila
Accelerated epigenetic changes may contribute to the development of metabolic syndrome revealed by NADH FLIM.

Link: MiP2023 Obergurgl AT

Kolonics Attila (2023)

Event: MiP2023 Obergurgl AT

Authors:Kolonics Attila, Kawamura T, Szipoecs R, Radak Z

Aging leads to a loss of muscle mass and a decline in skeletal muscle function (1) leading to imbalance between glucose and lipid metabolism (2). Low exercise capacity is highly correlated with skeletal muscle dysfunction and metabolic disorders (3). Age-associated factors intrinsic to the muscle, including defects in NAD+ synthesis (4), reduced mitochondrial copy number (5), and epigenomic changes affecting the expression of metabolic genes (6) reported. We aimed to characterize mitochondrial fitness of liver in an inborn low- versus high-capacity runners (LCR/HCR) aged female rats to study the spread of metabolic dysfunction.
LCR/HCR rats (44th generation, 24 months old) used were artificially selected from genetically heterogeneous N:NIH stock (7). NAD(P)H lifetime imaging (FLIM) characterized liver metabolism in frozen tissues; basal and succinate induced ROS production was evaluated by Amplex Red in the presence of horseradish peroxidase, ΔΨmt by TMRE in intact liver mitochondria.
HCR group was less vulnerable to metabolic disorder comparing to LCR group proofed by decreased body mass and increased VO2max. It was further supported by mitochondrial analysis of intact liver mitochondria. Basal ROS production showed no difference between LCR and HCR groups although succinate induced ROS production was higher in LCR group at identical ΔΨmt. NAD(P)H FLIM uncovered subtle alterations: LCR groups had significantly less free NADH comparing to HCR groups (Fig.1).
In conclusion, epigenetic changes induced decline of metabolism correlated with deterioration of liver mitochondrial fitness. Succinate induced ROS-production at same membrane potential negatively correlated with free NADH-level.

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Figure 1. Low intrinsic running capacity promotes shifts toward more bound and less free NADH. TFLIM color maps of liver from HCR and LCR illustrate a significant depletion in free NADH level shown as the color shifts from more green (free NADH) to red (bound NADH) of NADH lifetime parallel with lower intensity of total NADH grayscale image (A). Summary of phasor plots from 5 animals from each groups shows the shift in distribution from free to bound NADH in liver cells of LCR comparing to HCR groups. Pure, free NADH with lifetime of 0.4 ns is shown by green circle and bound NADH with lifetime of 3.4 ns with a red circle on the semicircle. (B). Data are mean ± SD and were compared by Student T-test *p < 0.05 (C).


Kolonics Attila1,3, Kawamura T2, Szipöcs R3, Radák Z1
  1. Research Center of Molecular Exercise Science, Univ. of Physical Education, Hungary
  2. Waseda Institute for Sport Science, Waseda University, Japan
  3. Institute for Solid State Physics and Optics of Wigner RCP, Hungary
Corresponding author: [email protected]

Labels: Pathology: Aging;senescence 

Organism: Rat  Tissue;cell: Liver 

Event: E2