PhD Scientific Days 2024

Poster Session O - Surgical Medicine

Exercise promotes functional liver regeneration through the AMPK pathway following partial hepatectomy in rats

Text of the abstract

Introduction: The only curative treatment for locally extensive liver tumors is surgical resection. Insufficient future liver remnant after major hepatectomy, however, deteriorates the surgical outcome due to post-hepatectomy liver failure. Therefore, by enhancing the regenerative capacity of the liver physical prehabilitation can improve the postoperative outcome after hepatectomy. Yet, the molecular mechanisms are not fully understood. The adenosine monophosphate-activated protein kinase (AMPK) is a key molecule in liver regeneration that improves the course of liver diseases.
Aims: We aimed to investigate the role of exercise-induced AMPK in liver regeneration after partial hepatectomy.
Method: Male Wistar rats divided into sedentary (S), physical prehabilitation (P) and physical prehabilitation followed by AMPK inhibition (PI) groups underwent partial hepatectomy. Morphological regeneration was assessed by liver weight, Ki67 index and MR volumetry. Functional regeneration was evaluated by standard laboratory parameters, indocyanin green secretion and 99mTc-mebrofenin hepatobiliary scintigraphy. To investigate the postoperative outcome endotoxemia model was established.
Results: Hepatocyte proliferation (p < 0.01) and liver function (p < 0.001) improved, while mortality (p < 0.001) reduced in the P group compared to the S group. AMPK inhibition abolished the beneficial effect of physical prehabilitation on liver function (p < 0.001) and postoperative outcome (p < 0.001). However, morphological regeneration (p < 0.05) was more pronounced in the PI group compared to the P group.
Conclusion: Exercise-induced AMPK activation has a central role in functional liver regeneration. Further investigation is needed to develop exercise mimetics for vulnerable patients who can not participate in physical prehabilitation programs.
Funding: Semmelweis University 250+ PhD Excellence Grant (38973/DIDIT/2024); New National Excellence Program of the Ministry for Culture and Innovation from the source of the National Research, Development and Innovation Fund (ÚNKP-22-3-I-SE-2)