Preoperative Beta-Hydroxy-Beta-Methyl-Butyrate Supplementation Reduces Mitochondrial Dynamics Proteins and Preserves Hepatic Mitochondrial Function After Partial Hepatectomy in Mice.

AIM: The liver exhibits a remarkable regenerative capacity, enabling this organ to maintain homeostasis even after significant injury. However, hepatic regeneration requires sufficient energy to sustain cellular hypertrophy and proliferation, thus ensuring efficient tissue repair. Therefore, dietary modulation of pathways regulating mitochondrial quality may enhance liver regeneration. This study aimed to investigate the effects of preoperative beta-hydroxy-beta-methylbutyrate (HMB) supplementation on mitochondrial quality control pathways and its impact on the liver regeneration process in mice undergoing partial hepatectomy (PHx).

METHODS

Male C57BL/6J mice were supplemented with 600 mg/kg HMB via gavage for 10 days. On the 10th day, supplementation was discontinued, and the mice underwent a ⅔ liver resection. The subsequent 7 days have constituted the liver regeneration period. For a second injury induction, at the end of the 7th day of regeneration, acetaminophen (APAP) overdose was administered via gavage. We then analyzed several markers of mitochondrial quality and liver function.

RESULTS

Our results indicate that preoperative HMB supplementation modulates cell cycle progression, preventing excessive hepatic mass accumulation. Additionally, HMB regulates mitochondrial dynamics by decreasing Parkin, Mfn2, and DRP1 protein levels while increasing the mitochondrial markers VDAC2 and Tom20. Following a second injury from an APAP overdose, the HMB-supplemented group demonstrated increased mtDNA content and enhanced mitochondrial capacity, both critical for effective tissue recovery.

CONCLUSION

Our findings suggest that preoperative HMB supplementation preserves hepatic mitochondrial capacity after PHx.