Impaired liver regeneration of steatotic rats after portal vein ligation: A particular emphasis on 99mTc-DISIDA scintigraphy and adiponectin signaling

Hsiao, Ing-Tsung; Lin, Kun-Ju; Chang, Shi-Ing; Yen, Tzu-Chen; Chen, Tse-Ching; Yeh, Ta-Sen

doi:10.1016/j.jhep.2010.01.005

« Previous Next »Journal of Hepatology
Volume 52, Issue 4 , Pages 540-549, April 2010

Impaired liver regeneration of steatotic rats after portal vein ligation: A particular emphasis on ^99mTc-DISIDA scintigraphy and adiponectin signaling

Ing-Tsung Hsiao
- Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan, Taiwan
- Both contributed equally.
Kun-Ju Lin
- Departments of Nuclear Medicine and Molecular Imaging Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan
- Both contributed equally.
Shi-Ing Chang
- Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan, Taiwan
Tzu-Chen Yen
- Departments of Nuclear Medicine and Molecular Imaging Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan
Tse-Ching Chen
- Department of Pathology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
Ta-Sen Yeh
- Department of Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan
- Corresponding author. Address: Department of Surgery, Chang Gung Memorial Hospital, 5 Fu-Hsing Street, Kwei-Shan Shiang, Taoyuan 886-3, Taiwan. Tel.: +886 3281200x3219; fax: +886 3 3285818.

Received 22 April 2009; received in revised form 2 September 2009; accepted 3 September 2009. published online 19 February 2010.

Background & Aims

Portal vein ligation (PVL) is increasingly employed prior to major hepatectomy in order to enhance the volume of the future liver remnant (FLR) and to avoid post-hepatectomy liver failure. The efficacy of PVL on subjects with non-alcohol fatty liver disease (NAFLD) is largely unknown.

Methods

Sprague–Dawley rats fed with normal diet (control) and methionine-choline deficient diet (MCD) were used. The animals underwent PVL and were sacrificed at indicated time points.

Results

Livers from MCD rats exhibited a decreased BrdU and Ki-67 labelling index, and an increased apoptotic index after PVL compared to normal rats; as a net effect, MCD rats exhibited a decrease in their restituted liver mass and redistributed volume ratio, compared to normal rats. Normal rats displayed similar serum levels of ICG15-R before and after PVL; whereas MCD rats displayed reduced ICG15-R after PVL. Using ^99mTc-DISIDA scintigraphy examination, livers from MCD rats exhibited decreased HEF and prolonged TE_1/2 of FLR after PVL, indicating deteriorating hepatocyte function despite the shift in volume. The basal level of plasma TNFα, IL-1α, IL-1β, and IL-10 of MCD rats was significantly increased before PVL compared to normal rats; however their plasma level did not increase in response to PVL as in normal rats. Hepatic adiponectin mRNA surged in MCD rats after PVL, whereas its receptors, AdipoR1 and AdipoR2, were paradoxically down-regulated. PPARα, a down-stream molecule of AdipoR2 axis, was also decreased in MCD rats.

Conclusions

Reduced regenerated liver mass and deteriorated hepatocyte function of the FLR from steatotic rats after PVL may be associated with deranged Kupffer cell-mediated cytokine expression and disrupted adiponectin signalling.

Abbreviations: PVL, portal vein ligation, FLR, future liver remnant, NAFLD, non-alcohol fatty liver disease, BrdU, bromodeoxyuridine, MPO, myeloperoxidase, ALT, alanine aminotransferase, MCD, methionine-choline deficiency diet, ICG-R15, indocyanine green 15′ retention test, DISIDA, diisopropyl iminodiacetic acid, ROI, region of interest, HEF, hepatic extraction fraction, AdipoR1, adiponectin receptor type 1, AdipoR2, adiponectin receptor type 2, TE_1/2, excretion half time