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Resting and Exercise Energy Metabolism After Liver Transplantation for Nonalcoholic Steatohepatitis.

ABSTRACT: Nonalcoholic steatohepatitis (NASH) is a leading indication for liver transplantation (LT). We hypothesized that weight gain after LT may be exacerbated by reduced metabolic rates due to the LT procedure, particularly during exercise. We aimed to compare resting and exercise energy expenditure between patients transplanted for NASH and nontransplant nonalcoholic fatty liver disease (NAFLD) subjects.NASH LT recipients (>1-year post, n = 14) and NAFLD controls (n = 13) underwent analysis of body composition, resting energy expenditure (REE), and exercise energy expenditure (VO2max), the latter using a ramped-Bruce protocol assessed by expired gas analysis and peak heart rate.Participants were mean 61.5 ± 7.9 years, 48.1% men, and 66.7% white. Baseline comorbidities were similar between groups. Among men, mean REE adjusted for total (17.7 vs 18.8, P = 0.87) and lean body mass (23.5 vs 26.9, P = 0.26), as well as VO2 (20.1 vs 23.9, P = 0.29), was lower in NASH LT recipients compared with NAFLD controls, respectively, although not statistically significant. However, female NASH LT recipients had significantly lower mean REE than NAFLD controls when adjusted for total (14.2 vs 18.9, P = 0.01) and lean body mass (19.3 vs 26.5, P = 0.002), as well as significantly lower VO2max (14.4 vs 20.6, P = 0.017).NASH LT recipients, particularly women, have lower REE and exercise energy expenditure compared with nontransplant NAFLD patients. More aggressive diet and exercise programs for post-LT NASH recipients to account for reduced resting and exercise metabolic rates may attenuate weight gain in this vulnerable population.

SUBMITTER: Levitsky J

PROVIDER: S-EPMC5540626 | biostudies-other | 2017 Aug

REPOSITORIES: biostudies-other

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Project description:Objective: Changes in bile acids (BAs) are increasingly recognized as potential targets for non-alcoholic steatohepatitis (NASH). Kaempferol has been proved to be anti-inflammatory and reduce the disorder of lipid metabolism. In order to analyze the BA profile in NASH mice and determine the predictive biomarkers of kaempferol treatment, serum-targeted metabolomics and liver tissue RNA sequencing (RNA-seq) were carried out. Design: Six normal control mice (NC group), eight HFD-fed mice (HFD group), and eight kaempferol-treated HFD-fed mice (HFD + KP group) were included in the present study. Ultra-performance liquid chromatography coupled to a tandem mass spectrometry system (UPLC-MS/MS) was used to quantify serum and liver BAs, and RNA-seq was used to quantify liver differentially expressed genes related to BA metabolism. Results: The serum levels of CA, βMCA, UDCA, and 12-DHCA, as well as ωMCA in both the serum and liver, were significantly decreased in the HFD group compared with those in the NC group, and kaempferol can increase the serum levels of βMCA, UDCA, and ωMCA and the liver level of 12-DHCA. The serum levels of TDCA, THDCA, TUDCA, TDCA/CA, and TDCA/DCA were significantly increased in the HFD group compared with those of the NC group, and kaempferol can decrease them. Furthermore, NASH mice had a higher liver level of total CA%, total CDCA%, primary BAs/secondary BAs, 12α-OH BAs/non-12α-OH Bas, and conjugated BAs/unconjugated BAs, and all decreased after kaempferol treatment. According to the RNA-seq results, we found that compared with the NC group, the mRNA expression of cholesterol-7α-hydroxylase (CYP7A1) in the HFD group was significantly increased, and the mRNA expression of sterol 12α-hydroxylase (CYP8B1) and multidrug resistance-related protein 3 (MRP3) was significantly decreased, while kaempferol significantly promoted the mRNA expression of mitochondrial sterol 27-hydroxylase (CYP27A1) and Na+ -taurocholate cotransporting polypeptide (NTCP). Conclusion: βMCA, CA, UDCA, 12-DHCA, ωMCA, CDCA, TωMCA, TDCA, THDCA, TCDCA, and TUDCA in the serum, as well as 6,7-diketoLCA, 12-DHCA, and ωMCA in the liver, may be potential biomarkers for kaempferol to improve NASH. HFD-induced NASH may be associated with the increase of CYP7A1 and the decrease of CYP8B1, leading to increased BA synthesis, and the decrease of MRP3 leading to decreased BA synthesis, and kaempferol may alleviate NASH by increasing CYP27A1 and NTCP to enhance BA transport.

Project description:Nonalcoholic steatohepatitis (NASH) is one of the top 3 indications for liver transplantation (LT) in Western countries. It is unknown whether renal dysfunction at the time of LT has any effect on post-LT outcomes in recipients with NASH. From the United Network for Organ Sharing-Standard Transplant Analysis and Research data set, we identified 4088 NASH recipients who received deceased donor LT. We divided our recipients a priori into 3 categories: group 1 with estimated glomerular filtration rate (eGFR) <30 mL/minute/1.73 m2 at the time of LT and/or received dialysis within 2 weeks preceding LT (n = 937); group 2 with recipients who had eGFR ≥30 mL/minute/1.73 m2 and who did not receive renal replacement therapy prior to LT (n = 2812); and group 3 with recipients who underwent simultaneous liver-kidney transplantation (n = 339). We examined the association of pretransplant renal dysfunction with death with a functioning graft, all-cause mortality, and graft loss using competing risk regression and Cox proportional hazards models. The mean ± standard deviation age of the cohort at baseline was 58 ± 8 years, 55% were male, 80% were Caucasian, and average exception Model for End-Stage Liver Disease score was 24 ± 9. The median follow-up period was 5 years (median, 1816 days; interquartile range, 1090-2723 days). Compared with group 1 recipients, group 2 recipients had 19% reduced trend for risk for death with a functioning graft (subhazard ratio [SHR], 0.81; 95% confidence interval [CI], 0.64-1.02) and similar risk for graft loss (SHR, 1.25; 95% CI, 0.59-2.62), whereas group 3 recipients had similar risk for death with a functioning graft (SHR, 1.23; 95% CI, 0.96-1.57) and graft loss (SHR, 0.18; 95% CI, 0.02-1.37) using an adjusted competing risk regression model. In conclusion, recipients with preserved renal function before LT showed a trend toward lower risk of death with a functioning graft compared with SLKT recipients and those with pretransplant severe renal dysfunction in patients with NASH.

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Resting and Exercise Energy Metabolism After Liver Transplantation for Nonalcoholic Steatohepatitis.

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