Journal Articles
Permanent URI for this collectionhttps://mro.massey.ac.nz/handle/10179/7915
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Item Comparative transcriptomes reveal geographic differences in the ability of the liver of plateau zokors (Eospalax baileyi) to respond and adapt to toxic plants(BioMed Central Ltd, 2023-12) Tan Y; Wang Y; Liu Q; Wang Z; Shi S; Su JBACKGROUND: Environmental changes are expected to intensify in the future. The invasion of toxic plants under environmental changes may change herbivore feeding environments. Herbivores living long-term in toxic plant-feeding environments will inevitably ingest plant secondary metabolites (PSMs), and under different feeding environments are likely to have unique protection mechanisms that support improved adaptation to PSMs in their habitat. We aimed to compare different subterranean herbivore population responses and adaptations to toxic plants to unveil their feeding challenges. RESULTS: Here, we investigated the adaptive capacity of the liver in two geographically separated populations of plateau zokors (Eospalax baileyi) before and after exposure to the toxic plant Stellera chamaejasme (SC), at the organ, biochemical, and transcriptomic levels. The results showed no significant liver granules or inflammatory reactions in the Tianzhu (TZ) population after the SC treatment. The transaminase level in the TZ population was significantly lower than that in the Luqu population. Transcriptome analysis revealed that the TZ population exhibited interactions with other detoxification metabolic pathways by oxytocin pathway-associated genes, including diacylglycerol lipase alpha (Dagla), calcium/calmodulin dependent protein kinase II Alpha (Camk2a), and CD38 molecule (Cd38). The phase II process of liver drug metabolism increased to promote the rate of metabolism. We found that alternative splicing (AS) and the expression of the cyclin D (Ccnd1) gene interact-a TZ population hallmark-reduced liver inflammatory responses. CONCLUSION: Our study supports the detoxification limitation hypothesis that differences in liver detoxification metabolism gene expression and AS are potential factors in herbivore adaptation to PSMs and may be a strategy of different herbivore populations to improve toxic plant adaptability.Item Assessment of accuracy of liver fluke diagnostic tests using the gold standard of total worm counts.(Elsevier B.V., 2024-08-24) Dowling A; Lawrence KE; Howe L; Scott I; Pomroy WEIn many regions of New Zealand liver fluke is endemic, infecting most grazing ruminants, including cattle, sheep, and deer. Restricting the economic losses and welfare costs associated with liver fluke relies on accurately identifying those animals with a production limiting infection. This has proven a difficult goal and although several antemortem quantitative tests are available, including faecal egg counts (FEC), serum ELISA and copro-antigen ELISA, none can be considered a gold standard test of liver fluke infection. The accepted gold standard test for fascioliasis is the total fluke count, which is both laborious and can only be completed at post-mortem. This study aimed to compare the performance of four liver fluke diagnostic tests, against the results of a gold standard total fluke count test. Two groups of cattle were selected, 29 culled mixed age beef cows (MAC) and ten 30-month-old steers. The cattle were blood sampled and faecal sampled prior to slaughter and their whole livers recovered post slaughter at the abattoir. Liveweight was also recorded at slaughter. After collection, each liver was weighed, scored for gross pathology, then serum, faeces and livers were frozen at -20 °C for later analysis. Faecal egg counts and F. hepatica copro-antigen ELISA tests were completed on the faecal samples and total fluke counts were completed on the livers. Fasciola hepatica antibody concentration in serum samples were quantified using a commercial ELISA test. Poisson regression models were built to model the association between each diagnostic test and the total fluke count, and a linear regression model was built to examine the relationship between each diagnostic test and live weight at slaughter. The median fluke count was significantly higher in MAC than steers (p = 0.01), and F. hepatica eggs were present in 100% steers and 66% MAC. There was a significant effect of copro-antigen ELISA value on total fluke count (p < 0.0001), with a coproantigen ELISA value = 20.1 predicting 10 flukes and a value = 44.8 predicting 30 flukes. There was also a significant effect of FEC on total fluke count (p = 0.002) but the R-squared value for this model was lower. There was no association between liver fibrosis score or antibody ELISA test and total fluke count (p = 0.95, p = 0.73, respectively). There was a significant effect of total fluke count (p = 0.03) on liveweight at slaughter, with liveweight falling 20.4 kg for each unit increase in loge (total fluke count). There was no effect of FEC (p = 0.11), antibody ELISA (p = 0.55) or copro-antigen ELISA value (p = 0.16) on liveweight at slaughter. Taken together, these results show that the coproantigen ELISA test is the better test for estimating the true liver fluke burden and that the number of flukes in the liver has a negative effect on cattle live weights at slaughter.Item The effect of liver enzymes on adiposity: a Mendelian randomization study.(Springer Nature Limited, 2019-11-14) Liu J; Au Yeung SL; Kwok MK; Leung JYY; Lin SL; Hui LL; Leung GM; Schooling CMPoorer liver function is positively associated with diabetes in Mendelian randomization (MR) studies. Observationally, adiposity is associated with poorer liver function. To clarify the etiology, we assessed the association of liver enzymes with adiposity observationally and using two-sample MR for validation. In the "Children of 1997" birth cohort, we used multivariable linear regression to assess the associations of alanine transaminase (ALT) and alkaline phosphatase (ALP) at ~17.5 years with body mass index (BMI) (n = 3,458). Using MR, genetic predictors of ALT, ALP and gamma glutamyltransferase (GGT), were applied to genome-wide association studies of BMI (n = 681,275), waist circumference (WC) (n = 224,459) and waist-hip ratio (WHR) (n = 224,459) to obtain unconfounded estimates. Observationally, ALT was positively associated with BMI (0.10 kg/m2 per IU/L, 95% confidence interval (CI) 0.09 to 0.11). ALP was inversely associated with BMI (-0.018 kg/m2 per IU/L, 95% CI -0.024 to -0.012). Using MR, ALT was inversely associated with BMI (-0.14 standard deviation per 100% change in concentration, 95% CI -0.20 to -0.07), but not WC or WHR. ALP and GGT were unrelated to adiposity. Poorer liver function might not cause adiposity; instead higher ALT might reduce BMI, raising the question as to the role of ALT in body composition.Item The effect of liver enzymes on body composition: A Mendelian randomization study.(PLOS, 2020-02-11) Liu J; Au Yeung SL; Kwok MK; Leung JYY; Hui LL; Leung GM; Schooling CM; Meyre DBackground Higher alanine transaminase (ALT), indicating poor liver function, is positively associated with diabetes but inversely associated with body mass index (BMI) in Mendelian randomization (MR) studies, suggesting liver function affects muscle mass. To clarify, we assessed the associations of liver enzymes with muscle and fat mass observationally with two-sample MR as a validation. Methods In the population-representative “Children of 1997” birth cohort (n = 3,455), we used multivariable linear regression to assess the adjusted associations of ALT and alkaline phosphatase (ALP) at ~17.5 years with muscle mass and body fat percentage observationally. Genetic variants predicting ALT, ALP and gamma glutamyltransferase (GGT) were applied to fat-free and fat mass in the UK Biobank (n = ~331,000) to obtain unconfounded MR estimates. Results Observationally, ALT was positively associated with muscle mass (0.11 kg per IU/L, 95% confidence interval (CI) 0.10 to 0.12) and fat percentage (0.15% per IU/L, 95% CI 0.13 to 0.17). ALP was inversely associated with muscle mass (-0.03 kg per IU/L, 95% CI -0.04 to -0.02) and fat percentage (-0.02% per IU/L, 95% CI -0.03 to -0.01). Using MR, ALT was inversely associated with fat-free mass (-0.41 kg per 100% in concentration, 95% CI -0.64 to -0.19) and fat mass (-0.58 kg per 100% in concentration, 95% CI -0.85 to -0.30). ALP and GGT were unclearly associated with fat-free mass or fat mass. Conclusion ALT reducing fat-free mass provides a possible pathway for the positive association of ALT with diabetes and suggests a potential target of intervention.ovides a possible pathway for the positive association of ALT with diabetes and suggests a potential target of intervention.Item Impact of Gut Recolonization on Liver Regeneration: Hepatic Matrisome Gene Expression after Partial Hepatectomy in Mice.(MDPI (Basel, Switzerland), 2023-06-28) Amin AR; Hairulhisyam NM; Aqilah RNF; Nur Fariha MM; Mallard BL; Shanahan F; Wheatley AM; Marlini M; Neuman M; Malnick SThe hepatic matrisome is involved in the remodeling phase of liver regeneration. As the gut microbiota has been implicated in liver regeneration, we investigated its role in liver regeneration focusing on gene expression of the hepatic matrisome after partial hepatectomy (PHx) in germ-free (GF) mice, and in GF mice reconstituted with normal gut microbiota (XGF). Liver mass restoration, hepatocyte proliferation, and immune response were assessed following 70% PHx. Hepatic matrisome and collagen gene expression were also analyzed. Reduced liver weight/body weight ratio, mitotic count, and hepatocyte proliferative index at 72 h post PHx in GF mice were preceded by reduced expression of cytokine receptor genes Tnfrsf1a and Il6ra, and Hgf gene at 3 h post PHx. In XGF mice, these indices were significantly higher than in GF mice, and similar to that of control mice, indicating normal liver regeneration. Differentially expressed genes (DEGs) of the matrisome were lower in GF compared to XGF mice at both 3 h and 72 h post PHx. GF mice also demonstrated lower collagen expression, with significantly lower expression of Col1a1, Col1a2, Col5a1, and Col6a2 compared to WT mice at 72 h post PHx. In conclusion, enhanced liver regeneration and matrisome expression in XGF mice suggests that interaction of the gut microbiota and matrisome may play a significant role in the regulation of hepatic remodeling during the regenerative process.Item Dissecting the relationship between plasma and tissue metabolome in a cohort of women with obesity: Analysis of subcutaneous and visceral adipose, muscle, and liver(Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology, 2022-07) Wu ZE; Kruger MC; Cooper GJS; Sequeira IR; McGill A-T; Poppitt SD; Fraser KUntargeted metabolomics of blood samples has become widely applied to study metabolic alterations underpinning disease and to identify biomarkers. However, understanding the relevance of a blood metabolite marker can be challenging if it is unknown whether it reflects the concentration in relevant tissues. To explore this field, metabolomic and lipidomic profiles of plasma, four sites of adipose tissues (ATs) from peripheral or central depot, two sites of muscle tissue, and liver tissue from a group of nondiabetic women with obesity who were scheduled to undergo bariatric surgery (n = 21) or other upper GI surgery (n = 5), were measured by liquid chromatography coupled with mass spectrometry. Relationships between plasma and tissue profiles were examined using Pearson correlation analysis subject to Benjamini-Hochberg correction. Plasma metabolites and lipids showed the highest number of significantly positive correlations with their corresponding concentrations in liver tissue, including lipid species of ceramide, mono- and di-hexosylceramide, sphingomyelin, phosphatidylcholine (PC), phosphatidylethanolamine (PE), lysophosphatidylethanolamine, dimethyl phosphatidylethanolamine, ether-linked PC, ether-linked PE, free fatty acid, cholesteryl ester, diacylglycerol and triacylglycerol, and polar metabolites linked to several metabolic functions and gut microbial metabolism. Plasma also showed significantly positive correlations with muscle for several phospholipid species and polar metabolites linked to metabolic functions and gut microbial metabolism, and with AT for several triacylglycerol species. In conclusion, plasma metabolomic and lipidomic profiles were reflective more of the liver profile than any of the muscle or AT sites examined in the present study. Our findings highlighted the importance of taking into consideration the metabolomic relationship of various tissues with plasma when postulating plasma metabolites marker to underlying mechanisms occurring in a specific tissue.Item Untargeted metabolomics reveals plasma metabolites predictive of ectopic fat in pancreas and liver as assessed by magnetic resonance imaging: the TOFI_Asia study(Springer Nature Limited, 2021-08) Wu ZE; Fraser K; Kruger MC; Sequeira IR; Yip W; Lu LW; Plank LD; Murphy R; Cooper GJS; Martin J-C; Hollingsworth KG; Poppitt SDBACKGROUND: Excess visceral obesity and ectopic organ fat is associated with increased risk of cardiometabolic disease. However, circulating markers for early detection of ectopic fat, particularly pancreas and liver, are lacking. METHODS: Lipid storage in pancreas, liver, abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) from 68 healthy or pre-diabetic Caucasian and Chinese women enroled in the TOFI_Asia study was assessed by magnetic resonance imaging/spectroscopy (MRI/S). Plasma metabolites were measured with untargeted liquid chromatography-mass spectroscopy (LC-MS). Multivariate partial least squares (PLS) regression identified metabolites predictive of VAT/SAT and ectopic fat; univariate linear regression adjusting for potential covariates identified individual metabolites associated with VAT/SAT and ectopic fat; linear regression adjusted for ethnicity identified clinical and anthropometric correlates for each fat depot. RESULTS: PLS identified 56, 64 and 31 metabolites which jointly predicted pancreatic fat (R2Y = 0.81, Q2 = 0.69), liver fat (RY2 = 0.8, Q2 = 0.66) and VAT/SAT ((R2Y = 0.7, Q2 = 0.62)) respectively. Among the PLS-identified metabolites, none of them remained significantly associated with pancreatic fat after adjusting for all covariates. Dihydrosphingomyelin (dhSM(d36:0)), 3 phosphatidylethanolamines, 5 diacylglycerols (DG) and 40 triacylglycerols (TG) were associated with liver fat independent of covariates. Three DGs and 12 TGs were associated with VAT/SAT independent of covariates. Notably, comparison with clinical correlates showed better predictivity of ectopic fat by these PLS-identified plasma metabolite markers. CONCLUSIONS: Untargeted metabolomics identified candidate markers of visceral and ectopic fat that improved fat level prediction over clinical markers. Several plasma metabolites were associated with level of liver fat and VAT/SAT ratio independent of age, total and visceral adiposity, whereas pancreatic fat deposition was only associated with increased sulfolithocholic acid independent of adiposity-related parameters, but not age.