Impaired BCAA catabolism in adipose tissues promotes age-associated metabolic derangement.

Adipose tissues are central in controlling metabolic homeostasis and failure in their preservation is associated with age-related metabolic disorders. The exact role of mature adipocytes in this phenomenon remains elusive. Here we describe the role of adipose branched-chain amino acid (BCAA) catabolism in this process.

Longitudinal study investigating serum metabolites and their association with type 2 diabetes risk in a Korean population.

Aim: The lack of longitudinal metabolomics data and the statistical techniques to analyse them has limited the understanding of the metabolite levels related to type 2 diabetes (T2D) onset. Thus, we carried out logistic regression analysis and simultaneously proposed new approaches based on residuals of multiple logistic regression and geometric angle-based clustering for the analysis in T2D onset-specific metabolic changes.

Materials And Methods: We used the sixth, seventh and eighth follow-up data from 2013, 2015 and 2017 among the Korea Association REsource (KARE) cohort data.

Enhanced Glutaminolysis Drives Hypoxia-Induced Chemoresistance in Pancreatic Cancer.

Unlabelled: Pancreatic ductal adenocarcinoma (PDAC) exhibits severe hypoxia, which is associated with chemoresistance and worse patient outcome. It has been reported that hypoxia induces metabolic reprogramming in cancer cells. However, it is not well known whether metabolic reprogramming contributes to hypoxia.

Associations between local acidosis induced by renal LDHA and renal fibrosis and mitochondrial abnormalities in patients with diabetic kidney disease.

During the progression of diabetic kidney disease (DKD), renal lactate metabolism is rewired. The relationship between alterations in renal lactate metabolism and renal fibrosis in patients with diabetes has only been partially established due to a lack of biopsy tissues from patients with DKD and the intricate mechanism of lactate homeostasis. The role of lactate dehydrogenase A (LDHA)-mediated lactate generation in renal fibrosis and dysfunction in human and animal models of DKD was explored in this study.

Integrated metagenomics and metabolomics analysis illustrates the systemic impact of the gut microbiota on host metabolism after bariatric surgery.

Aim: To explore how bariatric surgery (BS) modified the obesity-associated gut microbiome, the host metabolome, and their interactions in obese Korean patients.

Materials And Methods: Stool and fasting blood samples were obtained before and 1, 3, 6, and 12 months after BS from 52 patients enrolled in the Korean Obesity Surgical Treatment Study. We analysed the gut microbiome by 16S rRNA gene sequencing and the serum metabolome, including bile acids, by nuclear magnetic resonance spectroscopy and ultrahigh-performance liquid chromatography/triple quadrupole mass spectrometry.

A novel role of CRTC2 in promoting nonalcoholic fatty liver disease.

Objective: Diet-induced obesity is often associated with nonalcoholic fatty liver disease (NAFLD), which instigates severe metabolic disorders, including cirrhosis, hepatocellular carcinoma, and type 2 diabetes. We have shown that hepatic depletion of CREB regulated transcription co-activator (CRTC) 2 protects mice from the progression of diet-induced fatty liver phenotype, although the exact mechanism by which CRTC2 modulates this process is elusive to date. Here, we investigated the role of hepatic CRTC2 in the instigation of NAFLD in mammals.

Glutathione is an aging-related metabolic signature in the mouse kidney.

The ability to maintain systemic metabolic homeostasis through various mechanisms represents a crucial strength of kidneys in the study of metabolic syndrome or aging. Moreover, age-associated kidney failure has been widely accepted. However, efforts to demonstrate aging-dependent renal metabolic rewiring have been limited.

Purine metabolite-based machine learning models for risk prediction, prognosis, and diagnosis of coronary artery disease.

Alterations in xanthine oxidase activity are known to be pathologically influential on coronary artery disease (CAD), but the association between purine-related blood metabolites and CAD has only been partially elucidated. We performed global metabolomics profiling and network analysis on blood samples from the Wonju and Pyeongchang (WP) cohort study (n = 2055) to elucidate the importance of purine related metabolites associated with potential CAD risk. Then, 5 selected serum metabolites were quantified from the WP cohort, Shinchon cohort (n = 259), and Shinchon case control (n = 424) groups to develop machine learning models for 10-year risk prediction, relapse within 10 years and diagnosis of the disease via 100 repeated 5-fold cross-validations of logistic models.

Temporal fluxomics reveals oscillations in TCA cycle flux throughout the mammalian cell cycle.

Cellular metabolic demands change throughout the cell cycle. Nevertheless, a characterization of how metabolic fluxes adapt to the changing demands throughout the cell cycle is lacking. Here, we developed a temporal-fluxomics approach to derive a comprehensive and quantitative view of alterations in metabolic fluxes throughout the mammalian cell cycle.

Analysis of population-specific pharmacogenomic variants using next-generation sequencing data.

Functional rare variants in drug-related genes are believed to be highly differentiated between ethnic- or racial populations. However, knowledge of population differentiation (PD) of rare single-nucleotide variants (SNVs), remains widely lacking, with the highest fixation indices, (F values), from both rare and common variants annotated to specific genes, having only been marginally used to understand PD at the gene level. In this study, we suggest a new, gene-based PD method, PD of Rare and Common variants (PDRC), for analyzing rare variants, as inspired by Generalized Cochran-Mantel-Haenszel (GCMH) statistics, to identify highly population-differentiated drug response-related genes ("pharmacogenes").

Correlation estimation with singly truncated bivariate data.

Correlation coefficient estimates are often attenuated for truncated samples in the sense that the estimates are biased towards zero. Motivated by real data collected in South Sudan, we consider correlation coefficient estimation with singly truncated bivariate data. By considering a linear regression model in which a truncated variable is used as an explanatory variable, a consistent estimator for the regression slope can be obtained from the ordinary least squares method.

Analysis of pharmacogenomic variants associated with population differentiation.

In the present study, we systematically investigated population differentiation of drug-related (DR) genes in order to identify common genetic features underlying population-specific responses to drugs. To do so, we used the International HapMap project release 27 Data and Pharmacogenomics Knowledge Base (PharmGKB) database. First, we compared four measures for assessing population differentiation: the chi-square test, the analysis of variance (ANOVA) F-test, Fst, and Nearest Shrunken Centroid Method (NSCM).