Hippo-YAP/TAZ signalling coordinates adipose plasticity and energy balance by uncoupling leptin expression from fat mass.

Adipose tissues serve as an energy reservoir and endocrine organ, yet the mechanisms that coordinate these functions remain elusive. Here, we show that the transcriptional coregulators, YAP and TAZ, uncouple fat mass from leptin levels and regulate adipocyte plasticity to maintain metabolic homeostasis. Activating YAP/TAZ signalling in adipocytes by deletion of the upstream regulators Lats1 and Lats2 results in a profound reduction in fat mass by converting mature adipocytes into delipidated progenitor-like cells, but does not cause lipodystrophy-related metabolic dysfunction, due to a paradoxical increase in circulating leptin levels. Mechanistically, we demonstrate that YAP/TAZ-TEAD signalling upregulates leptin expression by directly binding to an upstream enhancer site of the leptin gene. We further show that YAP/TAZ activity is associated with, and functionally required for, leptin regulation during fasting and refeeding. These results suggest that adipocyte Hippo-YAP/TAZ signalling constitutes a nexus for coordinating adipose tissue lipid storage capacity and systemic energy balance through the regulation of adipocyte plasticity and leptin gene transcription.

Donor body mass index over 30 is no barrier for pure laparoscopic donor right hepatectomy.

Backgrounds/Aims: Challenges arise when translating pure laparoscopic donor right hepatectomy (PLDRH) results from Asian to Western donors, due to differences in body mass index (BMI). This study compares the outcomes of PLDRH and conventional open donor right hepatectomy (CDRH) in donors with BMI over 30. Methods: Medical records of live liver donors (BMI > 30) undergoing right hepatectomy (2010-2021) were compared: 25 PLDRH cases vs. 19 CDRH cases. Donor and recipient demographics, operative details, and outcomes were analyzed. Results: PLDRH and CDRH had similar donor and recipient characteristics. PLDRH had longer liver removal and warm ischemic times, but a shorter post-liver removal duration than CDRH. Donor complication rates were comparable, with the highest complication being grade IIIa in PLDRH, necessitating needle aspiration for biloma on postoperative day 11. Fortunately, this donor fully recovered without additional treatment. No complications exceeding Clavien-Dindo grade IIIa occurred in either group. Recipient outcomes between the groups were similar. Conclusions: This study supports PLDRH as a viable option for donors with BMI over 30, challenging the notion that high BMI should deter considering PLDRH. The findings provide valuable insights into the safety and feasibility of PLDRH, encouraging further exploration of this technique in diverse donor populations.

Impact of typhoons on anthropogenic nitrogen sources in Lake Sihwa, South Korea.

This study investigated the nitrate dual isotopic compositions (δ15NNO3 and δ18ONO3) of water samples to trace nitrate sources in Lake Sihwa, which encompasses various land-use types (e.g., urban, industry, wetland, and agriculture). The biogeochemical interactions of anthropogenic nitrogen sources (e.g., soil, road dust, and septic water) were also evaluated through multiple pathways from terrestrial boundaries to the water column. Based on increased concentrations of dissolved total nitrogen (DTN; 3.1 ± 1.6 mg/L) after typhoon, the variation of element stoichiometry (N:P:Si) in this system shifted to the relatively N-rich conditions (DIN/DIP; 14.1 ± 8.1, DIN/DSi; 1.4 ± 1.8), potentially triggering the occurrence of harmful algal blooms. Furthermore, discriminative isotopic compositions (δ15NNO3; 4.0 ± 2.1 ‰, δ18ONO3; 6.1 ± 4.3 ‰) after the typhoon suggested the increased DTN input of anthropogenic origins within Lake Sihwa would be mainly transported from urban sources (76 ± 9 %). Consequently, the isotopic-based approach may be useful for effective water quality management under increased anthropogenic activities near aquatic systems.

Inhibitory Regulation of FOXO1 in PPARδ Expression Drives Mitochondrial Dysfunction and Insulin Resistance.

Forkhead box O1 (FOXO1) regulates muscle growth, but the metabolic role of FOXO1 in skeletal muscle and its mechanisms remain unclear. To explore the metabolic role of FOXO1 in skeletal muscle, we generated skeletal muscle-specific Foxo1 inducible knockout (mFOXO1 iKO) mice and fed them a high-fat diet to induce obesity. We measured insulin sensitivity, fatty acid oxidation, mitochondrial function, and exercise capacity in obese mFOXO1 iKO mice and assessed the correlation between FOXO1 and mitochondria-related protein in the skeletal muscle of patients with diabetes. Obese mFOXO1 iKO mice exhibited improved mitochondrial respiratory capacity, which was followed by attenuated insulin resistance, enhanced fatty acid oxidation, and improved skeletal muscle exercise capacity. Transcriptional inhibition of FOXO1 in peroxisome proliferator-activated receptor δ (PPARδ) expression was confirmed in skeletal muscle, and deletion of PPARδ abolished the beneficial effects of FOXO1 deficiency. FOXO1 protein levels were higher in the skeletal muscle of patients with diabetes and negatively correlated with PPARδ and electron transport chain protein levels. These findings highlight FOXO1 as a new repressor in PPARδ gene expression in skeletal muscle and suggest that FOXO1 links insulin resistance and mitochondrial dysfunction in skeletal muscle via PPARδ.

Impact of Preformed Donor-specific Antibodies in Comparison to ABO Incompatibility in Living Donor Liver Transplantation: A Propensity Score-Matched Analysis.

BACKGROUND: Immunological factors play a pivotal role in the outcomes of solid organ transplantation. We aimed to elucidate the effects of donor-specific antibodies (DSAs) and ABO compatibility on living donor liver transplantation (LDLT) outcomes. METHODS: A retrospective analysis was conducted on 584 LDLT recipients from 2015 to 2020. The recipients were stratified into 3 groups: ABO-compatible recipients without DSAs (group 1), ABO-compatible recipients with DSAs (group 2), and ABO-incompatible recipients without DSAs (group 3). Propensity score matching was used for balanced comparisons. RESULTS: In the matched comparisons, group 2 exhibited a higher incidence of T cell-mediated rejection compared with group 1 (22.7% versus 4.5%, P  = 0.030). Despite this, the 5-y survival rates were similar between groups 1 and 2 (81.6% versus 95.5%, P  = 0.085). Group 3, in comparison with group 1, showed elevated rates of cytomegalovirus infection (23.2% versus 7.3%, P  = 0.008), T cell-mediated rejection (28.0% versus 7.3%, P  = 0.001), and antibody-mediated rejection (13.4% versus 0%, P  = 0.001). However, the survival rates were comparable between group 3 and group 1 (82.0% versus 86.5%, P  = 0.220, respectively). Comparisons between group 2 and group 3 did not reveal significant differences in postoperative outcomes or survival rates ( P  > 0.05). CONCLUSIONS: DSA positivity and ABO incompatibility contribute to distinct posttransplant complications in LDLT. The integrated consideration of both factors in pretransplant assessment may enhance risk stratification and inform tailored interventions. Further research is required to corroborate these findings and provide mechanistic insights.

Atmospheric mercury uptake and accumulation in forests dependent on climatic factors.

The environmental and climatic factors dictating atmospheric mercury (Hg) uptake by foliage and accumulation within the forest floor are evaluated across six mountain sites, South Korea, using Hg concentration and Hg stable isotope analyses. The isotope ratios of total gaseous Hg (TGM) at six mountains are explained by local anthropogenic Hg emission influence and partly by mountain elevation and wind speed. The extent to which TGM is taken up by foliage is not dependent on the site-specific TGM concentration, but by the local wind speed, which facilitates TGM passage through dense deciduous canopies in the Korean forests. This is depicted by the significant positive relationship between wind speed and foliage Hg concentration (r2 = 0.92, p < 0.05) and the magnitude of δ202Hg shift from TGM to foliage (r2 = 0.37, p > 0.05), associated with TGM uptake and oxidation by foliar tissues. The litter and topsoil Hg concentrations and isotope ratios reveal relationships with a wide range of factors, revealing lower Hg level and greater isotopic fractionation at sites with low elevation, high wind speed, and high mean warmest temperature. We attribute this phenomenon to active TGM re-emission from the forest floor at sites with high wind speed and high temperature, caused by turnover of labile organic matter and decomposition. In contrast to prior studies, we observe no significant effect of precipitation on forest Hg accumulation but precipitation appears to reduce foliage-level Hg uptake by scavenging atmospheric Hg species available for stomata uptake. The results of this study would enable better prediction of future atmospheric and forest Hg influence under climate change.

Identifying the external N and Hg inputs to the estuary ecosystem based on the triple isotopic information (δ15NNO3, Δ17ONO3 and δ18ONO3).

The supply and sources of N and Hg in the Geum estuary of the western coast of Korea were evaluated. Triple isotope proxies (δ15NNO3, Δ17ONO3 and δ18ONO3) of NO3- combined with conservative mixing between river and ocean waters were used to improve isotope finger-printing methods. The N pool in the Geum estuary was primarily influenced by the Yellow Sea water, followed by riverine discharge (821 × 106 mol yr-1) and atmospheric deposition (51 × 106 mol yr-1). The influence of the river was found to be greater for Hg than that of the atmosphere. The triple isotope proxies revealed that the riverine and atmospheric inputs of N have been affected by septic wastes and fossil fuel burning, respectively. From the inner estuary towards offshore region, the influence of the river diminishes, thus increasing the relative impact of the atmosphere. Moreover, the isotope proxies showed a significant influence of N assimilation in February and nitrification in May.

Quantitative source tracking for organic foulants in ultrafiltration membrane using stable isotope probing approach.

Quantitatively identifying the primary sources of organic membrane fouling is essential for the effective implementation of membrane technology and optimal water resource management prior to the treatment. This study leveraged carbon stable isotope tracers to estimate the quantitative contributions of various organic sources to membrane fouling in an ultrafiltration system. Effluent organic matter (EfOM) and aquatic natural organic matter (NOM), two common sources, were combined in five different proportions to evaluate their mixed effects on flux decline and the consequent fouling behaviors. Generally, biopolymer (BP) and low molecular weight neutral (LMWN) size fractions - abundantly present in EfOM - were identified as significant contributors to reversible and irreversible fouling, respectively. Fluorescence spectroscopy disclosed that a protein-like component notably influenced overall membrane fouling, whereas humic-like components were predominantly responsible for irreversible fouling rather than reversible fouling. Fluorescence index (FI) and biological index (BIX), common fluorescence source tracers, showed promise in determining the source contribution for reversible foulants. However, these optical indices were insufficient in accurately determining individual source contributions to irreversible fouling, resulting in inconsistencies with the observed hydraulic analysis. Conversely, applying a carbon stable isotope-based mixing model yielded reasonable estimates for all membrane fouling. The contribution of EfOM surpassed 60 % for reversible fouling and increased with its content in DOM source mixtures. In contrast, aquatic NOM dominated irreversible fouling, contributing over 85 %, regardless of the source mixing ratios. This study emphasizes the potential of stable isotope techniques in accurately estimating the contributions of different organic matter sources to both reversible and irreversible membrane fouling.