Biology subjects

Staels, B.

Publications and source records attributed to Staels, B..

15 recordsLinked to original sources

bioRxiv2026

Rev-erbα inhibits vascular calcification by repressing osteogenic reprogramming in atherosclerosis

Background: Atherosclerotic plaque rupture is the most deleterious atherogenic event, responsible for the majority of fatal acute atherothrombotic and myocardial infarctions. Intimal microcalcification is a major cause of atherosclerotic plaque instability. Yet, a thorough characterization of the mechanisms controlling intimal calcification is needed to develop innovative therapeutic strategies to treat high risk patients. The nuclear receptor Rev-erb regulates lipoprotein metabolism and exerts anti-inflammatory activities. Here, we hypothesized that Rev-erb modulates atherogenesis by regulating arterial calcification processes. Methods: We used a multi-omics approach in the ANGIOSAFE and the ATHEROPORTAL human cohort to identify pathways and factors associated with vascular calcification in diabetic patients. We then compared REV-ERB expression between calcified and non-calcified areas of human endarterectomies using laser capture microdissection assays (n=11-22/group). We assessed the role of Rev-erb on calcium deposition and expression of osteoblast markers in aortic roots of 18-month-old Ldlr-/-Rev-erb-/- and Ldlr-/-Rev-erb+/+ mice (n=10/group). Rev-erb-dependent molecular pathways that drive calcification were identified using gene expression profiling in aortic plaques from Ldlr-/-Rev-erb-/- and Ldlr-/-Rev-erb+/+ mice (n=8-10/group). We then confirmed omics data using primary aortic smooth muscle cells (SMCs) (n=3-6) in vitro assessing inflammation-driven calcification process as well as Rev-erb-dependent transcriptional mechanisms. Results: REV-ERB expression is significantly lower in circulating anti-inflammatory classical CD14+CD16- monocytes from diabetic patients with low coronary artery calcium (CAC) compared to those exhibiting high CAC scores while its expression is lower in highly calcified plaques from patients with diabetes mellitus compared to those with no diabetes or no calcification. Consistently, REV-ERB is markedly downregulated in calcified areas of human endarterectomy samples, while remaining higher in non-calcified regions. Rev-erb deficient Ldlr-/- mice exhibit accelerated atherogenesis and vascular calcification, and aortic smooth muscle cells (SMCs) exhibit a reprogramming toward an osteochondroblastic phenotype. Functional in vitro studies show that Rev-erb maintains SMC identity by preventing their IL-1{beta}-driven transdifferentiation into osteochondroblast-like cells, notably through the repression of key osteogenic regulators. Finally, while hyaluronic acid degradation is known to promote intimal calcification, we demonstrate that Rev-erb represses the hyaluronidase Cemip expression during SMC transdifferentiation. Conclusions: Rev-erb is identified as an important brake on SMC-driven vascular calcification, suppressing both osteogenic reprogramming and matrix-remodeling pathways. Thus, this study opens new avenues for developing novel therapeutic tools targeting Rev-erb to reduce vascular calcification and associated cardiovascular risk in high-risk patients.

pathology↗

bioRxiv2026

The constitutive androstane receptor protects against metabolic dysfunction-associated steatotic liver disease through sex specific interactions with the gut microbiota

Background: The gut-liver axis is involved in Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD), but the host molecular actors involved in such dialogue have not yet been fully characterized. Objective: We investigated the sex-dependent role of the Constitutive Androstane Receptor (CAR) as a hepatic sensor of microbial signals in MASLD pathophysiology. Design: Male and female Car+/+ and Car-/- mice were fed a western diet (WD) for 4, 14 or 35 weeks. We performed plasma biochemistry, liver histology, bile acid and cholesterol quantification, untargeted multi-omics approach combining liver RNA-sequencing and 16S rRNA sequencing, together with co-housing, fecal microbiota transplantation and analysis of publicly available transcriptomics data in human cohorts. Results: Short-term WD revealed CAR-dependent protection against steatosis, together with perturbations in the transcriptional signatures of multiple transcription factors involved in hepatocyte identity in males. After 14 weeks, CAR deletion increased WD-induced liver damage, inflammation and fibrosis, and disrupted bile acid, cholesterol and gut microbiota homeostasis, in males only. Co-housing and fecal microbiota transplantations revealed that a Car+/+ gut microbiota protected against WD-induced liver damage, while a Car-/- microbiota was reshaped by a Car+/+ host. No CAR-dependent phenotype was observed in females. Finally, in human cohorts, hepatic CAR expression decreased in advanced clinical stages of MASLD. Conclusion: CAR is a sex-dependent protective nuclear receptor against MASLD progression, acting both as a transcriptional regulator of hepatocyte identity and as a mediator of the host-microbiota crosstalk.

physiology↗

bioRxiv2026

PPARα-dependent effects in the liver and jejunum of mice in response to pemafibrate

Peroxisome proliferator-activated receptor (PPAR) is a nuclear receptor that plays a central role in metabolic adaptation by regulating gene expression programs involved in lipid utilization and energy homeostasis. Although the hepatic functions of PPAR and its target genes are well characterized, less is known about its transcriptional activity in extrahepatic tissues. Pemafibrate (K-877), a selective PPAR modulator (SPPARM), is a high-affinity PPAR ligand with improved potency and selectivity compared with conventional fibrates. Here, we investigated pemafibrate-induced tissue-specific transcriptional responses comparing wild type and whole-body PPAR-deficient littermate mice. Twelve-week-old male PPAR+/+ and PPAR-/- mice were treated daily with pemafibrate (0.1 mg/kg) or vehicle by oral gavage for 14 days. We performed genome-wide transcriptomic analyses in the liver, jejunum, kidney, soleus muscle, and BAT. Pemafibrate-induced transcriptional changes were entirely dependent on PPAR, as no differentially expressed genes were detected in PPAR-/- mice. The magnitude and nature of the response were tissue-specific, with the strongest transcriptional effects observed in the liver and jejunum, whereas the kidney, soleus muscle, and BAT showed limited responses. In the liver, pemafibrate primarily induced the expression of genes involved in fatty acid metabolism, mitochondrial function, and energy production. In the jejunum, pemafibrate activated lipid metabolic programs together with tissue-specific pathways related to cellular homeostasis. Collectively, our findings show that pemafibrate is a highly selective PPAR activator with a preferential transcriptional activity in the liver and intestine after oral administration. This study provides a resource for defining tissue-specific PPAR-responsive gene networks and expands our understanding of PPAR functions beyond the liver.

pharmacology and toxicology↗

bioRxiv2026

Experimental and mathematical models reveal that AMPK modulates circadian clock gene expression and period through NAD+-dependent regulation of Bmal1

The circadian clock allows living systems to anticipate environmental daily variations by scheduling cellular mechanisms according to the time of the day. The reciprocal interplay between metabolism and circadian clock is essential for energy homeostasis, and the disruption of metabolic clock inputs contributes to dysfunction of clocks in peripheral tissues. However, the molecular mechanisms through which the feeding/fasting cycle entrains peripheral clocks remain incompletely understood. Here, we investigate experimentally and theoretically the role of AMP-dependent kinase (AMPK), a key fasting sensor, in metabolic regulation of the circadian clock. Using a luciferase reporter driven by the Bmal1 promoter to monitor molecular clock activity in human U2OS cells, and thanks to a signal processing method based on the Hilbert transform to retrieve the instantaneous phase and period of circadian signals, we show that pharmacological activation of AMPK by AICAR significantly elevates Bmal1 promoter activity and markedly lengthens the clock period in a dose-dependent manner. Conversely, the clock period is shortened by the pharmacological inhibition by SR18292 of Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1-alpha). Importantly, the action of AICAR is abolished by FK866, a nicotinamide phosphoribosyltransferase (NAMPT) inhibitor, demonstrating that AMPK-dependent modulation of Bmal1 promoter activity requires NAD+ availability. These experimental results are recapitulated by numerical simulations of our previously published mathematical model, where PGC-1-alpha plays a key role in mediating AMPK activity to the clock. Moreover, the comparison of experimentally measured and theoretically predicted phase response curves, following AMPK activation at different circadian phases, provides an additional validation of the model. By integrating biological experiments with mathematical modeling, our results identify a key mechanism through which metabolic factors can entrain and regulate the circadian clock via NAD+-dependent AMPK-mediated regulation of Bmal1 promoter activity.

cell biology↗

bioRxiv2026

Hypothalamic Farnesoid X Receptor deficiency alters energy balance by modulating hepatic glucose production and adipose tissue metabolism through central insulin signaling.

Objectives: The bile acid nuclear receptor Farnesoid X Receptor (FXR, NR1H4) is a major regulator of metabolism and energy homeostasis in peripheral organs. It modulates bile acid, glucose, and lipid metabolism, as well as fat mass and body weight. However, FXR is also expressed in the brain, particularly in the hypothalamus, a key center for the regulation of energy homeostasis. Although one study has demonstrated a role for brain FXR activation in energy balance, its specific hypothalamic role is still unknown. Here, we examined the role of FXR in the mediobasal hypothalamus in the regulation of energy balance. Methods: We used a genetic approach combined with metabolic phenotyping to determine the effect of FXR invalidation in the mediobasal hypothalamus on metabolic parameters involved in the central regulation of energy homeostasis. Results: Our results demonstrate that hypothalamic FXR deficiency induces a positive energy balance, resulting in a reduction in energy expenditure due to alterations in glucose metabolism accompanied by structural changes in white adipose tissues. Conclusion: This study uncovers a previously unrecognized role for hypothalamic FXR in the central homeostatic control of energy balance, providing new insights into its contribution to peripheral glucose metabolism and adipose tissue structural remodeling.

physiology↗

bioRxiv2026

A multimodal framework for immune cell annotation across blood and tissue single-cell data

AbstractAccurate cell annotation remains a central challenge in single-cell analysis, particularly when datasets contain rare populations, transitional states, and tissue-adapted phenotypes. We previously developed scODIN as an expert-guided framework for immune cell annotation in single-cell RNA-sequencing data. Here, we present pyODIN, a major extension of this framework for Python. pyODIN supports multimodal annotation using RNA, antibody-derived tag (ADT), or combined RNA-ADT information. It also substantially expands the annotation database from a CD4 T-cell-centred framework to a broader cell-type reference resource spanning major and minor peripheral blood cell populations as well as tissue-associated subsets. We benchmarked pyODIN against CellTypist, MMoCHi and HiCAT using independently curated immune reference datasets. pyODIN demonstrated the highest overall classification accuracy, and at the top-lineage level, pyODIN reduced cross-lineage errors relative to the benchmark methods. At finer resolution, pyODIN preserved substantially greater CD4 T-cell subtype structure than CellTypist and HiCAT, resolving regulatory, follicular, helper, memory, and cytotoxic states that were collapsed into broader categories by the comparator methods. In a controlled marker-ablation experiment, pyODIN outperformed MMoCHi when key lineage-defining RNA markers were removed from the expression feature set, and the addition of ADT information restored NK and CD8 T-cell annotation, demonstrating the value of multimodal annotation when transcript-level evidence is incomplete. Finally, application to liver fine-needle aspirate data showed that the expanded framework supports annotation beyond PBMC datasets. Together, pyODIN provides an expert-guided, adaptable cell annotation framework for Python, designed for multimodal cell phenotyping across blood and tissue single-cell datasets. pyODIN is freely available at https://github.com/SondergaardLab/pyODIN.

immunology↗

bioRxiv2025

Deep learning models reading clinical data and liver omics strongly distinguish NASH from steatosis and suggest new genes involved in liver disease severity

Background & AimsMetabolic dysfunction-associated steatotic liver disease (MASLD, previously NAFLD) is a frequent co-morbidity of obesity and diabetes, with prevalence increasing worldwide in all age groups and both sexes. Only early stages of the disease are fully reversible. Recognising liver disease stages and elucidating the molecular underpinning of their progression are thus medically important. We developed a deep learning model to recognise simple steatosis from steatohepatitis combining liver transcriptomics, epigenetics, and clinical data. MethodsWe used clinical data, liver gene expression and liver DNA methylation gathered from 300 patients with obesity of the ABOS cohort (80 without NAFLD, 137 with simple steatosis, 83 with steatohepatitis). We selected non-redundant clinical variables, gene expressions and CpGs methylation levels most associated with severity using unsupervised approaches. We designed a multi-module, multi-layer perceptron to predict patients liver status. We trained five model instances on independent training/test sets and combined the predictions. ResultsWe used a score based on gene expression/DNA methylation and relevant principal component analysis (PCA) loadings to select 200 genes and 260 CpG methylations. Models trained on the three modalities reached an AUC of 0.945 overall on a validation set with accuracies above 81% for simple steatosis and 88% for NASH, outperforming any other machine learning model so far. We retrieved patient clusters previously found using clinical variables in the latent space of our clinical data module, but not in the gene expression and DNA methylation modules. While all three modules are needed to reach the best prediction accuracy in all classes, the gene expression module had the most impact on the decision. Independent models weighted gene expression inputs similarly, shining light on their importance. The most impactful genes were linked to immune responses and extracellular matrix. However, many of those genes were previously unassociated with steatotic liver disease onset or progression. ConclusionsA multi-omics deep-learning model can recognise steatohepatitis from simple liver steatosis with an AUC of 0.945 and identify new genes potentially involved in NAFLD progression. Gene expressions profiles predicting disease severity are largely different from those specific of clinical variable clusters. Impact and implicationsThis study suggests that clinical variables are not sufficient to recognise the severity of steatotic liver disease with high accuracy, but model efficiency increases when used together with liver epigenetics and transcriptomics.

molecular biology↗

bioRxiv2025

The Circadian Clock Controls Hepatic Stellate Cell Activation in Liver Fibrosis via a BMAL1/CK1ϵ/REV-ERBα/Transgelin Signaling Pathway.

Liver fibrosis is a progressive and life-threatening condition with no effective targeted treatments. Growing evidence indicates a two-way relationship between circadian rhythm and fibrogenesis, although the specific molecular signaling pathways involved are still not well understood. The molecular clock, which governs circadian rhythms, regulates metabolic and cellular functions, and its pharmacological manipulation has shown potential as a therapy for organ fibrosis. Although the livers molecular clock appeared resilient to the progression of chronic liver disease in humans from steatosis to fibrosis, detectable changes in the daily amplitude of clock genes were observed in a cohort of people living with obesity. We discovered a clock-controlled signaling pathway that drives hepatic stellate cell (HSC) activation, a key event in fibrosis progression. Interfering with this pathway, either by disrupting the core regulator CLOCK:BMAL1 or activating the nuclear receptors REV-ERBs, significantly reduced HSC activation. We also identified transgelin as the downstream effector of clock-regulated HSC contractility, a characteristic of HSC activation. Transgelin is regulated indirectly by a BMAL1-CK1{varepsilon} signaling pathway and directly by REV-ERB. Our findings identify a previously unknown circadian-controlled mechanism that links the molecular clock to HSC activation and cell contractile function, which is relevant to human diseases. This pathway provides several entry points for drugs to target and disrupt fibrogenic signaling. By connecting clock biology to the cellular processes that cause fibrosis, our work also offers a mechanistic basis for chronotherapeutic strategies against chronic liver disease.

molecular biology↗

bioRxiv2024

CytoBatchNorm: an R package with graphical interface for batch effects correction of cytometry data

Innovation in cytometry propelled it to an almost "omic" dimension technique during the last decade. The application fields concomitantly enlarged, resulting in generation of high-dimensional high-content data sets which have to be adequately designed, handled and analyzed. Experimental solutions and detailed data processing pipelines were developed to reduce both the staining conditions variability between samples and the number of tubes to handle. However, an unavoidable variability appears between samples, barcodes, series and instruments (in multicenter studies) contributing to "batch effects" that must be properly controlled. Computer aid to this aim is necessary, and several methods have been published so far, but configuring and carrying out batch normalization remains unintuitive for scientists with "pure" academic backgrounds in biology. To address this challenge, we developed an R package called CytoBatchNorm that offers an intuitive and user-friendly graphical interface. Although the processing is based on the script by Schuyler et al., the graphical interface revolutionizes its use. CytoBatchNorm enables users to define a specific correction for each marker in a single run. It provides a graph that guides you through quickly setting the correction for each marker. It allows corrections to be previewed and inter-marker effects to be checked as the settings are made. CytoBatchNorm will help the cytometry community to adequately scale data between batches, reliably reducing batch effects and improving subsequent dimension reduction and clustering. VISUAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=129 SRC="FIGDIR/small/596492v1_ufig1.gif" ALT="Figure 1"> View larger version (46K): org.highwire.dtl.DTLVardef@600a1eorg.highwire.dtl.DTLVardef@13860cborg.highwire.dtl.DTLVardef@5ad915org.highwire.dtl.DTLVardef@6218dc_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

bioRxiv2024

Crosstalk interactions between transcription factors ERRalpha and PPARalpha assist PPARalpha-mediated gene expression

The peroxisome proliferator-activated receptor (PPAR) is a crucial transcription factor governing genes associated with fatty acid {beta}-oxidation. How various interacting proteins modulate PPARs transcriptional function remains incompletely understood. Employing an unbiased mammalian protein-protein interaction trap with liganded PPAR as bait, we identified an interaction with the orphan nuclear receptor estrogen-related receptor (ERR). Random mutagenesis scanning of PPARs ligand-binding domain and coregulator profiling experiments implicated bridging coregulators, while in vitro studies suggested a trimeric interaction involving RXR. The PPAR{middle dot}ERR interaction, dependent on three C-terminal residues within ERRs helix 12, was reinforced by PGC1 and serum deprivation. Pharmacological inhibition of ERR reduced its interaction with ligand-activated PPAR, revealing a transcriptome indicative of ERR functioning as a transcriptional repressor on prototypical PPAR target genes. Intriguingly, ERR exhibited opposite behavior on other PPAR targets, including the isolated PDK4 enhancer. Chromatin immunoprecipitation analyses demonstrated PPAR ligand-dependent recruitment of ERR onto specific chromatin regions where PPAR binds in mouse livers. These findings highlight intricate transcriptional crosstalk mechanisms between PPAR and ERR, suggesting a multi-layered regulatory network fine-tuning PPARs activity as a nutrient-sensing transcription factor.

molecular biology↗

bioRxiv2023

Time-of-day-dependent variation of the hepatic transcriptome and metabolome is disrupted in non-alcoholic fatty liver disease patients

Liver homeostasis is ensured in part by time-of-day-dependent processes, many of them being paced by the molecular circadian clock. Liver functions are compromised in non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH), and clock disruption increases susceptibility to non-alcoholic fatty liver disease (NAFLD) progression in rodent models. We therefore investigated whether time-of-day-dependent transcriptome and metabolome are significantly altered in human NAFL and NASH livers. Liver biopsies, collected within an 8 hour- window from a carefully phenotyped cohort of 290 patients and histologically diagnosed to be either normal, NAFL or NASH hepatic tissues, were analyzed by RNA sequencing and unbiased metabolomic approaches. Time-of-day-dependent gene expression patterns and metabolomes were identified and compared between histologically normal, NAFL and NASH livers. We provide here a first-of-its-kind report of a daytime-resolved human liver transcriptome-metabolome and associated alterations in NAFLD. Transcriptomic analysis showed a robustness of core molecular clock components in NAFL and NASH livers. It also revealed stage-specific, time-of-day- dependent alterations of hundreds of transcripts involved in cell-to-cell communication, intra- cellular signaling and metabolism. Similarly, rhythmic amino acid and lipid metabolomes were affected in pathological livers. Both TNFa and PPAR{gamma} signaling are predicted as important contributors to altered rhythmicity. NAFLD progression to NASH perturbs time-of-day-dependent processes in human livers, while core molecular clock component differential expression is maintained.

genomics↗

bioRxiv2023

A time- and space-resolved nuclear receptor atlas in mouse liver

The unique functional versatility of the liver is paramount for organismal homeostasis. Both liver development and adult functions are controlled by tightly regulated transcription factor networks, within which nuclear receptors regulate essential functions of parenchymal and non-parenchymal cells. Acting as transcription factors sensitive to extracellular cues such as steroidal hormones, lipid metabolites, xenobiotics... and modulated by intracellular signaling pathways, nuclear receptors orchestrate many aspects of hepatic physiology. While liver functional zonation and adaptability to fluctuating conditions are known to rely on a sophisticated cellular architecture, a comprehensive knowledge of nuclear receptor functions in the different liver cell types is still lacking. As a first step toward the accurate mapping of nuclear receptor functions in mouse liver, we characterized their levels of expression in whole liver as a function of time and diet, and explored nuclear receptor isoform expression in hepatocytes, cholangiocytes, Kupffer cells, hepatic stellate cells and liver sinusoidal cells. In addition, we leveraged liver single cell RNAseq studies to provide here an up-to-date compendium of nuclear receptor expression in mouse liver in space and time.

molecular biology↗

bioRxiv2022

The HDAC inhibitor trichostatin A impairs pancreatic β-cell function through an epigenome-wide reprogramming

ObjectiveThe pancreatic islets of Langerhans contain distinct cell subtypes including insulin-producing {beta} cells. Although their cell-specific gene expression pattern defines their identity, the underlying molecular network driving this transcriptional specificity is not fully understood. Among the numerous transcriptional regulators, histone deacetylases (HDAC) enzymes are potent chromatin modifiers which directly regulate gene expression through deacetylation of lysine residues within specific histone proteins. The precise molecular mechanisms underlying HDAC effects on cellular plasticity and {beta}-cell identity are currently unknown. MethodsThe pharmacological inhibition of HDAC activity by trichostatin A (TSA) was studied in the mouse Min6 and human EndocBH1 cell lines, as well as primary mouse sorted {beta} cells and human pancreatic islets. The molecular and functional effects of treating these complementary {beta}-cell models with TSA was explored at the epigenomic and transcriptomic level through next-generation sequencing of chromatin immunoprecipitation (ChIP) assays (ChIP-seq) and RNA sequencing (RNA-seq) experiments, respectively. ResultsWe showed that TSA alters insulin secretion associated with {beta}-cell specific transcriptome programming in both mouse and human {beta}-cell lines, as well as on human pancreatic islets. We also demonstrated that this alternative {beta}-cell transcriptional program in response to HDAC inhibition is related to an epigenome-wide remodeling at both promoters and enhancers. ConclusionsTaken together, our data indicate that full HDAC activity is required to safeguard the epigenome, to protect against loss of {beta}-cell identity with unsuitable expression of genes associated with alternative cell fates.

genomics↗

bioRxiv2021

Rev-erb-α controls skeletal muscle calcium homeostasis through myoregulin repression: implications in Duchenne Muscular Dystrophy

The sarcoplasmic reticulum (SR) plays an important role in calcium homeostasis. SR calcium mishandling is described in pathological conditions such as myopathies. Here, we investigated whether the nuclear receptor Rev-erb- regulates skeletal muscle SR calcium homeostasis. Our data demonstrate that Rev-erb invalidation in mice impairs SERCA-dependent SR calcium uptake. Rev-erb- acts on calcium homeostasis by repressing the SERCA inhibitor Myoregulin, through direct binding to its promoter. Restoration of Myoregulin counteracts the effects of REV-ERB- overexpression on SR calcium content. Interestingly, myoblasts from Duchenne myopathy patients display downregulated REV-ERB expression, whereas pharmacological Rev-erb activation ameliorates SR calcium homeostasis, and improves muscle structure and function in dystrophic mdx/Utr+/- mice. Our findings demonstrate that Rev-erb- regulates muscle SR calcium homeostasis, pointing to its therapeutic interest for mitigating myopathy.

cell biology↗

bioRxiv2020

The hepatic compensatory response to elevated systemic sulfide impairs medium chain fat oxidation and promotes diabetes

Impaired hepatic glucose and lipid metabolism are hallmarks of type-2 diabetes. Increased sulfide production from cysteine, or sulfide-donor compounds, may beneficially regulate hepatic metabolism. Disposal of sulfide through the sulfide oxidation pathway (SOP) is critical for maintaining sulfide within a safe physiological range. We show that mice lacking the liver-enriched mitochondrial SOP enzyme thiosulfate sulfur-transferase (Tst-/- mice) exhibit high circulating sulfide, increased gluconeogenesis, hypertriglyceridemia and fatty liver, despite whole-body insulin-sensitisation. Unexpectedly, hepatic sulfide levels were normal in Tst-/- mice, a result of homeostatic induction of mitochondrial sulfide disposal and glutathione excretion associated with net suppression of protein persulfidation and nuclear respiratory factor-2 target proteins. Proteomic and persulfidomic profiling converged on gluconeogenesis and hepatic lipid metabolism and revealed a selective deficit in medium-chain fatty acid oxidation in Tst-/- mice. We reveal a critical role for TST in hepatic metabolism that raises implications for sulfide-donor strategies in the context of liver function and metabolic disease.

physiology↗