Zbtb7b defines a compensatory mechanism in MASLD-related HCC progression by suppressing H19-mediated hepatic lipid deposition.

Hepatocellular carcinoma (HCC) is a widely prevalent type of primary liver cancer. However, strategies for pretumor intervention are still limited. In this study, a liver-specific Zbtb7b knockout mouse model was used to evaluate the role of Zbtb7b in metabolic dysfunction-associated steatotic liver disease (MASLD)-related HCC development.

Annonaceous acetogenins mimic AA005 targets mitochondrial trifunctional enzyme alpha subunit to treat obesity in male mice.

Obesity and related diseases pose a major health risk, yet current anti-obesity drugs inadequately addressing clinical needs. Here we show AA005, an annonaceous acetogenin mimic, resists obesity induced by high-fat diets and leptin mutations at non-toxic doses, with the alpha subunit of the mitochondrial trifunctional protein (HADHA) as a target identified through proteomics and in vitro validation. Pharmacokinetic analysis shows AA005 enriches in adipose tissue, prompting the creation of adipose-specific Hadha-deficient mice.

Dietary fructose-mediated adipocyte metabolism drives antitumor CD8 T cell responses.

Fructose consumption is associated with tumor growth and metastasis in mice, yet its impact on antitumor immune responses remains unclear. Here, we show that dietary fructose modulates adipocyte metabolism to enhance antitumor CD8 T cell immune responses and control tumor growth. Transcriptional profiling of tumor-infiltrating CD8 T cells reveals that dietary fructose mediates attenuated transition of CD8 T cells to terminal exhaustion, leading to a superior antitumor efficacy.

Slc7a11 stimulates glutathione synthesis to preserve fatty acid metabolism in primary hepatocytes.

Primary hepatocytes are widely used as a tool for studying metabolic function and regulation in the liver. However, the metabolic properties of primary hepatocytes are gradually lost after isolation. Here, we illustrated that fatty acid metabolism is the major compromised metabolic process in isolated primary hepatocytes, along with drastically decreased GSH and ROS content, while lipid peroxidation is increased.

Yin Yang 1-Induced Long Noncoding RNA DUXAP9 Drives the Progression of Oral Squamous Cell Carcinoma by Blocking CDK1-Mediated EZH2 Degradation.

LncRNAs play a critical role in oral squamous cell carcinoma (OSCC) progression. However, the function and detailed molecular mechanism of most lncRNAs in OSCC are not fully understood. Here, a novel nuclear-localized lncRNA, DUXAP9 (DUXAP9), that is highly expressed in OSCC is identified.

The obesity-induced adipokine sST2 exacerbates adipose T and ILC2 depletion and promotes insulin resistance.

Depletion of fat-resident regulatory T cells (T) and group 2 innate lymphoid cells (ILC2s) has been causally linked to obesity-associated insulin resistance. However, the molecular nature of the pathogenic signals suppress adipose T and ILC2s in obesity remains unknown. Here, we identified the soluble isoform of interleukin (IL)-33 receptor ST2 (sST2) as an obesity-induced adipokine that attenuates IL-33 signaling and disrupts T/ILC2 homeostasis in adipose tissue, thereby exacerbates obesity-associated insulin resistance in mice.

BAF60a deficiency uncouples chromatin accessibility and cold sensitivity from white fat browning.

Brown and beige fat share a remarkably similar transcriptional program that supports fuel oxidation and thermogenesis. The chromatin-remodeling machinery that governs genome accessibility and renders adipocytes poised for thermogenic activation remains elusive. Here we show that BAF60a, a subunit of the SWI/SNF chromatin-remodeling complexes, serves an indispensable role in cold-induced thermogenesis in brown fat.

Landscape of Intercellular Crosstalk in Healthy and NASH Liver Revealed by Single-Cell Secretome Gene Analysis.

Cell-cell communication via ligand-receptor signaling is a fundamental feature of complex organs. Despite this, the global landscape of intercellular signaling in mammalian liver has not been elucidated. Here we perform single-cell RNA sequencing on non-parenchymal cells isolated from healthy and NASH mouse livers.

Long non-coding RNA CCRR controls cardiac conduction via regulating intercellular coupling.

Long non-coding RNAs (lncRNAs) have emerged as a new class of gene expression regulators playing key roles in many biological and pathophysiological processes. Here, we identify cardiac conduction regulatory RNA (CCRR) as an antiarrhythmic lncRNA. CCRR is downregulated in a mouse model of heart failure (HF) and in patients with HF, and this downregulation slows cardiac conduction and enhances arrhythmogenicity.

Long noncoding RNA licensing of obesity-linked hepatic lipogenesis and NAFLD pathogenesis.

Hepatic lipogenesis is aberrantly induced in nonalcoholic fatty liver disease (NAFLD) via activation of the LXR-SREBP1c pathway. To date, a number of protein factors impinging on the transcriptional activity of LXR and SREBP1c have been elucidated. However, whether this regulatory axis interfaces with long noncoding RNAs (lncRNAs) remains largely unexplored.

The long noncoding RNA Blnc1 orchestrates homeostatic adipose tissue remodeling to preserve metabolic health.

Objective: Long noncoding RNAs (lncRNAs) are emerging as powerful regulators of adipocyte differentiation and gene expression. However, their significance in adipose tissue metabolism and physiology has not been demonstrated in vivo. We previously identified Blnc1 as a conserved lncRNA regulator of brown and beige adipocyte differentiation.

Zbtb7b engages the long noncoding RNA Blnc1 to drive brown and beige fat development and thermogenesis.

Brown and beige adipocytes convert chemical energy into heat through uncoupled respiration to defend against cold stress. Beyond thermogenesis, brown and beige fats engage other metabolic tissues via secreted factors to influence systemic energy metabolism. How the protein and long noncoding RNA (lncRNA) regulatory networks act in concert to regulate key aspects of thermogenic adipocyte biology remains largely unknown.

Nrg4 promotes fuel oxidation and a healthy adipokine profile to ameliorate diet-induced metabolic disorders.

Objective: Brown and white adipose tissue exerts pleiotropic effects on systemic energy metabolism in part by releasing endocrine factors. Neuregulin 4 (Nrg4) was recently identified as a brown fat-enriched secreted factor that ameliorates diet-induced metabolic disorders, including insulin resistance and hepatic steatosis. However, the physiological mechanisms through which Nrg4 regulates energy balance and glucose and lipid metabolism remain incompletely understood.

Adsorption of sodium dodecyl sulfate onto precipitate in treatment of vat dark blue BO by dissolved air flotation.

Vat dark blue BO-simulated wastewater was treated by dissolved air flotation (DAF). In this process, the interactions of sodium dodecyl sulfate (SDS) and resulting DAF process precipitates were investigated by infrared spectroscopy and kinetic methods. Fourier transform infrared analysis revealed that γ values (cm) for asymmetric and symmetric stretching vibrations of CH groups for SDS-treated precipitation shifted toward higher in comparison to pure SDS, showing strong SDS and precipitate interactions.

Conserved function of the long noncoding RNA Blnc1 in brown adipocyte differentiation.

Objective: Long noncoding RNAs (lncRNAs) are emerging as important regulators of diverse biological processes. Recent work has demonstrated that the inducible lncRNA Blnc1 stimulates thermogenic gene expression during brown and beige adipocyte differentiation. However, whether Blnc1 is functionally conserved in humans has not been explored.

Expression signature of lncRNAs and their potential roles in cardiac fibrosis of post-infarct mice.

The present study aimed to investigate whether long non-coding RNAs (lncRNAs) are involved in cardiac fibrogenesis induced by myocardial infarction (MI). The differentially expressed lncRNAs and mRNAs in peri-infarct region of mice 4 weeks after MI were selected for bioinformatic analysis including gene ontology (GO) enrichment, pathway and network analysis. Left ventricular tissue levels of lncRNAs and mRNAs were compared between MI and sham control mice, using a false discovery rate (FDR) of <5%.

Reciprocal Changes of Circulating Long Non-Coding RNAs ZFAS1 and CDR1AS Predict Acute Myocardial Infarction.

This study sought to evaluate the potential of circulating long non-coding RNAs (lncRNAs) as biomarkers for acute myocardial infarction (AMI). We measured the circulating levels of 15 individual lncRNAs, known to be relevant to cardiovascular disease, using the whole blood samples collected from 103 AMI patients, 149 non-AMI subjects, and 95 healthy volunteers. We found that only two of them, Zinc finger antisense 1 (ZFAS1) and Cdr1 antisense (CDR1AS), showed significant differential expression between AMI patients and control subjects.

AIF inhibits tumor metastasis by protecting PTEN from oxidation.

Apoptosis-inducing factor (AIF) exerts dual roles on cell death and survival, but its substrates as a putative oxidoreductase and roles in tumorigenesis remain elusive. Here, we report that AIF physically interacts with and inhibits the oxidation of phosphatase and tensin homolog on chromosome ten (PTEN), a tumor suppressor susceptible for oxidation-mediated inactivation. More intriguingly, we also identify PTEN as a mitochondrial protein and the ectopic expression of mitochondrial targeting sequence-carrying PTEN almost completely inhibits Akt phosphorylation in PTEN-deficient cells.

Long Noncoding RNAs: A New Regulatory Code in Metabolic Control.

Long noncoding RNAs (lncRNAs) are emerging as an integral part of the regulatory information encoded in the genome. lncRNAs possess the unique capability to interact with nucleic acids and proteins, and exert discrete effects on numerous biological processes. Recent studies have delineated multiple lncRNA pathways that control metabolic tissue development and function.

The brown fat secretome: metabolic functions beyond thermogenesis.

Brown fat is highly active in fuel oxidation and dissipates chemical energy through uncoupling protein (UCP)1-mediated heat production. Activation of brown fat leads to increased energy expenditure, reduced adiposity, and lower plasma glucose and lipid levels, thus contributing to better homeostasis. Uncoupled respiration and thermogenesis have been considered to be responsible for the metabolic benefits of brown adipose tissue.

The brown fat-enriched secreted factor Nrg4 preserves metabolic homeostasis through attenuation of hepatic lipogenesis.

Brown fat activates uncoupled respiration in response to cold temperature and contributes to systemic metabolic homeostasis. To date, the metabolic action of brown fat has been primarily attributed to its role in fuel oxidation and uncoupling protein 1 (UCP1)-mediated thermogenesis. Whether brown fat engages other tissues through secreted factors remains largely unexplored.

A long noncoding RNA transcriptional regulatory circuit drives thermogenic adipocyte differentiation.

Brown and beige/brite fats generate heat via uncoupled respiration to defend against cold. The total mass and activity of thermogenic adipose tissues are also tightly linked to systemic energy and nutrient homeostasis. Despite originating from distinct progenitors, brown and beige adipocytes acquire remarkably similar molecular and metabolic characteristics during differentiation through the action of a network of transcription factors and cofactors.