Given the increasing prevalence of obesity, the white-to-beige adipocyte conversion has attracted interest as a target for obesity treatment. Gamma-aminobutyric acid (GABA) treatment can reduce obesity, but the underlying mechanism remains unclear. Here, we aimed to investigate the mechanism by which GABA triggers weight loss by improving the beiging of inguinal white adipose tissue (iWAT) and the role of gut microbiota in this process. The results showed that GABA reduced body weight and adipose inflammation and promoted the expression of thermogenic genes in the iWAT. The 16S rRNA sequence analysis of gut microbiota showed that GABA treatment increased the relative abundance of Bacteroidetes, Akkermansia, and Romboutsia and reduced that of Firmicutes and Erysipelatoclostridium in obese mice. Additionally, serum metabolomic analysis revealed that GABA treatment increased 3-hydroxybutyrate and reduced oxidized lipid levels in obese mice. Spearman’s correlation analysis showed that Akkermansia and Romboutsia were negatively associated with the levels of oxidized lipids. Fecal microbiota transplantation analysis confirmed that the gut microbiota was involved in the white-to-beige adipocyte reconstruction by GABA. Overall, our findings suggest that GABA treatment may promote iWAT beiging through the gut microbiota in obese mice. GABA may be utilized to protect obese people against metabolic abnormalities brought on by obesity and gut dysbiosis.

Tissue spatial interaction in the liver, including the interplay among immune cells, blood vessels, sinusoidal endothelial cells, bile ducts, stellate cells, hepatic progenitor cells, and hepatocytes, is crucial not only for normal organogenesis but also for disease development. Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the most prevalent liver disease, with heterogeneous mechanisms involving cross-talk between hepatocytes and stromal cells under metabolic stress, inflammation, and fibrosis. Developing 3D coculture liver organoid platforms provides novel insights into the complex links of cell communication during disease progression. Thus, we recapitulate liver organoids as models for indicating reconstructed inter-tissue interactions of MASLD, highlighting the potential of transplanting liver organoids as a therapeutic application.

Introduction: Ischemic stroke, a prevalent cerebrovascular disorder characterized by reduced cerebral blood flow, and systemic lupus erythematosus (SLE), an autoimmune disease affecting various organs, are suspected to share overlapping etiological mechanisms and genetic predispositions. This study aimed to identify shared diagnostic biomarkers and molecular mechanisms by analyzing datasets from the GEO database.Methods: We pinpointed differentially expressed genes using the limma package and identified co-expression modules associated with both conditions using Weighted Gene Coexpression Network Analysis. Pathway enrichment analysis was conducted using GO and KEGG to identify co-driver genes. LASSO regression was applied to evaluate potential diagnostic markers, and immune cell infiltration was quantified using the CIBERSORT computational method. A middle cerebral artery occlusion (MCAO) mouse model was developed to assess core gene expression in vivo.Results: We identified 69 shared driver genes linked to stroke and SLE, which were narrowed down to the top 10 genes through a Protein-Protein Interaction network analysis with Cytoscape. LASSO regression selected EIF2AK2, PARP9, and IFI27 as diagnostic biomarkers, supported by ROC curve analysis. Immune cell infiltration profiles were nearly identical between ischemic stroke and SLE. 9.4T MR imaging, H&E and Nissl staining confirmed ischemic stroke in the MCAO model, and qPCR analysis confirmed elevated expression of the three hub genes.Discussion: Our findings provide evidence for common diagnostic indicators and disease mechanisms in ischemic stroke and SLE, offering novel insights for potential therapeutic strategies targeting their shared immune cell infiltration microenvironments.