Journal: Nature Communications

Article Title: Sirt6 deficiency in mast cells promotes adipose fibroinflammation in obesity through galectin-3 signaling

doi: 10.1038/s41467-025-66040-z

Figure Lengend Snippet: a , b mRNA levels (a, n = 6 per group) in EAT tissues and protein levels (b, n = 6 per group) in plasma for galectin-1, galectin-3 and galectin-9 in WT and KO mice. c Heatmap displaying the ligand-receptor signaling network of the galectin pathway between immune cell types from WT and KO mice. Each cell in the heatmap represents the predicted communication probability from a sender to a receiver cell type. The bar plot above the heatmap quantifies the total outgoing signaling strength of each cell type, while the bar plot to the right reflects the total incoming signaling strength. TCP, total communication probability. d Bone marrow-derived mast cells (BMMCs) were transfected with control siRNA (siCtrl) or Sirt6 siRNA (siSirt6). Successful Sirt6 silencing was confirmed by qPCR and western blotting ( n = 6 per group). e – i Lgals3 and Lgals9 mRNA levels (e, n = 6 per group), RELA (p65 subunit of NF-κB) binding to the promoters of Lgals3 and Lgals9 ( f , n = 5 per group), Sirt6 binding to the promoters of Lgals3 and Lgasl9 ( g , n = 5 per group), enrichment of Ac-H3K9 on the Lgals3 and Lgals9 promoters ( h , n = 4 per group), and acetylation of H3K9 ( i , n = 3 per group) were compared between control and Sirt6 silenced BMMCs. j , k . Plasma levels of galectin-3 and galectin-9 in human subjects were measured by ELISA ( n = 24 for lean, n = 14 for overweight, n = 6 for obese). A scatter plot was created to examine the correlation between mast cell Sirt6 protein levels and plasma galectin-3 and galectin-9 levels. Values are presented as mean ± SD. Unpaired two-tailed t test between the two groups ( a , b , d , e , i ), one-way ANOVA followed by Sidak’s multiple comparisons analysis ( j , k ) and two-way ANOVA followed by Bonferroni’s post hoc analysis were conducted for statistical analyses ( f – h ). Pearson correlation coefficients were calculated between continuous variables in two-sided distributions ( j , k). Source data are provided as a Source Data file.

Article Snippet: For macrophage migration, mast cell–conditioned medium (MC-CM), obtained from mast cells primed with adipocyte-conditioned medium (adipocyte CM), was added to the lower chamber with or without the galectin-3 inhibitor GB1211 (#HY-147041, MedChemExpress, Monmouth Junction, NJ, USA).

Techniques: Clinical Proteomics, Derivative Assay, Transfection, Control, Western Blot, Binding Assay, Enzyme-linked Immunosorbent Assay, Two Tailed Test

Journal: Nature Communications

Article Title: Sirt6 deficiency in mast cells promotes adipose fibroinflammation in obesity through galectin-3 signaling

doi: 10.1038/s41467-025-66040-z

Figure Lengend Snippet: a Schematic illustration of the adoptive transfer of WT or Sirt6-deficient adipose-derived mast cells (ADMCs), infected with lentivirus carrying shRNA targeting either control shRNA (Lv-eGFP-shCtrl, shCtrl) or galectin-3 (Lv-eGFP-shLgals3, shLgals3), into Kit W-sh/W-sh mice. b – d Body weights during 16 weeks of HFD ( b , n = 6 per group), glucose concentrations during an intraperitoneal glucose tolerance ( c , n = 6 per group) and an insulin tolerance test ( d , n = 6 per group). Areas under the curve during glucose and insulin tolerance tests were compared. Red and pink values on the line in panels ( b , c , and d ) indicate statistical comparisons with the Sirt6 fl/fl MC+shCtrl and Sirt6 -/- MC+shCtrl group, respectively. e EAT sections were stained with H&E or Sirius Red, or immunostained with anti-F4/80 antibody. Representative images and quantification results of adipocyte size in H&E-stained sections ( n = 37 per group) and macrophage numbers in F4/80-immunostained sections ( n = 7 per group) are shown. f Hydroxyproline content in EAT of mice as a measure of fibrosis ( f , n = 6 per group). g EAT sections were immunostained for tryptase, and total and degranulated mast cell counts ( n = 4 per group) were determined ( g ). Values are presented as mean ± SD. Two-way ANOVA followed by Bonferroni’s post hoc analysis ( b – d ) and one-way ANOVA followed by Sidak’s multiple comparisons analysis ( e – g ) were conducted for statistical analyses. Source data are provided as a Source Data file. Panel ( a ) was created in BioRender. H, J. (2025) https://BioRender.com/swlgc9x .

Article Snippet: For macrophage migration, mast cell–conditioned medium (MC-CM), obtained from mast cells primed with adipocyte-conditioned medium (adipocyte CM), was added to the lower chamber with or without the galectin-3 inhibitor GB1211 (#HY-147041, MedChemExpress, Monmouth Junction, NJ, USA).

Techniques: Adoptive Transfer Assay, Derivative Assay, Infection, shRNA, Control, Staining