Journal: Metabolism: clinical and experimental

Article Title: Serum Response Factor (SRF) promotes actin cytoskeletal organization in adipocytes to support adaptive hypertrophic expansion and tissue remodeling during obesity in mice

doi: 10.1016/j.metabol.2026.156548

Figure Lengend Snippet: Critical role of SRF in regulating actin cytoskeletal gene expression in adipocytes in vitro . (A) Motif identified by MEME that is enriched in H3K27ac peaks within the HFD-associated super-enhancer regions. (B) Alignment of the SRF binding motif identified de novo from SRF ChIP-Seq in TGFβ1-treated 3T3L1 adipocytes, compared to the canonical SRF motif from the HOMER database. (C) Pathway analysis of genes associated with SRF ChIP-seq peaks. (D) Genomic tracks showing SRF and H3K27ac ChIP-seq signals at the Acta2 locus, highlighting SRF binding induced by TGFβ1 treatment (indicated by a black arrow) within an adipocyte super-enhancer region. (E–G) In vitro loss- and gain-of function experiments in 3T3-L1 adipocytes. Gene expression analysis of cytoskeletal genes following (E) Srf knockdown ( shSrf , n = 3 per condition, total N = 6) and (F) overexpression ( Srf OE, n = 3 per condition, total N = 6). (G) Western blot analysis of SRF and ACTA2 protein levels upon Srf overexpression ( Srf OE, n = 2 per condition, total N = 4). A two-tailed Student’s t -test was used for statistical analysis. * P < 0.05, ** P < 0.01, *** P < 0.001.

Article Snippet: For generation of SRF knockout mice specific to beige and brown adipocytes (SRF-BKO), Srf -flox mice were crossed with Ucp1 -Cre mice (Jackson Laboratory, 024670).

Techniques: Gene Expression, In Vitro, Binding Assay, ChIP-sequencing, Knockdown, Over Expression, Western Blot, Two Tailed Test

Journal: Metabolism: clinical and experimental

Article Title: Serum Response Factor (SRF) promotes actin cytoskeletal organization in adipocytes to support adaptive hypertrophic expansion and tissue remodeling during obesity in mice

doi: 10.1016/j.metabol.2026.156548

Figure Lengend Snippet: Role of SRF in actin filament structure and cellular expansion in adipocytes in vivo during obesity. (A) Body weight trajectories of wild-type (WT, n = 11) and tamoxifen-inducible, adipocyte-specific Srf KO (SRF-AKO, n = 9) male mice during HFD feeding. Total N = 20. (B) Heatmap showing the relative expression of cytoskeletal and collagen genes in eWAT from WT ( n = 6) and SRF-AKO male mice ( n = 5). Total N = 11. (C) Phalloidin staining of actin filaments in isolated adipocytes from WT and SRF-AKO male mice (scale bar: 20 μm). (D–E) Co-staining of isolated adipocytes with phalloidin (red) and PLIN1 (green) from both eWAT and iWAT of female mice. Scale bar: 100 μm, with quantification of phalloidin signal intensity. (F–G) Representative H&E-stained adipose tissue sections from (F) eWAT and (G) iWAT of WT and SRF-AKO male mice, with quantification of average adipocyte size. Scale bar: 100 μm. A two-tailed Student’s t -test was used for statistical analysis. ** P < 0.01, *** P < 0.001, **** P < 0.0001.

Article Snippet: For generation of SRF knockout mice specific to beige and brown adipocytes (SRF-BKO), Srf -flox mice were crossed with Ucp1 -Cre mice (Jackson Laboratory, 024670).

Techniques: In Vivo, Expressing, Staining, Isolation, Two Tailed Test

Journal: Metabolism: clinical and experimental

Article Title: Serum Response Factor (SRF) promotes actin cytoskeletal organization in adipocytes to support adaptive hypertrophic expansion and tissue remodeling during obesity in mice

doi: 10.1016/j.metabol.2026.156548

Figure Lengend Snippet: Compromised structural integrity and increased cellular fragility in SRF-deficient adipocytes. (A) Basal and isoproterenol (ISO)-stimulated lipolysis, measured by glycerol release from 4-h eWAT and iWAT explants from WT and SRF-AKO male mice ( n = 3 per condition, total N = 12). (B) Representative transmission electron microscopy (TEM) images of eWAT from WT and SRF-AKO female mice, showing ruptured adipocyte membranes (indicated by black arrows). Scale bar: 5 μm. (C) Quantification of apoptotic cells in eWAT and iWAT from WT (eWAT, n = 3; iWAT, n = 5) and SRF-AKO (eWAT, n = 3; iWAT, n = 3) male mice by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining. (D) BODIPY staining of eWAT and iWAT from WT and SRF-AKO male mice following 1.5-h of compression. Scale bar: 100 μm. A two-tailed Student’s t -test was used for statistical analysis. * P < 0.05, ** P < 0.01.

Article Snippet: For generation of SRF knockout mice specific to beige and brown adipocytes (SRF-BKO), Srf -flox mice were crossed with Ucp1 -Cre mice (Jackson Laboratory, 024670).

Techniques: Transmission Assay, Electron Microscopy, TUNEL Assay, Staining, Two Tailed Test

Journal: Metabolism: clinical and experimental

Article Title: Serum Response Factor (SRF) promotes actin cytoskeletal organization in adipocytes to support adaptive hypertrophic expansion and tissue remodeling during obesity in mice

doi: 10.1016/j.metabol.2026.156548

Figure Lengend Snippet: Impaired vascular integrity and altered cell-cell communication in adipose tissue driven by loss of SRF in adipocytes. (A) UMAP visualization of 34,457 single nuclei isolated from eWAT and iWAT of WT and SRF-AKO male mice (total N = 4), with annotated cell types. (B) Violin plots of cell type-specific marker gene expression across all identified cell types. (C) Relative proportions of each cell type in eWAT and iWAT from WT and SRF-AKO male mice. (D–E) Whole-mount staining of eWAT from WT and SRF-AKO mice with Hoechst (blue), BODIPY (green), and either F4/80 (red, D) or PECAM1 (red, E). Scale bar: 100 μm. (F) Circle plots from CellChat analysis showing altered cell-cell communication in eWAT of SRF-AKO male mouse compared to WT. Increases in interaction number (left) and strength (right) are shown in red; decreases are shown in blue.

Article Snippet: For generation of SRF knockout mice specific to beige and brown adipocytes (SRF-BKO), Srf -flox mice were crossed with Ucp1 -Cre mice (Jackson Laboratory, 024670).

Techniques: Isolation, Marker, Gene Expression, Staining

Journal: Metabolism: clinical and experimental

Article Title: Serum Response Factor (SRF) promotes actin cytoskeletal organization in adipocytes to support adaptive hypertrophic expansion and tissue remodeling during obesity in mice

doi: 10.1016/j.metabol.2026.156548

Figure Lengend Snippet: Role of SRF in actin filament structure and cellular expansion in adipocytes in vivo during obesity. (A) Body weight trajectories of wild-type (WT, n = 11) and tamoxifen-inducible, adipocyte-specific Srf KO (SRF-AKO, n = 9) male mice during HFD feeding. Total N = 20. (B) Heatmap showing the relative expression of cytoskeletal and collagen genes in eWAT from WT ( n = 6) and SRF-AKO male mice ( n = 5). Total N = 11. (C) Phalloidin staining of actin filaments in isolated adipocytes from WT and SRF-AKO male mice (scale bar: 20 μm). (D–E) Co-staining of isolated adipocytes with phalloidin (red) and PLIN1 (green) from both eWAT and iWAT of female mice. Scale bar: 100 μm, with quantification of phalloidin signal intensity. (F–G) Representative H&E-stained adipose tissue sections from (F) eWAT and (G) iWAT of WT and SRF-AKO male mice, with quantification of average adipocyte size. Scale bar: 100 μm. A two-tailed Student’s t -test was used for statistical analysis. ** P < 0.01, *** P < 0.001, **** P < 0.0001.

Article Snippet: To generate inducible adipocyte-specific SRF knockout (SRF-AKO) mice, Srf -flox mice (Jackson Laboratory, 006658) were crossed with Adipoq -CreERT2 mice (Jackson Laboratory, 024671).

Techniques: In Vivo, Expressing, Staining, Isolation, Two Tailed Test

Journal: Metabolism: clinical and experimental

Article Title: Serum Response Factor (SRF) promotes actin cytoskeletal organization in adipocytes to support adaptive hypertrophic expansion and tissue remodeling during obesity in mice

doi: 10.1016/j.metabol.2026.156548

Figure Lengend Snippet: Impaired systemic glucose homeostasis and partial lipodystrophy phenotype in SRF-AKO mice during obesity. (A–C) Defective glucose homeostasis in SRF-AKO ( n = 9) compared to WT ( n = 11) male mice during obesity (total N = 20), assessed by (A) glucose tolerance test (GTT, 1 g/kg body weight glucose), (B) insulin tolerance test (ITT, 1 U/kg body weight insulin), and (C) fasting insulin levels (ng/mL) relative to body weight. (D) Tissue weight (% of body weight) of eWAT, iWAT, and BAT, and liver in WT ( n = 11) and SRF-AKO ( n = 9) male mice. Total N = 20. (E–F) Representative H&E-stained sections of (E) BAT and (F) liver from WT and SRF-AKO male mice. Scale bar: 100 μm. A two-tailed Student’s t -test was used for statistical analysis. * P < 0.05, ** P < 0.01.

Article Snippet: To generate inducible adipocyte-specific SRF knockout (SRF-AKO) mice, Srf -flox mice (Jackson Laboratory, 006658) were crossed with Adipoq -CreERT2 mice (Jackson Laboratory, 024671).

Techniques: Staining, Two Tailed Test

Journal: Metabolism: clinical and experimental

Article Title: Serum Response Factor (SRF) promotes actin cytoskeletal organization in adipocytes to support adaptive hypertrophic expansion and tissue remodeling during obesity in mice

doi: 10.1016/j.metabol.2026.156548

Figure Lengend Snippet: Compromised structural integrity and increased cellular fragility in SRF-deficient adipocytes. (A) Basal and isoproterenol (ISO)-stimulated lipolysis, measured by glycerol release from 4-h eWAT and iWAT explants from WT and SRF-AKO male mice ( n = 3 per condition, total N = 12). (B) Representative transmission electron microscopy (TEM) images of eWAT from WT and SRF-AKO female mice, showing ruptured adipocyte membranes (indicated by black arrows). Scale bar: 5 μm. (C) Quantification of apoptotic cells in eWAT and iWAT from WT (eWAT, n = 3; iWAT, n = 5) and SRF-AKO (eWAT, n = 3; iWAT, n = 3) male mice by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining. (D) BODIPY staining of eWAT and iWAT from WT and SRF-AKO male mice following 1.5-h of compression. Scale bar: 100 μm. A two-tailed Student’s t -test was used for statistical analysis. * P < 0.05, ** P < 0.01.

Article Snippet: To generate inducible adipocyte-specific SRF knockout (SRF-AKO) mice, Srf -flox mice (Jackson Laboratory, 006658) were crossed with Adipoq -CreERT2 mice (Jackson Laboratory, 024671).

Techniques: Transmission Assay, Electron Microscopy, TUNEL Assay, Staining, Two Tailed Test

Journal: Metabolism: clinical and experimental

Article Title: Serum Response Factor (SRF) promotes actin cytoskeletal organization in adipocytes to support adaptive hypertrophic expansion and tissue remodeling during obesity in mice

doi: 10.1016/j.metabol.2026.156548

Figure Lengend Snippet: Impaired vascular integrity and altered cell-cell communication in adipose tissue driven by loss of SRF in adipocytes. (A) UMAP visualization of 34,457 single nuclei isolated from eWAT and iWAT of WT and SRF-AKO male mice (total N = 4), with annotated cell types. (B) Violin plots of cell type-specific marker gene expression across all identified cell types. (C) Relative proportions of each cell type in eWAT and iWAT from WT and SRF-AKO male mice. (D–E) Whole-mount staining of eWAT from WT and SRF-AKO mice with Hoechst (blue), BODIPY (green), and either F4/80 (red, D) or PECAM1 (red, E). Scale bar: 100 μm. (F) Circle plots from CellChat analysis showing altered cell-cell communication in eWAT of SRF-AKO male mouse compared to WT. Increases in interaction number (left) and strength (right) are shown in red; decreases are shown in blue.

Article Snippet: To generate inducible adipocyte-specific SRF knockout (SRF-AKO) mice, Srf -flox mice (Jackson Laboratory, 006658) were crossed with Adipoq -CreERT2 mice (Jackson Laboratory, 024671).

Techniques: Isolation, Marker, Gene Expression, Staining