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<t>Elevated</t> <t>acetyl-CoA</t> levels exacerbate UC by promoting STAT3 acetylation. (A) Schematic representation of the experimental model. WT mice (n = 6) were gavaged with acetate (500 mg/kg) or PBS for 3 weeks, followed by treatment with metformin (200 mg/kg) and 3 % DSS for 7 days. (B) Relative acetyl-CoA levels in mice. (C-D) Representative IF images of ac-STAT3 K685 and IHC images of p-STAT3 Y705 in mice. (E) Alterations in body weight and DAI. (F-G) Gross morphology and colon length measurements in mice. (H) Representative images of H&E staining for morphological analysis and IHC analysis of AB-PAS and MUC-2 expression. (I) Histological evaluation of colonic tissue based on morphological examination of colon sections. (J-K) Representative immunofluorescence images of ZO-1 and TUNEL staining, along with quantitative analysis. (L) Representative electron microscopy images of colonic tissue segments. (M) WB analysis of colonic protein expression in mice. (N) ELISA analysis of relative intracellular acetyl-CoA levels (n = 3). NCM460 cells were exposed to acetate (5 mM) or PBS for 24 h, followed by treatment with metformin and LPS. (O) WB analysis of relevant protein expression in cells treated with acetate or PBS. (P-R) Representative immunofluorescence images of ZO-1, p-STAT3Y 705 , and ac-STAT3 K685 in cells.
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<t>Elevated</t> <t>acetyl-CoA</t> levels exacerbate UC by promoting STAT3 acetylation. (A) Schematic representation of the experimental model. WT mice (n = 6) were gavaged with acetate (500 mg/kg) or PBS for 3 weeks, followed by treatment with metformin (200 mg/kg) and 3 % DSS for 7 days. (B) Relative acetyl-CoA levels in mice. (C-D) Representative IF images of ac-STAT3 K685 and IHC images of p-STAT3 Y705 in mice. (E) Alterations in body weight and DAI. (F-G) Gross morphology and colon length measurements in mice. (H) Representative images of H&E staining for morphological analysis and IHC analysis of AB-PAS and MUC-2 expression. (I) Histological evaluation of colonic tissue based on morphological examination of colon sections. (J-K) Representative immunofluorescence images of ZO-1 and TUNEL staining, along with quantitative analysis. (L) Representative electron microscopy images of colonic tissue segments. (M) WB analysis of colonic protein expression in mice. (N) ELISA analysis of relative intracellular acetyl-CoA levels (n = 3). NCM460 cells were exposed to acetate (5 mM) or PBS for 24 h, followed by treatment with metformin and LPS. (O) WB analysis of relevant protein expression in cells treated with acetate or PBS. (P-R) Representative immunofluorescence images of ZO-1, p-STAT3Y 705 , and ac-STAT3 K685 in cells.
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<t>Elevated</t> <t>acetyl-CoA</t> levels exacerbate UC by promoting STAT3 acetylation. (A) Schematic representation of the experimental model. WT mice (n = 6) were gavaged with acetate (500 mg/kg) or PBS for 3 weeks, followed by treatment with metformin (200 mg/kg) and 3 % DSS for 7 days. (B) Relative acetyl-CoA levels in mice. (C-D) Representative IF images of ac-STAT3 K685 and IHC images of p-STAT3 Y705 in mice. (E) Alterations in body weight and DAI. (F-G) Gross morphology and colon length measurements in mice. (H) Representative images of H&E staining for morphological analysis and IHC analysis of AB-PAS and MUC-2 expression. (I) Histological evaluation of colonic tissue based on morphological examination of colon sections. (J-K) Representative immunofluorescence images of ZO-1 and TUNEL staining, along with quantitative analysis. (L) Representative electron microscopy images of colonic tissue segments. (M) WB analysis of colonic protein expression in mice. (N) ELISA analysis of relative intracellular acetyl-CoA levels (n = 3). NCM460 cells were exposed to acetate (5 mM) or PBS for 24 h, followed by treatment with metformin and LPS. (O) WB analysis of relevant protein expression in cells treated with acetate or PBS. (P-R) Representative immunofluorescence images of ZO-1, p-STAT3Y 705 , and ac-STAT3 K685 in cells.
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<t>Elevated</t> <t>acetyl-CoA</t> levels exacerbate UC by promoting STAT3 acetylation. (A) Schematic representation of the experimental model. WT mice (n = 6) were gavaged with acetate (500 mg/kg) or PBS for 3 weeks, followed by treatment with metformin (200 mg/kg) and 3 % DSS for 7 days. (B) Relative acetyl-CoA levels in mice. (C-D) Representative IF images of ac-STAT3 K685 and IHC images of p-STAT3 Y705 in mice. (E) Alterations in body weight and DAI. (F-G) Gross morphology and colon length measurements in mice. (H) Representative images of H&E staining for morphological analysis and IHC analysis of AB-PAS and MUC-2 expression. (I) Histological evaluation of colonic tissue based on morphological examination of colon sections. (J-K) Representative immunofluorescence images of ZO-1 and TUNEL staining, along with quantitative analysis. (L) Representative electron microscopy images of colonic tissue segments. (M) WB analysis of colonic protein expression in mice. (N) ELISA analysis of relative intracellular acetyl-CoA levels (n = 3). NCM460 cells were exposed to acetate (5 mM) or PBS for 24 h, followed by treatment with metformin and LPS. (O) WB analysis of relevant protein expression in cells treated with acetate or PBS. (P-R) Representative immunofluorescence images of ZO-1, p-STAT3Y 705 , and ac-STAT3 K685 in cells.
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<t>Elevated</t> <t>acetyl-CoA</t> levels exacerbate UC by promoting STAT3 acetylation. (A) Schematic representation of the experimental model. WT mice (n = 6) were gavaged with acetate (500 mg/kg) or PBS for 3 weeks, followed by treatment with metformin (200 mg/kg) and 3 % DSS for 7 days. (B) Relative acetyl-CoA levels in mice. (C-D) Representative IF images of ac-STAT3 K685 and IHC images of p-STAT3 Y705 in mice. (E) Alterations in body weight and DAI. (F-G) Gross morphology and colon length measurements in mice. (H) Representative images of H&E staining for morphological analysis and IHC analysis of AB-PAS and MUC-2 expression. (I) Histological evaluation of colonic tissue based on morphological examination of colon sections. (J-K) Representative immunofluorescence images of ZO-1 and TUNEL staining, along with quantitative analysis. (L) Representative electron microscopy images of colonic tissue segments. (M) WB analysis of colonic protein expression in mice. (N) ELISA analysis of relative intracellular acetyl-CoA levels (n = 3). NCM460 cells were exposed to acetate (5 mM) or PBS for 24 h, followed by treatment with metformin and LPS. (O) WB analysis of relevant protein expression in cells treated with acetate or PBS. (P-R) Representative immunofluorescence images of ZO-1, p-STAT3Y 705 , and ac-STAT3 K685 in cells.
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<t>Elevated</t> <t>acetyl-CoA</t> levels exacerbate UC by promoting STAT3 acetylation. (A) Schematic representation of the experimental model. WT mice (n = 6) were gavaged with acetate (500 mg/kg) or PBS for 3 weeks, followed by treatment with metformin (200 mg/kg) and 3 % DSS for 7 days. (B) Relative acetyl-CoA levels in mice. (C-D) Representative IF images of ac-STAT3 K685 and IHC images of p-STAT3 Y705 in mice. (E) Alterations in body weight and DAI. (F-G) Gross morphology and colon length measurements in mice. (H) Representative images of H&E staining for morphological analysis and IHC analysis of AB-PAS and MUC-2 expression. (I) Histological evaluation of colonic tissue based on morphological examination of colon sections. (J-K) Representative immunofluorescence images of ZO-1 and TUNEL staining, along with quantitative analysis. (L) Representative electron microscopy images of colonic tissue segments. (M) WB analysis of colonic protein expression in mice. (N) ELISA analysis of relative intracellular acetyl-CoA levels (n = 3). NCM460 cells were exposed to acetate (5 mM) or PBS for 24 h, followed by treatment with metformin and LPS. (O) WB analysis of relevant protein expression in cells treated with acetate or PBS. (P-R) Representative immunofluorescence images of ZO-1, p-STAT3Y 705 , and ac-STAT3 K685 in cells.
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<t>Elevated</t> <t>acetyl-CoA</t> levels exacerbate UC by promoting STAT3 acetylation. (A) Schematic representation of the experimental model. WT mice (n = 6) were gavaged with acetate (500 mg/kg) or PBS for 3 weeks, followed by treatment with metformin (200 mg/kg) and 3 % DSS for 7 days. (B) Relative acetyl-CoA levels in mice. (C-D) Representative IF images of ac-STAT3 K685 and IHC images of p-STAT3 Y705 in mice. (E) Alterations in body weight and DAI. (F-G) Gross morphology and colon length measurements in mice. (H) Representative images of H&E staining for morphological analysis and IHC analysis of AB-PAS and MUC-2 expression. (I) Histological evaluation of colonic tissue based on morphological examination of colon sections. (J-K) Representative immunofluorescence images of ZO-1 and TUNEL staining, along with quantitative analysis. (L) Representative electron microscopy images of colonic tissue segments. (M) WB analysis of colonic protein expression in mice. (N) ELISA analysis of relative intracellular acetyl-CoA levels (n = 3). NCM460 cells were exposed to acetate (5 mM) or PBS for 24 h, followed by treatment with metformin and LPS. (O) WB analysis of relevant protein expression in cells treated with acetate or PBS. (P-R) Representative immunofluorescence images of ZO-1, p-STAT3Y 705 , and ac-STAT3 K685 in cells.
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Elevated acetyl-CoA levels exacerbate UC by promoting STAT3 acetylation. (A) Schematic representation of the experimental model. WT mice (n = 6) were gavaged with acetate (500 mg/kg) or PBS for 3 weeks, followed by treatment with metformin (200 mg/kg) and 3 % DSS for 7 days. (B) Relative acetyl-CoA levels in mice. (C-D) Representative IF images of ac-STAT3 K685 and IHC images of p-STAT3 Y705 in mice. (E) Alterations in body weight and DAI. (F-G) Gross morphology and colon length measurements in mice. (H) Representative images of H&E staining for morphological analysis and IHC analysis of AB-PAS and MUC-2 expression. (I) Histological evaluation of colonic tissue based on morphological examination of colon sections. (J-K) Representative immunofluorescence images of ZO-1 and TUNEL staining, along with quantitative analysis. (L) Representative electron microscopy images of colonic tissue segments. (M) WB analysis of colonic protein expression in mice. (N) ELISA analysis of relative intracellular acetyl-CoA levels (n = 3). NCM460 cells were exposed to acetate (5 mM) or PBS for 24 h, followed by treatment with metformin and LPS. (O) WB analysis of relevant protein expression in cells treated with acetate or PBS. (P-R) Representative immunofluorescence images of ZO-1, p-STAT3Y 705 , and ac-STAT3 K685 in cells.

Journal: Journal of Advanced Research

Article Title: Metformin attenuates colitis via blocking STAT3 acetylation by reducing acetyl-CoA production

doi: 10.1016/j.jare.2025.03.058

Figure Lengend Snippet: Elevated acetyl-CoA levels exacerbate UC by promoting STAT3 acetylation. (A) Schematic representation of the experimental model. WT mice (n = 6) were gavaged with acetate (500 mg/kg) or PBS for 3 weeks, followed by treatment with metformin (200 mg/kg) and 3 % DSS for 7 days. (B) Relative acetyl-CoA levels in mice. (C-D) Representative IF images of ac-STAT3 K685 and IHC images of p-STAT3 Y705 in mice. (E) Alterations in body weight and DAI. (F-G) Gross morphology and colon length measurements in mice. (H) Representative images of H&E staining for morphological analysis and IHC analysis of AB-PAS and MUC-2 expression. (I) Histological evaluation of colonic tissue based on morphological examination of colon sections. (J-K) Representative immunofluorescence images of ZO-1 and TUNEL staining, along with quantitative analysis. (L) Representative electron microscopy images of colonic tissue segments. (M) WB analysis of colonic protein expression in mice. (N) ELISA analysis of relative intracellular acetyl-CoA levels (n = 3). NCM460 cells were exposed to acetate (5 mM) or PBS for 24 h, followed by treatment with metformin and LPS. (O) WB analysis of relevant protein expression in cells treated with acetate or PBS. (P-R) Representative immunofluorescence images of ZO-1, p-STAT3Y 705 , and ac-STAT3 K685 in cells.

Article Snippet: In a separate experiment, to reduce acetyl-CoA levels, NCM460 cells were exposed to ETC-1002 (10 μM for 12 h, Med Chem Express, #HY-12357), metformin or DMSO, followed by stimulation with LPS.

Techniques: Staining, Expressing, Immunofluorescence, TUNEL Assay, Electron Microscopy, Enzyme-linked Immunosorbent Assay