Journal: Diabetes, Metabolic Syndrome and Obesity

Article Title: Irisin Ameliorates Renal Tubulointerstitial Fibrosis by Regulating the Smad4/β-Catenin Pathway in Diabetic Mice

doi: 10.2147/dmso.s407734

Figure Lengend Snippet: Figure 2 Irisin may be involved in the progression of DKD through TGFBR2. (A) Expression of FNDC5 gene at mRNA level. (B) Expression of TGF-β1 gene at mRNA level. (C) Expression of TGFBR2 gene at mRNA level. (D) Red fluorescent-labeled TGFBR2 and green fluorescent-labeled irisin co-localized on the cell membrane of HK-2 cells grown in high glucose. Values are expressed as mean ± SD. **p < 0.01 vs healthy group, ***p < 0.001 vs healthy group.

Article Snippet: The plasmid overexpressing FNDC5 gene (NM-153756) was purchased from OriGene Technologies.

Techniques: Expressing, Labeling, Membrane

Journal: Diabetes, Metabolic Syndrome and Obesity

Article Title: Irisin Ameliorates Renal Tubulointerstitial Fibrosis by Regulating the Smad4/β-Catenin Pathway in Diabetic Mice

doi: 10.2147/dmso.s407734

Figure Lengend Snippet: Figure 5 Irisin restored changes in biochemical markers and renal function deterioration in diabetic mice. (A–C) After completing the FNDC5 overexpression plasmid therapy, the mice were put to death at 24 weeks and the animals were split up into the control, DM, DM+Vector, and DM+FNDC5 groups. Data on body weight, kidney weight, and the ratio of kidney weight/body weight were gathered. (D–F) 24 h urinary protein levels, Scr and TC were obtained from four different groups. (G) HE, PAS, and Masson trichrome staining in four sets of renal tissue sections are shown in example pathological images. Each experiment was carried out separately and at least three times. Values are expressed as mean ± SD. **p < 0.01 vs Control group, ***p < 0.001 vs Control group, #p< 0.05 vs DM group, ##p < 0.01 vs DM group.

Article Snippet: The plasmid overexpressing FNDC5 gene (NM-153756) was purchased from OriGene Technologies.

Techniques: Over Expression, Plasmid Preparation, Control, Staining

Journal: Frontiers in aging neuroscience

Article Title: PGC-1α or FNDC5 Is Involved in Modulating the Effects of Aβ 1-42 Oligomers on Suppressing the Expression of BDNF, a Beneficial Factor for Inhibiting Neuronal Apoptosis, Aβ Deposition and Cognitive Decline of APP/PS1 Tg Mice.

doi: 10.3389/fnagi.2017.00065

Figure Lengend Snippet: FIGURE 2 | The Aβ1−42 oligomers suppressed the expression of BDNF through a PGC-1α- and FNDC5-dependent mechanism. (A,B) The n2a cells were treated with Aβ oligomers (1 ng/ml) for 48 h. (C,D) In select experiments, the n2a cells were transfected with either PGC-1α or FNDC5 cDNA for 48 h. (E) In separate experiments, the n2a cells were transfected with either PGC-1α or FNDC5 cDNA before the treatment with Aβ oligomers for 48 h. The mRNA and protein levels of BDNF, PGC-1α and FNDC5 were determined by qRT-PCR and western blots, respectively. GAPDH and β-actin served as the internal controls. The data represent the means ± S.E. of three times experiments. *p < 0.05 compared with vehicle-treated or vector-transfected controls. #p < 0.05 compared with Aβ-treated alone.

Article Snippet: PGC1α or FNDC5 cDNA plasmids were obtained from Origene Technologies (Rockville, MD, USA) and subcloned into the pCMV6-XL vector.

Techniques: Expressing, Transfection, Quantitative RT-PCR, Western Blot, Plasmid Preparation

Journal: Frontiers in aging neuroscience

Article Title: PGC-1α or FNDC5 Is Involved in Modulating the Effects of Aβ 1-42 Oligomers on Suppressing the Expression of BDNF, a Beneficial Factor for Inhibiting Neuronal Apoptosis, Aβ Deposition and Cognitive Decline of APP/PS1 Tg Mice.

doi: 10.3389/fnagi.2017.00065

Figure Lengend Snippet: FIGURE 3 | Elevating the levels of PGC-1α, FNDC5 and BDNF partially protected neurons from Aβ1−42 oligomer-induced apoptosis. (A,B) The neurons were incubated with Aβ (1 ng/ml) in the absence or presence of transfection with either PGC-1α or FNDC5 cDNA. (C,D) In select experiments, the n2a cells were incubated with Aβ (1 ng/ml) in the absence or presence of BDNF (1 ng/ml). (A,C) The viability of neurons in different groups was determined by an MTT assay. (B,D) The apoptosis of neurons was determined by flow cytometry after staining with PI and annexin V. The data represent the means ± S. E. of three times experiments. *p < 0.05 compared with vehicle-treated or vector-transfected controls. #p < 0.05 compared with Aβ-treated alone.

Article Snippet: PGC1α or FNDC5 cDNA plasmids were obtained from Origene Technologies (Rockville, MD, USA) and subcloned into the pCMV6-XL vector.

Techniques: Incubation, Transfection, MTT Assay, Cytometry, Staining, Plasmid Preparation

Journal: Frontiers in aging neuroscience

Article Title: PGC-1α or FNDC5 Is Involved in Modulating the Effects of Aβ 1-42 Oligomers on Suppressing the Expression of BDNF, a Beneficial Factor for Inhibiting Neuronal Apoptosis, Aβ Deposition and Cognitive Decline of APP/PS1 Tg Mice.

doi: 10.3389/fnagi.2017.00065

Figure Lengend Snippet: FIGURE 5 | Signaling events involved in BDNF regulation during the course of AD development and the critical roles of BDNF in inhibiting the apoptosis of neurons, Aβ deposition and cognitive decline of the APP/PS1 Tg mice. BDNF expression was downregulated in the APP/PS1 Tg mice, and the Aβ1−42 oligomers are responsible for decreasing the expression of BDNF through a PGC-1α- and FNDC5-dependent mechanism. Reciprocally, elevating the levels of PGC-1α, FNDC5 and BDNF alleviated the effects of the Aβ1−42 oligomers on neuronal apoptosis. More importantly, BDNF treatment decreased the deposition of Aβ and reduced the cognitive decline of APP/PS1 Tg mice.

Article Snippet: PGC1α or FNDC5 cDNA plasmids were obtained from Origene Technologies (Rockville, MD, USA) and subcloned into the pCMV6-XL vector.

Techniques: Expressing

Journal: Iranian Journal of Basic Medical Sciences

Article Title: Irisin attenuates angiotensin II-induced atrial fibrillation and atrial fibrosis via LOXL2 and TGFβ1/Smad2/3 signaling pathways

doi: 10.22038/IJBMS.2023.68639.14967

Figure Lengend Snippet: Irisin expression is decreased in Ang II-induced mice and increased by aerobic exercise. Mice were infused with saline or Ang II (2000 ng/kg/min) using osmotic mini-pumps for four weeks or kept in a sedentary state and subjected to aerobic exercise for four weeks. (a) Irisin protein levels in serum are significantly reduced in Ang-II-induced compared with control mice and are significantly increased in mice with aerobic exercise compared with sedentary mice. (b) mRNA levels of irisin precursor FNDC5 are determined in the atria muscle by RT-qPCR. (c) Representative bands of FNDC5 protein in atria muscle of mice by western blot. (d) Quantification of FNDC5 protein levels. Data are presented as mean ± SD (n=8 in each group). *** P <0.001 vs saline group; ### P <0.001 vs sedentary group

Article Snippet: With 5% skimmed milk, the membranes were blocked and incubated with primary and secondary antibodies against LOXL2 (1:500, sc-293427, mouse monoclonal, Santa Cruz); FNDC5 (1:1000, ab131390), Collagen I (1:500, ab255809), Collagen III (1:500, ab7778), TGF-β1( 1:1000; ab179695), p-Smad2 (1:500, ab188334), p-Smad3 (1:500, ab52903), Smad2/3 (1:1000, ab202445), and GAPDH (1:1000, ab9485) (Abcam, Cambridge, UK).

Techniques: Expressing, Saline, Control, Quantitative RT-PCR, Western Blot

Journal: Cell Death Discovery

Article Title: Irisin inhibits adipogenic differentiation of bone marrow mesenchymal stem cells through the SIRT1/RANBP2/FTO signaling axis and protects against osteoporosis

doi: 10.1038/s41420-026-02976-5

Figure Lengend Snippet: A Schematic workflow of the RNA-seq. B Volcanic maps of RNA-Seq during adipogenic differentiation in BMMSCs. C Heatmap of mRNA expression during adipogenic differentiation, with high and low expression levels shown in red and blue, respectively. D Structure of FNDC5 and irisin. E Schematic diagram of the OVX modeling workflow. F Representative micro-CT images of trabecular bone from the femoral metaphysis in sham and OVX mice. Cortical bone volume/total volume (Ct. BV/TV), trabecular bone volume/total volume (Tb. BV/TV), trabecular thickness (Tb. Th), cortical thickness (Ct. Th), and number of trabeculae (Tb. N), and trabecular separation (Tb. Sp) analysis of the femurs in sham and OVX mice. G Representative images of H&E staining in sham and OVX mice. H Representative images of Masson staining in sham and OVX mice. I Representative images of immunohistochemistry staining for FNDC5 in sham and OVX mice. J FNDC5 expression in bone tissue was detected by western blotting in the Sham and OVX mice. K The serum concentration of CTX-1 and irisin was detected by ELISA in the sham and OVX mice. L The serum concentration of CTX-1 and irisin was detected by ELISA in the control group and osteoporosis group. The values are mean ± SD of at least three independent experiments; n.s. p > 0.05, * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001.

Article Snippet: In brief, equal amounts of protein samples were separated on polyacrylamide gels and transferred to nitrocellulose membranes, which were closed for 1 h using 5% skimmed milk powder, and the membranes obtained were incubated with anti-FNDC5 antibody (#23995-1-AP, 1:1000, Proteintech, China), anti-PPARγ antibody (#7273, 1:1000, Santa Cruz Biotechnology, USA), anti-C/EBPα antibody (#2295, 1:1000, Cell Signaling Technology, USA), anti-C/EBPβ antibody (#3087, 1:1000, Cell Signaling Technology, USA), anti-SIRT1 antibody (#8469, 1:1000, Cell Signaling Technology, USA), anti-FTO antibody (#27226-1-AP, Proteintech, China), anti-RANBP2 antibody (#ab315458, 1:1000, Abcam, USA), and anti-GAPDH antibody (#10494-1, 1:1000, proteintech, China) were incubated at 4 °C overnight.

Techniques: RNA Sequencing, Expressing, Micro-CT, Staining, Immunohistochemistry, Western Blot, Concentration Assay, Enzyme-linked Immunosorbent Assay, Control

Journal: Redox biology

Article Title: Muscle-derived factor alleviated cognitive impairment caused by intestinal ischemia-reperfusion.

doi: 10.1016/j.redox.2025.103682

Figure Lengend Snippet: Fig. 4. Knockout of FNDC5/irisin exacerbates brain injury following II/R. (A) Schematic representation of FNDC5 cleavage to generate irisin. (B) Representative WB bands showing FNDC5 levels at different time points post-II/R injury and β-actin was used as loading control. (C) Relative levels of FNDC5 (Data are presented as mean ± SD; n = 6; **P < 0.01 vs. Sham group). (D) Schematic diagram of the Fndc5 gene knockout locus. (E) Representative WB bands confirming the loss of FNDC5 and irisin relative levels after FNDC5 knockout, β-actin was used as loading control, FNDC5 and irisin correspond to separate loading controls. (F) Relative levels of FNDC5 and irisin (Data are presented as mean ± SD; n = 6; **P < 0.01 vs. WT group). (G) Representative H&E staining of the CA1 region of the hippocampus in Fndc5 knockout mice at 48 h post-II/R injury (n = 6, scale bars = 50 μm). (H) Quantification of normal neurons in the CA1 region of the hippocampus (Data are presented as mean ± SD; n = 6; **P < 0.01 vs. WT-Sham group; ##P < 0.01 vs. KO-Sham group; &P < 0.05 vs. WT-II/R group). (I–K) MWM test results, including escape latency, time spent in the target quadrant, and platform crossings (n = 8; Data are presented as mean ± SD; *P < 0.05, **P < 0.01 vs. WT-Sham group; ##P < 0.01 vs. KO-Sham group; &P < 0.05 vs. WT-II/R group). (L) concentration of inflammatory cytokines in plasma and hippocampal tissue (Data are presented as mean ± SD; n = 8; **P < 0.01 vs. WT-Sham group; ##P < 0.01 vs. KO-Sham group; &P < 0.05, &&P < 0.01 vs. WT-II/R group).

Article Snippet: Fndc5 − /− mice on a C57BL/6 background were obtained with CRISPR/Cas9 technology from Cyagen Biosciences Co., Ltd (Guangzhou, China).

Techniques: Knock-Out, Control, Gene Knockout, Staining, Concentration Assay, Clinical Proteomics

Journal: Redox biology

Article Title: Muscle-derived factor alleviated cognitive impairment caused by intestinal ischemia-reperfusion.

doi: 10.1016/j.redox.2025.103682

Figure Lengend Snippet: Fig. 5. Irisin inhibits the inflammatory activation pathway in brain injury following II/R in mice. (A) Representative TEM images of hippocampal tissue (Red arrows indicate mitochondrial alterations within the different groups. Scale bar = 1 μm). (B) Quantification of indicators related to lipid peroxidation concentrations in the hippocampus after irisin treatment following II/R injury (n = 8; Data are presented as mean ± SD; **P < 0.01 vs. Sham group; #P < 0.05, ##P < 0.01 vs. Veh group). (C) Representative WB bands showing the levels of apoptosis-related molecules in the hippocampus after irisin treatment in II/R mice. β-actin was used as loading control and Bcl-2, Bax and Cl-caspase 3 correspond to a same loading controls (D) Relative levels of apoptosis-related molecules in the hippocampus (n = 6; Data are presented as mean ± SD; **P < 0.01 vs. Sham group; #P < 0.05 vs. Veh group). (E) Schematic diagram illustrating inflammasome assembly and activation. (F) Representative WB bands of FNDC5, TXNIP, NLRP3, Pro-caspase-1, and Cleaved caspase-1 in the hippocampus at different time points after II/R injury, -β-actin was used as loading control and all were referred to the same loading control. (G) Relative levels of FNDC5, TXNIP, NLRP3, Pro-caspase-1, and Cleaved caspase-1 in the hippocampus (n = 6; Data are presented as mean ± SD; *P < 0.05, **P < 0.01, ***P < 0.001 vs. Sham group).

Article Snippet: Fndc5 − /− mice on a C57BL/6 background were obtained with CRISPR/Cas9 technology from Cyagen Biosciences Co., Ltd (Guangzhou, China).

Techniques: Activation Assay, Control

Journal: Redox biology

Article Title: Muscle-derived factor alleviated cognitive impairment caused by intestinal ischemia-reperfusion.

doi: 10.1016/j.redox.2025.103682

Figure Lengend Snippet: Fig. 6. Interaction analysis of irisin with TXNIP and NLRP3 respectively. (A) Schematic diagram illustrating the TXNIP-NLRP3 axis. (B) Molecular interaction model of TXNIP with FNDC5/irisin. (C) Molecular interaction model of NLRP3 with FNDC5/irisin. (D) Co-IP representative bands for irisin and TXNIP interaction analysis. (E) Co-IP representative bands for irisin and NLRP3 interaction analysis.

Article Snippet: Fndc5 − /− mice on a C57BL/6 background were obtained with CRISPR/Cas9 technology from Cyagen Biosciences Co., Ltd (Guangzhou, China).

Techniques: Co-Immunoprecipitation Assay

Journal: Redox biology

Article Title: Muscle-derived factor alleviated cognitive impairment caused by intestinal ischemia-reperfusion.

doi: 10.1016/j.redox.2025.103682

Figure Lengend Snippet: Fig. 7. Irisin targets TXNIP to mitigate neuronal apoptosis in the hippocampus of II/R mice. (A) Representative WB bands of FNDC5, TXNIP, NLRP3, Pro-caspase-1, and Cleaved caspase-1 in the hippocampus of II/R mice after irisin treatment, β-actin was used as loading control and all were referred to the same loading control. (B) Relative levels of FNDC5, TXNIP, NLRP3, Pro-caspase-1, and Cleaved caspase-1 in the hippocampus (n = 6; Data are presented as mean ± SD; **P < 0.01 vs. Sham group; #P < 0.05, ##P < 0.01 vs. Veh group). (C) Concentrations of inflammatory cytokines in plasma and hippocampal tissue (n = 8; Data are presented as mean ± SD; **P < 0.01 vs. Sham group; ##P < 0.01 vs. Veh group). (D) Representative WB bands of FNDC5, TXNIP, NLRP3, Pro-caspase-1, and Cleaved caspase-1 in the hippocampus of Fndc5-knockout II/R mice, β-actin was used as loading control and all were referred to the same loading control. (E) Representative WB bands of apoptosis-related molecules in the hippocampus of Fndc5-knockout II/R mice, β-actin was used as loading control and all were referred to the same loading control. (F) Relative levels of FNDC5, TXNIP, NLRP3, Pro-caspase-1, and Cleaved caspase-1 in the hippocampus (Data are presented as mean ± SD; n = 6; *P < 0.05, **P < 0.01 vs. WT-Sham group; ##P < 0.01 vs. KO-Sham group; &P < 0.05 vs. WT-II/R group). (G) Relative levels of apoptosis-related molecules in the hippocampus (Data are presented as mean ± SD; n = 6; *P < 0.05 vs. WT-Sham group; ##P < 0.01 vs. KO-Sham group; &P < 0.05, &&P < 0.01 vs. WT-II/R group). (H) Representative TUNEL staining images showing apoptotic neurons in the CA1 region of the hippocampus after FNDC5 knockout (Scale bar = 20 μm). (I) Quantification of the relative fluorescence intensity of TUNEL-positive cells in the CA1 region of the hippocampus (Data are presented as mean ± SD; n = 6; **P < 0.01 vs. WT-Sham group; ##P < 0.01 vs. KO-Sham group; &&P < 0.01 vs. WT-II/R group).

Article Snippet: Fndc5 − /− mice on a C57BL/6 background were obtained with CRISPR/Cas9 technology from Cyagen Biosciences Co., Ltd (Guangzhou, China).

Techniques: Control, Clinical Proteomics, Knock-Out, TUNEL Assay, Staining, Fluorescence

Journal: Redox biology

Article Title: Muscle-derived factor alleviated cognitive impairment caused by intestinal ischemia-reperfusion.

doi: 10.1016/j.redox.2025.103682

Figure Lengend Snippet: Fig. 9. Irisin modulates microglial polarization by targeting TXNIP in microglia. (A) Representative WB bands and relative levels of iNOS and Arg-1 in the hip pocampus of II/R mice after irisin treatment (β-actin was used as loading control and all were referred to the same loading control, n = 6. Data are presented as mean ± SD; *P < 0.05, **P < 0.01 vs. Sham group; #P < 0.05, ##P < 0.01 vs. Veh group). (B) Representative WB bands and relative levels of iNOS and Arg-1 in the hippocampus of Fndc5-knockout II/R mice (β-actin was used as loading control and all were referred to the same loading control. Data are presented as mean ± SD; n = 6; *P < 0.05 vs. WT-Sham group; ##P < 0.01 vs. KO-Sham group; &P < 0.05, &&P < 0.01 vs. WT-II/R group). (C–D) Representative images showing the levels of M1 microglial marker CD16 and M2 microglial marker CD206 in the hippocampus (Scale bar = 20 μm). (E) Relative levels of CD16+ microglia and CD206+ microglia in the hippocampus (n = 6; Data are presented as mean ± SD; **P < 0.01 vs. Sham group; ##P < 0.01 vs. Veh group). (F) Representative images of TXNIP co-localized with Iba-1 in the hippocampus after irisin treatment (Scale bar = 20 μm). (G) Relative fluorescence intensity of TXNIP level in the hippocampus (n = 6; Data are presented as mean ± SD; **P < 0.01 vs. Sham group; ##P < 0.01 vs. Veh group).

Article Snippet: Fndc5 − /− mice on a C57BL/6 background were obtained with CRISPR/Cas9 technology from Cyagen Biosciences Co., Ltd (Guangzhou, China).

Techniques: Control, Knock-Out, Marker, Fluorescence

Journal: Redox biology

Article Title: Muscle-derived factor alleviated cognitive impairment caused by intestinal ischemia-reperfusion.

doi: 10.1016/j.redox.2025.103682

Figure Lengend Snippet: Fig. 12. Schematic diagram depicting the mechanisms by which FNDC5/irisin–mediated microglial anti-inflammatory phenotype polarization, and further improved II/R-mediated brain injure and cognitive deficits via the TXNIP. TXNIP facilitates the interaction between FNDC5/irisin and microglia, which promotes the microglial anti-inflammation phenotype polarization, thus suppressing pro-inflammation phenotype polarization, resulting in the improvement of cognitive deficits and the inhibition of oxidative stress, neuroinflammation, and neuronal loss after II/R.

Article Snippet: Fndc5 − /− mice on a C57BL/6 background were obtained with CRISPR/Cas9 technology from Cyagen Biosciences Co., Ltd (Guangzhou, China).

Techniques: Inhibition