https://orcid.org/0000-0002-2460-4808
Figures & data
Figure 1. MT1-MMP ectopic expression in the brainstem abolishes the GDF15 action in vivo. The mice transduced with either AAV-MMP14 or AAV-control were sacrificed at around 2 weeks post-injection for analysis. (a) Immunostaining of GFRAL (green) in the brainstem of mice transduced with either AAV-MMP14 or AAV-control. The expression of ectopic MT1-MMP was visualized by the detection of mCherry signal (red). AP region limited with the white dashed lines. Scale bar 50 μm. (b) The bodyweight, (c) the change in bodyweight (d), cumulative 6-day food intake (e) and the percentage change in food intake in response to GDF15 treatment (10 nmol/kg) for 6 days in mice transduced with either AAV-MMP14 or AAV-control. (n = 4). Data are reported as average ± s.e.m. *P < 0.05; **P < 0.01; ***P < 0.001.
Figure 2. Diagram illustrating genetic ablation of MT1-MMP restores the GFRAL expression. Obesity induced MT1-MMP modulate protein levels of GFRAL in hindbrain neurons by proteolytic clipping it from the surface and inhibiting the GDF15 activity. Genetic ablation of MT1-MMP restores the GFRAL expression and potentiates the response to GDF15. Upregulation of GDF15-GFRAL signaling pathway prevented the diet induced obesity in mice by reducing the food intake and improving the glucose tolerance.
