| First Author | Tsuruta H | Year | 2024 |
| Journal | Biochim Biophys Acta Mol Basis Dis | Volume | 1870 |
| Issue | 4 | Pages | 167074 |
| PubMed ID | 38354758 | Mgi Jnum | J:345719 |
| Mgi Id | MGI:7609699 | Doi | 10.1016/j.bbadis.2024.167074 |
| Citation | Tsuruta H, et al. (2024) Fructose overconsumption accelerates renal dysfunction with aberrant glomerular endothelial-mesangial cell interactions in db/db mice. Biochim Biophys Acta Mol Basis Dis 1870(4):167074 |
| abstractText | For the advancement of DKD treatment, identifying unrecognized residual risk factors is essential. We explored the impact of obesity diversity derived from different carbohydrate qualities, with an emphasis on the increasing trend of excessive fructose consumption and its effect on DKD progression. In this study, we utilized db/db mice to establish a novel diabetic model characterized by fructose overconsumption, aiming to uncover the underlying mechanisms of renal damage. Compared to the control diet group, the fructose-fed db/db mice exhibited more pronounced obesity yet demonstrated milder glucose intolerance. Plasma cystatin C levels were elevated in the fructose model compared to the control, and this elevation was accompanied by enhanced glomerular sclerosis, even though albuminuria levels and tubular lesions were comparable. Single-cell RNA sequencing of the whole kidney highlighted an increase in Lrg1 in glomerular endothelial cells (GECs) in the fructose model, which appeared to drive mesangial fibrosis through enhanced TGF-beta1 signaling. Our findings suggest that excessive fructose intake exacerbates diabetic kidney disease progression, mediated by aberrant Lrg1-driven crosstalk between GECs and mesangial cells. |
