Abstract
Obesity is supposed to cause renal injury via autophagy deficiency. Recently, sodium glucose co-transporter 2 inhibitors (SGLT2i) were reported to protect renal injury. However, the mechanisms of SGLT2i for renal protection are unclear. Here, we investigated the effect of SGLT2i for autophagy in renal proximal tubular cells (PTCs) on obesity mice. We fed C57BL/6J mice with a normal diet (ND) or high-fat and -sugar diet (HFSD) for nine weeks, then administered SGLT2i, empagliflozin, or control compound for one week. Each group contained N = 5. The urinary N-acetyl-beta-d-glucosaminidase level in the HFSD group significantly increased compared to ND group. The tubular damage was suppressed in the SGLT2i–HFSD group. In electron microscopic analysis, multi lamellar bodies that increased in autophagy deficiency were increased in PTCs in the HFSD group but significantly suppressed in the SGLT2i group. The autophagosomes of damaged mitochondria in PTCs in the HFSD group frequently appeared in the SGLT2i group. p62 accumulations in PTCs were significantly increased in HFSD group but significantly suppressed by SGLT2i. In addition, the mammalian target of rapamycin was activated in the HFSD group but significantly suppressed in SGLT2i group. These data suggest that SGLT2i has renal protective effects against obesity via improving autophagy flux impairment in PTCs on a HFSD.
Highlights
Much attention was focused on the associations between obesity/metabolic syndrome (MetS) and kidney injury recently
We found that sodium glucose co-transporter 2 inhibitor (SGLT2i) has a therapeutic effect on autophagy flux impairment in proximal tubular cells (PTCs) on obesity mice
These findings might contribute to elucidating the renal protective mechanism of SGLT2i in obesity patients
Summary
Much attention was focused on the associations between obesity/metabolic syndrome (MetS) and kidney injury recently. Many researches were conducted on the mechanisms of kidney injury by obesity/MetS. Autophagy deficiency is reported to be one of the renal injury causes [2]. Autophagy deficiency is observed in renal proximal tubular cells (PTCs) of obesity patients [2]. Autophagy flux impairment by lysosomal dysfunction, inflammasome activation, and macrophage invasion was observed in PTCs of obesity mice [3]. Autophagy deficiency is believed to be involved in kidney injury by obesity/MetS. MTCol.sScai.n2d02, 0t,h21e,r4e0f5o4re, lowering blood sugar, was reported to have renal protective effe2ctosf 1i4n chronic kidney disease patients [4]. We investigated the therapeutic e2ff.eRcet souflStsGLT2i on autophagy deficiency in PTCs of obesity mice.
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