Empagliflozin reduces podocyte lipotoxicity in experimental Alport syndrome

• DOI: 10.7554/elife.83353
• Publication Date: 2023-05-02T12:00:54Z
• Authors: Mengyuan Ge; Judith Molina; Jin-Ju Kim; Shamroop K Mallela; Anis Ahmad; Javier Varona Santos; Hassan Al-Ali; Alla Mitrofanova; Kumar Sharma; Flavia Fontanesi; Sandra Merscher; Alessia Fornoni
• Keywords: Empagliflozin; Lipotoxicity; Albuminuria

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are anti-hyperglycemic agents that prevent glucose reabsorption in proximal tubular cells. SGLT2i improves renal outcomes both diabetic and non-diabetic patients, indicating it may have beneficial effects beyond glycemic control. Here, we demonstrate affects energy metabolism podocyte lipotoxicity experimental Alport syndrome (AS). In vitro, found the SGLT2 protein was expressed human mouse podocytes to a similar extent Newly established immortalized from Col4a3 knockout mice (AS podocytes) accumulate lipid droplets along with increased apoptosis when compared wild-type podocytes. Treatment empagliflozin reduces droplet accumulation AS Empagliflozin inhibits utilization of glucose/pyruvate as metabolic substrate but not vivo, albuminuria prolongs survival mice. Empagliflozin-treated show decreased serum blood urea nitrogen creatinine levels association reduced triglyceride cholesterol ester content kidney cortices Lipid correlates decline function. summary, function substrates switch fatty acids