A metabonomics-based renoprotective mechanism analysis of empagliflozin in obese mice
Abstract
With an increasing prevalence of obesity related kidney disease, exploring the mechanisms of therapeutic method is of critical importance. Empagliflozin is a new antidiabetic agent with broad clinical application prospect in cardiovascular and renal diseases. However, a metabonomics-based renoprotective mechanism of empagliflozin in obesity remains unclear. Our results showed that empagliflozin significantly alleviated the deposition of lipid droplet, glomerular and tubular injury. The innovation lied in detection of empagliflozin-targeted differential metabolites in kidneys. Compared with normal control mice, obese mice showed higher levels of All-trans-heptaprenyl diphosphate, Biliverdin, Galabiose, Galabiosylceramide (d18:1/16:0), Inosine, Methylisocitric acid, Uric acid, Xanthosine, O-glutarylcarnitine, PG(20:3(8Z,11Z,14Z)/0:0), PG(20:4(5Z,8Z,11Z,14Z)/0:0), PE(O-16:0/0:0), PG(22:6(4Z,7Z,10Z,13Z,16Z,19Z)/0:0), and lower level of Adenosine. Empagliflozin regulated these metabolites in the opposite direction. Associated metabolic pathways were Phospholipids metabolism, Purine metabolism, and Biliverdin metabolism. Most of metabolites were associated with inflammatory response and oxidative stress. Empagliflozin improved the oxidative stress and inflammation imbalance. Our study revealed the metabonomics-based renoprotective mechanism of empagliflozin in obese mice for the first time. Empagliflozin may be a promising tool to delay the progression of obesity-related kidney…
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