Dapagliflozin elevates plasma high-density lipoprotein levels and influences visceral fat gene expression in streptozotocin-induced diabetes mellitus.

Abstract

Dapagliflozin (Dapa) could potentially be used to treat type 1 diabetes mellitus. We tested the hypothesis that it would influence blood lipid levels and visceral fat accumulation in a rodent diabetic model. We used three groups of male Wistar rats: Controls, streptozotocin (STZ)-treated rats and STZ-treated orally with Dapa (STZ+Dapa), 10 mg/kg/day for six weeks. Blood glucose and serum lipids levels were determined. Plasma levels of lipases (hormone-sensitive lipase, HSL and lipoprotein lipase, LPL), adipokines (leptin and adiponectin) and proinflammatory cytokines [tumour necrosis factor-alpha (TNFα) and interleukin-6 (IL-6)] were determined by ELISA assays. mRNA levels in the perirenal fat were determined by real-time PCR. Dapa suppressed STZ-related hyperglycemia by 20% (P < 0.05) and increased serum HDL when compared to the controls and the STZ-only treated rats (both P < 0.05). STZ treatment caused elevations of other serum lipids that were resistant to Dapa treatment. Dapa treatment also increased both plasma and visceral fat mRNA levels of leptin, LPL and IL-6, while decreasing plasma and fat expressions of HSL and TNFα compared to the STZ-only treated rats (all P < 0.05). Our results suggest that Dapa, in addition to its antidiabetic effect, also influences the function of adipose tissue which could be beneficial in the treatment of diabetes.