Dapagliflozin Elevates Plasma High-Density Lipoprotein Levels And Influences Visceral Fat Gene Expression In Streptozotocin-Induced Diabetes Mellitus

Objectives 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.Methods 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 cyto-kines [tumour necrosis factor-alpha (TNF alpha) and interleukin-6 (IL-6)] were determined by ELISA assays. mRNA levels in the perirenal fat were determined by real-time PCR.Key findings 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 TNF alpha compared to the STZ-only treated rats (all P< 0.05).Conclusions 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.