Empagliflozin Treatment Attenuates Hepatic Steatosis by Promoting White Adipose Expansion in Obese TallyHo Mice.

Sodium-glucose co-transporters (SGLTs) serve to reabsorb glucose in the kidney. Recently, these transporters, mainly SGLT2, have emerged as new therapeutic targets for patients with diabetes and kidney disease; by inhibiting glucose reabsorption, they promote glycosuria, weight loss, and improve glucose tolerance. They have also been linked to cardiac protection and mitigation of liver injury. However, to date, the mechanism(s) by which SGLT2 inhibition promotes systemic improvements is not fully appreciated. Using an obese TallyHo mouse model which recapitulates the human condition of diabetes and nonalcoholic fatty liver disease (NAFLD), we sought to determine how modulation of renal glucose handling impacts liver structure and function. Apart from an attenuation of hyperglycemia, Empagliflozin was found to decrease circulating triglycerides and lipid accumulation in the liver in male TallyHo mice. This correlated with lowered hepatic cholesterol esters. Using in vivo MRI analysis, we further determined that the reduction in hepatic steatosis in male TallyHo mice was associated with an increase in nuchal white fat indicative of “healthy adipose expansion”. Notably, this whitening of the adipose came at the expense of brown adipose tissue. Collectively, these data indicate that the modulation of renal glucose handling has systemic effects and may be useful as a treatment option for NAFLD and steatohepatitis.

葡萄糖转运蛋白（SGLT）最近在肾脏中吸收葡萄糖。但是，迄今为止，SGLT2抑制的机制使用肥胖的小鼠模型对全身性改进进行了理解，该模型概括了糖尿病的人类状况和非酒精性脂肪肝病（NAFLD），我们试图确定肾脏葡萄糖处理的调制如何影响肝脏结构和功能。 ho鼠使用体内MRI分析降低了肝胆固醇，我们进一步确定了雄性Tally Tallyho小鼠的肝脏脂肪变化与Nucal White脂肪的增加有关NAFLD和脂肪性肝炎。