Endocrine Abstracts

JOINT2441

Background: Western diet which is characterized by a high content of sugar and saturated fat is well known to be associated with obesity, insulin resistance, type 2 diabetes and cardiovascular disease. While chronic kidney disease has long been thought to be the consequence of metabolic disease, it has only recently become clear, that renal damage at an early stage plays a key role in pathophysiology and course of metabolic disease. Underlining the close correlation, SGLT-2 inhibitors and GLP-1 receptor agonists have been shown to improve both, metabolic disease and chronic kidney disease.

Aim: Here we aimed to test whether Western diet causes renal damage by affecting hemodynamically and metabolically important renal transporters in a murine model of diet-induced obesity. Additionally, we aimed to test whether potential harmful effects are reversible by switching the diet from a Western type to a more beneficial one.

Method: Male C57BL/6 mice were fed ad libitum a Western diet for 10 weeks and afterwards switched to either standard diet for eight more weeks or continued to be fed a Western diet. Mice fed standard diet for 18 weeks served as control group.

Results: Western diet feeding for 18 weeks was associated with excess weight gain and development of insulin resistance. Sodium glucose transporter 1 (SGLT1) mRNA expression was significantly higher in kidneys of mice fed a Western diet for 18 weeks than in standard diet fed mice and those switched from Western diet to standard diet after 10 weeks. Additionally, renal sodium glucose transporter 2 (SGLT2) levels were also found to be elevated in Western diet fed mice, showing an already significant difference after 10 weeks and even higher levels after 18 weeks. Importantly, renal SGLT-2 mRNA expressions were comparable in mice fed a Western diet for 18 weeks and in those switched from Western diet to standard diet. Complementary to the upregulation of SGLT2 a downregulation of renal epithelial sodium channel (ENaC) mRNA was observed, which could not be prevented by the dietary switch neither.

Conclusions: Our data show that Western diet causes partially irreversible alterations in renal glucose and sodium transporters that might play a crucial role in development and course of metabolic disease. Importantly, SGLT-2 overexpression occurs early and is not dependent on overt hyperglycemia.