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Abstract
Diabetes is becoming increasingly problematic in the United States with 34.2 million total people diagnosed with either Type 1 or Type 2 in 2018. Diabetic individuals who have elevated cholesterol, triglycerides, and blood glucose levels have an increased risk of complications. One complication that individuals are at risk for is diabetic kidney disease (DKD). Previous studies have shown that elevated triglyceride-rich lipoproteins (TRLs) are elevated in those diagnosed with diabetes and are associated with DKD progression. Further, lipids are thought to contribute to kidney function decline through altering different cells in the kidney glomerulus namely endothelial cells, podocytes, sand mesangial cells. Even with the vast knowledge and previous research on how lipids interact with different cells in the progression to DKD, the exact role of dyslipidemia and hyperglycemia on progression to DKD in diabetic patients is still not well understood.Therefore, in this study, we used mouse models that were diabetic and dyslipidemic to mimic human DKD progression, to investigate the direct effects of TRL accumulation in DKD progression. Immunohistochemistry (IHC) was performed on sacrificed diabetic and dyslipidemic mouse kidneys to assess whether lipids were accumulating and where. After our initial findings indicated around half of the lipid droplets did not overlap with macrophages, we explored other cell types that may be impacted by diabetic conditions. We extracted endothelial cells, which are known to take up lipids and are sensitive to lipotoxic stimuli, from mouse kidneys and stimulated them with diabetic and dyslipidemic conditions. Additionally, kidney cells from diabetic and wildtype mice were extracted to explore whether changes to endothelial cells also occur in vivo. In this study, we observed that macrophages were accumulating and are lipid-loaded in diabetic and dyslipidemic mice. Further, kidney endothelial cells responded primarily to elevated glucose levels resulting in increased expression of Ccl2, a key mediator of monocyte recruitment. These findings are a starting point in understanding how dyslipidemia and diabetic conditions affect different cells in the glomerulus and drive DKD progression and can help development treatments and prevention of DKD progression.
