FABP1: A Potential Biomarker for Nephropathy in Type II Diabetes

Abstract

Aims of the studyNephropathy is an important and frequent complication of diabetes mellitus. Diabetic nephropathy (DN) is also the leading cause of end stage renal disease in most parts of the world. Albuminuria is the hallmark of DN although recent observations suggest that non‐albuminuric nephropathy accounts for as much as 40% of all cases of DN. There is a need for additional and more accurate biomarkers for diagnosis and prognosis of DN. Fatty acid binding protein 1 (FABP1) is normally expressed in the liver but also in the kidney in human and animal DN models. However, it has not been detected in normal rat kidneys. We hypothesized that FABP1 is consistently elevated in the kidneys of experimental nephropathy of type II diabetes and could be a diagnostic biomarker and may have a potential pathogenic role.MethodsMale and female ZSF1 rats were used as an experimental model for nephropathy in type II diabetes and CD rats (non‐diabetic rats) were used as controls. Animals were studied from 8th week and sacrificed at 40 weeks. Kidneys were harvested and tissue homogenates were used for total RNA extraction for Next Gen sequencing and protein extraction for western blots. Serum and urine samples were also collected at the start and end of the study to quantitate the renal function and excretion of markers.ResultsThe ZSF1 rats spontaneously developed obesity, diabetes and hyperlipidemia as expected. Male rats developed more severe hyperglycemia, renal failure and proteinuria (data previously communicated) than females. Next Gen Sequencing of kidney tissue revealed amongst other findings a 1396‐fold increased expression of FABP1. Examination of kidney tissue protein homogenates for the expression of FABP1 showed increased expression especially in the male ZSF1 rats. Examination of urine samples for the presence of FABP1 by ELISA showed remarkably increased levels (12 to15‐fold in males and 6 to 7‐fold in females) increase compared to CD rats. (See figure 1)ConclusionsBoth male and female ZSF1 rats developed metabolic syndrome and nephropathy although the disease was much more severe in male rats. FABP1 was expressed more in male rat kidneys compared to female and control rat kidneys. Additionally, the urine excretion of FABP1 was increased in both male and female ZSF1 rats compared to control rats. These data suggest FABP1 may be a potential biomarker in DN. Additional studies are warranted to examine the mechanisms driving the robust renal FABP1 production/excretion and the possible pathogenic role and potential of FABP1 as a therapeutic target in DN.