Abstract
RationaleLipid metabolism contributes to the formation of obesity-related glomerulopathy (ORG). Heart-type fatty acid binding protein (H-FABP or FABP3) is involved in lipid metabolism and was predicted to relate to renal lesions in obesity.MethodsA total of 28 patients with ORG were investigated, and renal tissue from 7 kidney donors served as controls. Db/db mice with albuminuria were treated with Simvastatin for 12 weeks.ResultsImmunohistochemistry demonstrated the H-FABP staining in glomerular and tubular areas of patients with ORG, and the percentage of H-FABP in the glomerular area was significantly higher than in controls (15.8±1.62 versus 4.51±0.56%, P<0.001). Moreover, H-FABP expression correlated with proteinuria, high-density lipoprotein (HDL) cholesterol, waist circumference and the homeostatic model assessment – insulin resistance (HOMA-IR) among patients with ORG. Enhanced expression of H-FABP was also detected in the db/db mice, and expression increased from 8 to 20 weeks of age and was weakly related to increased albuminuria (r = 0.433; P = 0.020). Furthermore, H-FABP was co-localized with synaptopodin and demonstrated a podocyte pattern distribution. After Simvastation treatment, the urine albumin levels decreased with lipid levels and H-FABP expression in the glomeruli. The expression of H-FABP was related to Simvastatin treatment, albuminuria and triglycerides, while it was only linked with triglycerides and albuminuria (r = 0.643, P = 0.036).ConclusionsThis study confirmed an association of H-FABP with the pathogenesis of clinical and experimental ORG, and suggests that such a process might be related to podocytes and lipid dysmetabolism.
Highlights
Obesity is a major health problem, and its incidence is increasing worldwide [1]
The strong positive areas of H-fatty acid-binding proteins (FABPs) were found in the tubular areas of both healthy controls and obesity-related glomerulopathy (ORG) patients
These observations suggest a possible relationship of H-FABP expression in glomeruli with ORG, and this relationship was further explored with regards to the progression of ORG
Summary
It has been reported to contribute to the development of type 2 diabetes, hypertension, cardiovascular disease and chronic kidney disease (CKD) [2,3]. This type of kidney disease is the so-called ‘obesity-related glomerulopathy (ORG)’ and is characterized by glomerulomegaly with or without focal segmental glomerulosclerosis (FSGS) [4]. Evidence shows that altered lipid metabolism, such as hyperlipidemia and increased free fatty acids (FAs), is an important characteristic of obesity and contributes to renal lesions [6]. We previously demonstrated that lipid dysmetabolism in involved in the development of ORG, and heart-type fatty acid binding protein (H-FABP or FABP3) is especially up-regulated in the glomeruli [8]
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