Heart-Type Fatty Acid Binding Protein Is Associated with Proteinuria in Obesity

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%, Pr = 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.研究背景 脂代谢（lipid metabolism）参与肥胖相关肾小球病（obesity-related glomerulopathy, ORG）的发生。心脏型脂肪酸结合蛋白（heart-type fatty acid binding protein, H-FABP 或 FABP3）参与脂代谢过程，此前被预测与肥胖相关的肾脏损伤存在关联。方法 本研究共纳入28例肥胖相关肾小球病患者，并以7名肾脏捐献者的肾组织作为对照。对出现白蛋白尿的db/db小鼠给予辛伐他汀（Simvastatin）干预12周。结果 免疫组化检测显示，肥胖相关肾小球病患者的肾小球及肾小管区域可见H-FABP染色，且肾小球区域的H-FABP阳性占比显著高于对照组（15.8±1.62 vs 4.51±0.56%，Pr=0.433；P=0.020）。进一步研究发现，H-FABP与突触足蛋白（synaptopodin）共定位，并呈现足细胞样分布模式。经辛伐他汀治疗后，小鼠尿白蛋白水平随血脂及肾小球内H-FABP表达水平一同下降。H-FABP的表达水平与辛伐他汀干预、白蛋白尿及甘油三酯水平相关，其中仅与甘油三酯和白蛋白尿呈显著相关性（r=0.643，P=0.036）。结论 本研究证实H-FABP与临床及实验性肥胖相关肾小球病的发病机制存在关联，提示该病理过程可能与足细胞及脂质代谢紊乱相关。