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Saturated Fatty Acids Stimulate Renal Inflammation‐Related Gene and Protein Expression by Activating the ERK Signaling Pathway
Author(s) -
Zhao Xueying,
Chen Xiaoming,
George Jasmine,
Zhang Yuanyuan,
Cobbs Alyssa,
Wang Guoshen,
Li Lingyun,
Emmett Nerimiah
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.567.9
Subject(s) - endocrinology , medicine , lipotoxicity , diabetic nephropathy , albuminuria , inflammation , kidney , nephropathy , nephrin , biology , diabetes mellitus , insulin resistance , podocyte , proteinuria
Diabetic nephropathy is increasingly recognized as a major contributor to renal dysfunction and kidney failure in obesity and type 2 diabetes. To identify the molecular mediators of kidney injury and dysfunction associated with metabolic syndrome with or without hyperglycemia, we compared renal gene expression profiles in Zucker lean (ZL), Zucker obese (ZO) and Zucker diabetic (ZD) rats. Compared to 20‐week‐old ZL control (glucose: 110 ± 8 mg/dL), both prediabetic ZO (glucose: 157 ± 11 mg/dL) and diabetic ZD (glucose: 481 ± 37 mg/dL) rats displayed hyperlipidemia and kidney injury with high‐degree albuminuria/proteinuria. Using cDNA microarray, we identified 25 inflammatory and fibrotic transcriptomes similarly changed in ZO and ZD kidneys, including kidney injury molecule‐1 (KIM‐1), secreted phosphoprotein‐1 (SPP‐1) and CD44. Immunostaining and Western blot analyses confirmed an increase in their protein levels in the kidney of ZO and ZD rats. Moreover, our in vitro cell culture study revealed that administration of saturated fatty acid palmitate resulted in an upregulation of KIM‐1, SPP‐1 and CD44 protein expression in primary tubular epithelial cells. Palmitate‐induced tubular inflammation and injury‐associated proteins were greatly attenuated in the presence of U0126, an inhibitor of extracellular signal‐regulated kinase 1/2 (ERK1/2). Taken together, our results demonstrate a stimulatory role of lipids for inflammation‐related gene and protein expression in the kidney, suggesting that lipotoxicity may play an important part in renal inflammation and nephropathy progression in metabolic syndrome associated with obesity and type 2 diabetes. Support or Funding Information This work was supported by the NIH SC1DK112151, NIH/NCRR/RCMI 8G12MD007602 and 8U54MD007588. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .