Oxidant-Induced Alterations in the Adipocyte Transcriptome: Role of the Na,K-ATPase Oxidant Amplification Loop
Year: 2020
Type: article
Abstract: (1) Background: Recently we have noted that adipocyte specific expression of the peptide, NaKtide, which was developed to attenuate the Na,K-ATPase oxidant amplification loop, could ameliorate the phenotypical features of uremic cardiomyopathy. We performed this study to better characterize the cellular transcriptomes that are involved in various biological pathways associated with adipocyte function occurring with renal failure. (2) Methods: RNAseq was performed on the visceral adipose tissue of animals subjected to partial nephrectomy. Specific expression of NaKtide in adipocytes was achieved using an adiponectin promoter. To better understand the cause of gene expression changes in vivo, 3T3L1 adipocytes were exposed to indoxyl sulfate (IS) or oxidized low density lipoprotein (oxLDL), with and without pNaKtide (the cell permeant form of NaKtide). RNAseq was also performed on these samples. (3) Results: We noted a large number of adipocyte genes were altered in experimental renal failure. Adipocyte specific NaKtide expression reversed most of these abnormalities. High correlation with some cardiac specific phenotypical features was noted amongst groups of these genes. In the murine adipocytes, both IS and oxLDL induced similar pathway changes as were noted in vivo, and pNaKtide appeared to reverse these changes. Network analysis demonstrated tremendous similarities between the network revealed by gene expression analysis with IS compared with oxLDL, and the combined in vitro dataset was noted to also have considerable similarity to that seen in vivo with experimental renal failure. (4) Conclusions: This study suggests that the myriad of phenotypical features seen with experimental renal failure may be fundamentally linked to oxidant stress within adipocytes.
DOI: 10.3390/ijms21165923
Authors: Komal Sodhi, James Denvir, Jiang Liu, Juan Sanabria, Yiliang Chen, Roy Silverstein, Zijian Xie, Nader Abraham, Joseph Shapiro
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,112
Awards: G1739031488, Na/K-ATPase Reduction in Renal Disease-Related Cardiac Dysfunction, HORMONAL REGULATION OF BLOOD PRESSURE, Receptor Na/K-ATPase Antagonists As Novel Therapeutics For Renal/Cardiac Diseases, G2987985673, G3161094990, The Role of Oxidative Signaling through Na/K-ATPase in Salt-Sensitive Hypertension, CORAL: Clinical Coordinating Center, G3990278997, Role of Adipocyte Na/K-ATPase Signaling in the Development and Progression of Uremic Cardiomyopathy By Altering Adipocyte Phenotype, G9000063911, G9000067700, G9000164183, G9000187486, G9000271713, West Virginia IDeA Network of Biomedical Research Excellence (WV-INBRE)
OpenAlex ID: W3056976966