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  • Accepted Manuscript: Transcriptomic coordination at hepatic steatosis indicates robust immune cell engagement prior to inflammation
Title: Transcriptomic coordination at hepatic steatosis indicates robust immune cell engagement prior to inflammation
Abstract Background Deregulation in lipid metabolism leads to the onset of hepatic steatosis while at subsequent stages of disease development, the induction of inflammation, marks the transition of steatosis to non-alcoholic steatohepatitis. While differential gene expression unveils individual genes that are deregulated at different stages of disease development, how the whole transcriptome is deregulated in steatosis remains unclear. Methods Using outbred deer mice fed with high fat as a model, we assessed the correlation of each transcript with every other transcript in the transcriptome. The onset of steatosis in the liver was also evaluated histologically. Results Our results indicate that transcriptional reprogramming directing immune cell engagement proceeds robustly, even in the absence of histologically detectable steatosis, following administration of high fat diet. In the liver transcriptomes of animals with steatosis, a preference for the engagement of regulators of T cell activation and myeloid leukocyte differentiation was also recorded as opposed to the steatosis-free livers at which non-specific lymphocytic activation was seen. As compared to controls, in the animals with steatosis, transcriptome was subjected to more widespread reorganization while in the animals without steatosis, reorganization was less extensive. Comparison of the steatosis and non-steatosis livers showed high retention of coordination suggesting more » that diet supersedes pathology in shaping the transcriptome’s profile. Conclusions This highly versatile strategy suggests that the molecular changes inducing inflammation proceed robustly even before any evidence of steatohepatitis is recorded, either histologically or by differential expression analysis. « less
Authors:
; ;
Award ID(s):
1736150
Publication Date:
NSF-PAR ID:
10250244
Journal Name:
BMC Genomics
Volume:
22
Issue:
1
ISSN:
1471-2164
Sponsoring Org:
National Science Foundation
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