Multi-omic network analysis identified betacellulin as a novel target of omega- 3 fatty acid attenuation of western diet-induced nonalcoholic steatohepatitis

ABSTRACT: Clinical and preclinical studies have established that supplementing diets with ω3 polyunsaturated fatty acids (PUFA) can reduce hepatic dysfunction in nonalcoholic steatohepatitis (NASH). Herein, we used multi-omic network analysis to unveil novel mechanistic targets of ω3 PUFA effects in a preclinical mouse model of western diet induced NASH. After identifying critical molecular processes responsible for the effects of ω3 PUFA, we next performed meta-analysis of human liver cancer transcriptomes and uncovered betacellulin as a key EGFR-binding protein that was induced in liver cancer and downregulated by ω3 PUFAs in animals with NASH. We then confirmed that betacellulin acts by promoting proliferation of quiescent hepatic stellate cells, stimulating transforming growth factor-β2 and incr

SUBMITTER: Dr. Jyothi Padiadpu 

PROVIDER: S-SCDT-10_15252-EMMM_202318367 | biostudies-other |

REPOSITORIES: biostudies-other