Obesity-Dependent Adipokine Chemerin Suppresses Fatty Acid Oxidation to Confer Ferroptosis Resistance.

ABSTRACT: Clear cell renal cell carcinoma (ccRCC) is characterized by accumulation of neutral lipids and adipogenic transdifferentiation. We assessed adipokine expression in ccRCC and found that tumor tissues and patient plasma exhibit obesity-dependent elevations of the adipokine chemerin. Attenuation of chemerin by several approaches led to significant reduction in lipid deposition and impairment of tumor cell growth in vitro and in vivo. A multi-omics approach revealed that chemerin suppresses fatty acid oxidation, preventing ferroptosis, and maintains fatty acid levels that activate hypoxia-inducible factor 2α expression. The lipid coenzyme Q and mitochondrial complex IV, whose biogeneses are lipid-dependent, were found to be decreased after chemerin inhibition, contributing to lip

SUBMITTER: Tan SK 

PROVIDER: S-EPMC8338847 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature