Unknown

Dataset Information

0

Feedback repression of PPARα signaling by Let-7 microRNA.


ABSTRACT: Peroxisome proliferator-activated receptor α (PPARα) controls hepatic lipid homeostasis and is the target of lipid-lowering fibrate drugs. PPARα activation represses expression of let-7 microRNA (miRNA), but the function of let-7 in PPARα signaling and lipid metabolism is unknown. In the current study, a hepatocyte-specific let-7b/c2 knockout (let7b/c2ΔHep) mouse line is generated, and these mice are found to exhibit pronounced resistance to diet-induced obesity and fatty liver. Let-7 inhibition by hepatocyte-specific let-7 sponge expression shows similar phenotypes as let7b/c2ΔHep mice. RNA sequencing (RNA-seq) analysis reveals that hepatic PPARα signaling is repressed in let7b/c2ΔHep mice. Protein expression of the obligate PPARα heterodimer partner retinoid X receptor α (RXRα) is reduced in the livers of let7b/c2ΔHep mice. Ring finger protein 8 (Rnf8), which is a direct target of let-7, is elevated in let7b/c2ΔHep mouse liver and identified as a E3 ubiquitin ligase for RXRα. This study highlights a let-7-RNF8-RXRα regulatory axis that modulates hepatic lipid catabolism.

SUBMITTER: Yagai T 

PROVIDER: S-EPMC8424520 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC6418111 | biostudies-literature
| S-EPMC4539989 | biostudies-literature
| S-EPMC7334544 | biostudies-literature
| S-EPMC4164778 | biostudies-literature
| S-EPMC4359369 | biostudies-literature
| S-EPMC4627294 | biostudies-literature
| S-EPMC1994933 | biostudies-literature
| S-EPMC2906317 | biostudies-literature
| S-EPMC3268329 | biostudies-literature
| S-EPMC5769744 | biostudies-literature