CRISPRa-based activation of Fgf21 and Fndc5 ameliorates obesity by promoting adipocytes browning.

ABSTRACT:

Background

Skeletal muscle-secreted myokines widely participate in lipids metabolism through autocrine, paracrine and endocrine actions. The myokines represented by FGF21 and Irisin can promote the browning of adipocytes and serve as promising targets for treating obesity. Although recombinant myokines replacement therapy and AAV (adeno-associated virus)-based myokines overexpression have shown a definite effect in ameliorating obesity, novel myokine activation strategies with higher efficacy and safety are still in pressing need. This study aimed to evaluate the therapeutic potential of a novel CRISPR-based myokines activation strategy in obesity treatments.

Methods

In this study, we used lentivirus and a single AAV vector containing dCas9-VP64 with a single-guide RNA to se

SUBMITTER: Zhu H 

PROVIDER: S-EPMC10353577 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature