Adipocyte YTH N(6)-methyladenosine RNA-binding protein 1 protects against obesity by promoting white adipose tissue beiging in male mice

Nat Commun. 2023 Mar 13;14(1):1379. doi: 10.1038/s41467-023-37100-z.

Abstract

Obesity, one of the most serious public health issues, is caused by the imbalance of energy intake and energy expenditure. N(6)-methyladenosine (m6A) RNA modification has been recently identified as a key regulator of obesity, while the detailed mechanism is elusive. Here, we find that YTH RNA binding protein 1 (YTHDF1), an m6A reader, acts as an essential regulator of white adipose tissue metabolism. The expression of YTHDF1 decreases in adipose tissue of male mice fed a high-fat diet. Adipocyte-specific Ythdf1 deficiency exacerbates obesity-induced metabolic defects and inhibits beiging of inguinal white adipose tissue (iWAT) in male mice. By contrast, male mice with WAT-specific YTHDF1 overexpression are resistant to obesity and shows promotion of beiging. Mechanistically, YTHDF1 regulates the translation of diverse m6A-modified mRNAs. In particular, YTHDF1 facilitates the translation of bone morphogenetic protein 8b (Bmp8b) in an m6A-dependent manner to induce the beiging process. Here, we show that YTHDF1 may be an potential therapeutic target for the management of obesity-associated diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes* / metabolism
  • Adipose Tissue, White* / metabolism
  • Animals
  • Diet, High-Fat / adverse effects
  • Energy Metabolism
  • Male
  • Mice
  • Obesity / metabolism
  • RNA-Binding Proteins* / genetics
  • RNA-Binding Proteins* / metabolism

Substances

  • N-methyladenosine
  • RNA-Binding Proteins
  • Ythdf1 protein, mouse