Follistatin like-1 (Fstl1) regulates adipose tissue development in zebrafish

Adipocyte. 2024 Dec;13(1):2435862. doi: 10.1080/21623945.2024.2435862. Epub 2024 Dec 7.

Abstract

Obesity is a highly prevalent disorder with complex aetiology. Therefore, studying its associated cellular and molecular pathways may be aided by analysing genetic tractable diseases. In this context, the study of ciliopathies such as Bardet-Biedl syndrome has highlighted the relevance of primary cilia in obesity, both in the central nervous system and peripheral tissues. Based on our previous in vitro results supporting the role of a novel Bbs4-cilia-Fstl1 axis in adipocyte differentiation, we evaluated the in vivo relevance of the zebrafish orthologous genes fstl1a and fstl1b in primary cilia and adipose tissue development. Using a combination of knockdowns and a new fstl1a mutant line, we show that fstl1a promotes primary cilia formation in early embryos and participates in adipose tissue formation in larvae. We also show that fstl1b partially compensates for the loss of fstl1a. Moreover, in high fat diet, fstl1a depletion affects the expression of differentiation and mature adipocyte markers. These results agree with our previous in vitro data and provide further support for the role of FSTL1 as a regulator of adipose tissue formation. Dissecting the exact biological role of proteins such as FSTL1 will likely contribute to understand obesity onset and presentation.

Keywords: Adipose tissue; Bardet–Biedl syndrome; cilia; follistatin-like 1; zebrafish.

MeSH terms

  • Adipocytes / cytology
  • Adipocytes / metabolism
  • Adipogenesis / genetics
  • Adipose Tissue* / metabolism
  • Animals
  • Cell Differentiation
  • Cilia / metabolism
  • Follistatin-Related Proteins* / genetics
  • Follistatin-Related Proteins* / metabolism
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism
  • Zebrafish*

Substances

  • Follistatin-Related Proteins
  • Zebrafish Proteins

Grants and funding

This study was supported by Programa para el Desarrollo de las Ciencias Básicas (PEDECIBA) and Sistema Nacional de Investigadores- Agencia Nacional de Investigación e Innovación (ANII) to LG, IS, MC-R, HN, VP-E, PL and JLB; FCE_1_2019_1_156365 ANII to PL and JLB; Comisión Académica de Posgrados (CAP-UdelaR) to IS; FOCEM – Fondo para la Convergencia Estructural del Mercosur (COF 03/11). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.