ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: Cell. 2019;179, 1–17. doi: https://pubmed.ncbi.nlm.nih.gov/31761534/

The current study demonstrates that primary cilia, which are present on all adult mesenchymal stem cells including preadipocytes, play a major role in adipogenic differentiation. Using a transgenic mouse model where all preadipocytes were devoid of cilia, they could elegantly show that cilia are crucial for adipose tissue development. Further, adipogenesis was dependent on a cilia-located G-protein coupled receptor, FFAR4, which senses ω3 fatty acids.

Adipose tissue mass is flexibly controlled in response to nutritional status by altering adipose volume (hypertrophy) and adipocyte number (hyperplasia). As excessive expansion of the adipose tissue by hypertrophy is associated with metabolic complications (1), the adipogenic potential of preadipocyte is a determinant of metabolic health by balancing between hypertrophy and hyperplasia. Understanding the mechanisms which regulate this adipogenic potential might be helpful to develop novel strategies to counteract the metabolic syndrome.

Mechanistically, FFAR4 activation leads to increase of cAMP levels, and downstream activation of the CREB and EPAC signaling pathways. Analysis by transcriptomics and investigating the accessibility of DNA for transcription factors, further revealed the implication of chromatin remodeling in the process of the FFAR4-driven transcriptional adipogenic program. Of note, FFAR4 could not be activated by saturated fatty acids.

Previous studies have demonstrated that dietary supplementation with ω3 fatty acids improves insulin sensitivity and inhibits adipose tissue inflammation in both mice and humans (2). It could be thus speculated that such diets shift adipose expansion towards hyperplasia, by inducing adipogenic potential of preadipocytes. The impact of ω3 fatty acids on adipogenesis in vitro is however controversial, warranting further research.

References:

1. Ghaben AL, Scherer PE. Adipogenesis and metabolic health. Nature Reviews Molecular Cell Biology 2019;20 (4):242–258. doi: 10.1038/s41580-018-0093-z.

2. Spencer M, Finlin BS, Unal R, Zhu B, Morris AJ, Shipp LR, Lee J, Walton RG, Adu A, Erfani R, Campbell M, McGehee Jr RE, Peterson CA, Kern PA. Omega-3 fatty acids reduce adipose tissue macrophages in human subjects with insulin resistance. Diabetes 2013;62 (5):1709–1717. doi: 10.2337/db12-1042.