Identification of Scd5 as a functional regulator of visceral fat deposition and distribution

Ectopic deposition of visceral adipose tissue (VAT) in abdomen is usually accompanied with systematic chaos of energy metabolism, a higher risk of cardiovascular diseases and type II diabetes. Here, we identified a previously unexplored gene Scd5 as a master regulator of fat distribution, which alone plays a significant role in determining the VAT accumulation. Firstly, zebrafish scd5 had the highest homology with human SCD5 compared to other SCDs in mouse and rat. We then observed that scd5-homozygous mutant zebrafish displayed a puffy, short and rounded apple-shaped figure. Whole-mount micro-CT scan showed that excessive VAT deposition and short spine are responsible for the abnormal body ratio. And the supplementation of ω3-polyunsaturated fatty acid (ω3-PUFA) in dietary significantly decreased VAT accumulation in scd5(−/−) zebrafish. Lastly, transcriptional analyses revealed that the Wnt, PPAR, C/EBP, and fat synthesis signaling pathways are significantly affected in the VAT of scd5(−/−) mutant and restored by ω3-PUFA.