Identification of Scd5 as a functional regulator of visceral fat deposition and distribution
Qi Zhang,
Shaoyang Sun,
Yinglan Zhang,
Xu Wang,
Qiang Li
Affiliations
Qi Zhang
Translational Medical Center for Development and Disease, Shanghai Key Laboratory of Birth Defect Prevention and Control, Institute of Pediatrics, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai 201102, China
Shaoyang Sun
Cancer Institute, Pancreatic Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Shanghai Pancreatic Cancer Institute, Shanghai Key Laboratory of Radiation Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, China; Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
Yinglan Zhang
Translational Medical Center for Development and Disease, Shanghai Key Laboratory of Birth Defect Prevention and Control, Institute of Pediatrics, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai 201102, China
Xu Wang
Cancer Institute, Pancreatic Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Shanghai Pancreatic Cancer Institute, Shanghai Key Laboratory of Radiation Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, China; Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China; Corresponding author
Qiang Li
Translational Medical Center for Development and Disease, Shanghai Key Laboratory of Birth Defect Prevention and Control, Institute of Pediatrics, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai 201102, China; Corresponding author
Summary: 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.