scd knockout activates β-oxidation of fatty acids via accumulating stearic acid (18:0) and induces anorexia in zebrafish

Gene. 2023 Jun 30:871:147431. doi: 10.1016/j.gene.2023.147431. Epub 2023 Apr 15.

Abstract

Stearoyl-CoA desaturase (scd) is the rate-limiting enzyme for the biosynthesis of monounsaturated fatty acids (MUFA), and it plays a critical role in regulating hepatic lipogenesis and lipid oxidation. However, its role in teleosts remains unclear. In this study, we generated scd knockout zebrafish (scd-/-) to explore the role of Scd in regulating growth and metabolism in teleosts. The results showed that scd knockout reduces hepatic lipid deposition by down-regulating the expression of lipogenesis-related genes and up-regulating the expression of lipolysis-related genes. In addition, the knockout of scd suppressed food intake and reduced body weight. Further analysis confirmed that scd knockout suppressed the feeding behavior by decreasing expression of orexigenic peptide genes and increasing expression of anorexigenic peptide genes. The high-level stearic acid (18:0) feeding experiment results showed that the accumulation of 18:0 inhibited feeding behavior, reduced food intake, decreased body weight, and increased lipid β-oxidation, which was essentially consistent with the phenotypes of scd deficiency. Taken together, our results indicate that the knockout of scd inhibited the food intake through the accumulation of 18:0. This study preliminarily reveals the role of Scd in regulating food intake of teleosts, which provides theoretical basis for the functional study of Scd.

Keywords: Behavioral analysis; Food intake; Lipid deposition; Scd; Stearic acid.

MeSH terms

  • Animals
  • Anorexia
  • Body Weight
  • Fatty Acids*
  • Fatty Acids, Monounsaturated
  • Stearic Acids
  • Stearoyl-CoA Desaturase* / genetics
  • Stearoyl-CoA Desaturase* / metabolism
  • Zebrafish / genetics
  • Zebrafish / metabolism

Substances

  • Fatty Acids
  • Stearoyl-CoA Desaturase
  • Stearic Acids
  • Fatty Acids, Monounsaturated