Abstract:
Stearyl coenzyme A desaturase (SCD), also known as delta-9 desaturase, catalyzes the rate-limiting step in the formation of monounsaturated fatty acids. In mammals, depletion or inhibition of SCD activity generally leads to a decrease in triglycerides and cholesteryl esters. However, the endogenous role of
scd in teleost fish remains unknown. Here, we generated a zebrafish
scd mutant (
scd-/-) to elucidate the role of
scd in lipid metabolism and sexual development. Gas chromatography-mass spectrometry (GC-MS) showed that the
scd -/- mutants had increased levels of saturated fatty acids C16:0 and C18:0, and decreased levels of monounsaturated fatty acids C16:1 and C18:1. The mutant fish displayed a short stature and an enlarged abdomen during development. Unlike
Scd-/- mammals, the
scd-/- zebrafish showed significantly increased fat accumulation in the whole body, especially in the liver, leading to hepatic mitochondrial dysfunction and severe cell apoptosis. Mechanistically,
srebf1, a gene encoding a transcriptional activator related to adipogenesis,
acc1 and
acaca, genes involved in fatty acid synthesis, and
dgat2, a key gene involved in triglyceride synthesis, were significantly upregulated in mutant livers to activate fatty acid biosynthesis and adipogenesis. The
scd-/- males exhibited defective natural mating behavior due to defective genital papillae but possessed functional mature sperm. All defects in the
scd-/- mutants could be rescued by ubiquitous transgenic overexpression of
scd. In conclusion, our study demonstrates that
scd is indispensable for maintaining lipid homeostasis and development of secondary sexual characteristics in zebrafish.