Leptin knockdown reduces metabolic rate in zebrafish

We used antisense morpholino oligonucleotides to knockdown leptin(a) expression in developing zebrafish embryos to ask whether metabolic activity is directly influenced by leptin signaling (as in mammals). Leptin is a pleiotropic protein hormone known to be involved in mammalian energy signaling and storage. Although leptin is well studied in mammals, its function in lower vertebrates is virtually unknown. Leptin expression affects metabolic activity, as assayed by two independent measures of metabolic rate (direct and indirect). Oxygen consumption (PO 2 ) was measured at 28.5°C in batches of ten embryos using a closed system respirometer; leptin morphants had significantly lower metabolic activity at 24 hours post fertilization (P=<0.001). A second, more sensitive assay measured respiration of individual embryos via a pH indicator dye that recorded CO 2 production. Again, the leptin morphants had significantly reduced metabolic rate compared to wild‐type controls at 24 hpf (P=<0.001). Morphants also exhibited morphological changes in the development of the heart suggesting changes in cardiac output, and in yolk absorption. Overall, these data suggest leptin signaling influences metabolic rate in fishes as it does in mammals, and promotes zebrafish as another vertebrate model for studying leptin function. Funded by NIH 1R15DK079282‐01A1 to RLL, QL, and BB.