Meeting Abstract

55.3  Saturday, Jan. 5  Leptin Function in Zebrafish. LONDRAVILLE, RL*; LIU, Q; DALMAN, MR; BAGATTO, B; Univ. of Akron; Univ. of Akron; Univ. of Akron; Univ. of Akron londraville@uakron.edu

One of the most striking anatomical features of both cold adapted and cold acclimated fishes is their extreme adiposity, with lipid comprising up to 60% of the dry mass of Antarctic fishes. We are investigating the hormone leptin as an approach to understanding both the ‘how’ and ‘why’ of lipid accumulation in fish from cold environments. In mammals, leptin influences appetite, metabolic rate, lipid deposition, lipid metabolism, and many other systems, including bone growth and immune function. Because leptin has not been cloned in polar fishes, we used a genome-enabled model fish (zebrafish, D. rerio) to manipulate leptin expression in developing embryos. Reduced leptin expression (via morpholino oligonucleotides ) results in poor yolk absorption, reduced sensory structures (eyes and ears), reduced otoliths, impaired cardiac function, and significantly reduced metabolic rate. A majority of these effects can be rescued with recombinant zebrafish leptin. Identical or similar effects were seen when we reduced expression of the leptin receptor (also with morpholino oligonucleotides). Leptin’s effects on metabolic rate are similar between mammals and zebrafish, and its effects on sensory structure development may be a clue to hearing loss common in diabetic humans. Reduced leptin signaling was also associated with reduced otolith size. We hypothesize that leptin signaling is disrupted in Antarctic fishes, leading to both lipid accumulation and reduced skeleton mineralization. Supported by NIH 1R15DK079282-01A1 to RLL, QL, and BB.