Hypoxia is the most widespread deleterious consequence of eutrophication and has become a major cause of fishery decline. One feature of chronic exposure to hypoxia in fish is inhibition of feeding. In this study, we investigated if the gene that encodes the appetite-suppressing hormone leptin is regulated by hypoxia in zebrafish (Danio rerio). Exposure of adult zebrafish to hypoxic conditions (1 ± 0.2 mg O₂ L⁻¹) for 4 and 10 days significantly increased leptin-a (zlep-a) mRNA levels in the liver. To evaluate the role of hypoxia-inducible factor 1 (HIF-1) in regulating zlep-a expression, zebrafish embryos were exposed to cobalt chloride (CoCl₂, a HIF-1 inducer) and overexpressed with HIF-1α mRNA. Both CoCl₂ treatment and HIF-1α overexpression markedly increased zlep-a expression in developing embryos, indicating the possible involvement of HIF-1 in zlep-a regulation. In vivo promoter analysis indicated that zlep-a promoter activity is found in the muscle fibers of zebrafish embryos and enhanced by CoCl₂. This is the first report to show that leptin gene expression in fish is regulated by hypoxia possibly via the involvement of HIF-1.
Molecular and Cellular Endocrinology Vol. 319, Issue 1-2, p. 143-146