Two isoforms of leptin in the White-clouds Mountain minnow (Tanichthys albonubes): Differential regulation by estrogen despite similar response to fasting

• Two leptins, similar in protein structure but distinct in a.a. sequence, were isolated in T. albonubes.
• T. albonubes leptin-A, the dominated form, is primarily expressed in liver with sexual dimorphism.
• Expression of both T. albonubes leptin-A and -B may both increase after long-term fasting.
• We first demonstrated fish leptin-A and -B under differential regulation of estrogen.
• We supplied evidences for leptin as a crucial link between nutritional status and reproduction in fish.

Leptin has been well-established as a canonical anorexic peptide hormone in mammals, though much of its function in fish remains obscure. In this study, the cDNAs of two leptin isoforms (leptin-A and leptin-B) were cloned from the liver of a small cyprinid fish, Tanichthys albonubes. The two T. albonubes leptins, sharing low primary amino acid sequence homology with their mammalian counterparts, and between themselves, are highly conserved in three-dimensional protein structures and gene structures. Liver is a major source of leptin mRNA in T. albonubes with leptin-A being the dominant form. The expression of hepatic leptin-A but not leptin-B mRNA in female fish is significantly higher than in male fish. Transcriptional hepatic levels of leptin-A and leptin-B in both male and female fish were demonstrated to increase after long-term fasting (10–25 days) but decline upon re-feeding (3 days). Strikingly, estrogen (E2) administration induced only leptin-A but not leptin-B hepatic mRNA expression in both male and female fish. Our study here provides the first evidence for differential regulation of two leptins in fish, and sheds new light on the possible origin of leptin in lower vertebrates.