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Leptin is a cytokine-like peptide, predominantly biosynthesized in adipose tissue, which plays an important role in regulating food intake, energy balance and reproduction in mammals. However, how it may have been modified to enable life in the chronic cold is unclear. Here, we identified a  leptin-a  gene ( lepa ) in the cold-adapted and neutrally buoyant Antarctic toothfish  Dissostichus mawsoni  that encodes a polypeptide carrying four α-helices and two cysteine residues forming in-chain disulfide bonds, structures shared by most vertebrate leptins. Quantitative RT-PCR confirmed that mRNA levels of the  leptin-a  gene of  D. mawsoni  (DM- lepa ) were highest in muscle, followed by kidney and liver; detection levels were low in the gill, brain, intestine, and ovary tissues. Compared with  leptin-a  genes of fishes living in warmer waters, DM- lepa  underwent rapid evolution and was subjected to positive selection. Over-expression of DM- lepa  in the zebrafish cell line ZFL resulted in signal accumulation in the cytoplasm and significantly increased cell proliferation both at the normal culture temperature and under cold treatment. DM- lepa  over-expression also reduced apoptosis under low-temperature stress and activated the STAT3 signaling pathway, in turn upregulating the anti-apoptotic proteins bcl2l1, bcl2a, myca and mdm2 while downregulating the pro-apoptotic baxa, p53 and caspase-3. These results demonstrate that DM- lepa , through STAT3 signaling, plays a protective role in cold stress by preventing apoptotic damage. Our study reveals a new role of  lepa  in polar fish.

Leptin Gene Protects Against Cold Stress in Antarctic Toothfish