Adiponectin variants comprising one or more amino acid modifications to corresponding wild-type adiponectins at positions having predetermined hydrophobicity, predetermined polarity, predetermined electrostatic potential, Met, aromatic amino acid, Cys corresponding to position 152 of SEQ ID NO:1, amino acid affecting isoelectric point of the wild-type or variant adiponectin, amino acid affecting beta sheet formation, helix capping, or dipole interactions, or a combination thereof, wherein the adiponectin variants exhibit improved stability, solubility or soluble expression, expression yield, the ability to induce phosphorylation of AMPK, or a combination thereof, as compared to the corresponding wild-type adiponectins.