Crotamine, originally isolated from
rattlesnake venom, has been extensively studied due to its pleiotropic biological properties, and special attention has been paid to its antitumor activity. However, long-term treatment with
crotamine was accompanied by a reduction in animal
body weight gain and by increases in
glucose tolerance. As
cancer is commonly associated with
cachexia, to preclude the possible
cancer cachexia-like effect of
crotamine, herein this
polypeptide was administered in healthy wild-type C57/BL6 mice by the oral route daily, for 21 days. Reduced
body weight gain, in addition to decreased white adipose tissue (WAT) and increased brown adipose tissue (BAT) mass were observed in healthy animals in the absence of
tumor. In addition, we observed improved
glucose tolerance and increased
insulin sensitivity, accompanied by a reduction of plasma
lipid levels and decreased levels of
biomarkers of liver damage and kidney disfunctions. Importantly, long-term treatment with
crotamine increased the basal metabolic rate in vivo, which was consistent with the increased expression of thermogenic markers in BAT and WAT. Interestingly, cultured brown adipocyte cells induced to differentiation in the presence of
crotamine also showed increases in some of these markers and in lipid droplets number and size, indicating increased brown adipocyte maturation.