The Effect of Peripheral Injection of Leptin on Biomarkers of Aging in Calorie Restricted Rats

Background and Objectives: Calorie restriction (CR) is one of the proven methods of extending lifespan and slowing aging. Leptin is a nutritionally regulated adipokine that has been proposed as a possible key signal in the adaptive responses relevant to CR. Under CR, plasma leptin levels decrease, thus it was hypothesized that leptin administration may counteract CR-induced weight loss. Therefore, the effect of leptin administration on modulating CR-induced alterations in some biomarkers of aging was investigated in a rat model. Materials and Methods: Fifty male Wistar rats were fed either ad libitum (AL) or 40% calorie restricted diet for 11 weeks. Then each group randomly assigned to receive 0.5 mg/kg/day intravenous leptin or saline, for 3 days. Fasting blood glucose, insulin, and leptin levels as well as body temperature were measured at the end of the treatment. Results: After CR, all variables including body weight, BMI, body temperature, serum levels of glucose, insulin and leptin decreased significantly compared to the AL group. After 3 days of leptin treatment, no statistically significant differences were observed in body weight, BMI, serum glucose and insulin levels compared to the saline treatment. Body temperature did not change after leptin administration in CR subgroups, but it was significantly higher in AL-leptin compared to AL-saline group. Conclusions: Based on these findings, administration of recombinant leptin was not effective in modulating the alterations of aging biomarkers induced by calorie restriction.