Excess of the endocannabinoid anandamide during lactation induces overweight, fat accumulation and insulin resistance in adult mice

To evaluate long-term effects of AEA treatment during lactation on body weight, epididymal fat accumulation and related metabolic parameters during adulthood.Male mice pups were orally treated with a solution of AEA (20？μg/g body weight in soy oil) or vehicle during the whole lactation period. After weaning, food intake and body weight were recorded every 10？days. Adult animals were subjected to glucose and insulin tolerance tests. Subsequently, animals were sacrificed and epididymal fat pads were extracted. Circulating levels of plasma insulin, leptin, non-sterified fatty acids (NEFA), triglyceride and cholesterol were also evaluated.AEA-treated mice during lactation showed a significant increase in accumulated food intake, body weight and epididymal fat during adulthood when compared to control mice. When evaluating CB1R protein expression in epididymal fat, the AEA-treated group showed a 150？% increase in expression compared to the control mice. This group also displayed significantly higher levels of circulating glucose, insulin, leptin, triglycerides, cholesterol and NEFA. Moreover, a marked state of insulin resistance was an important finding in the AEA-treated group.This study showed that overweight, accumulation of visceral fat and associated metabolic disturbances, such as a higher lipid profile and insulin resistance, can be programmed by a treatment with the endocannabinoid AEA during lactation in adult mice.The increased body of research referring to early life events with long-term consequences, arose from earlier epidemiological studies linking environmental conditions during infancy to a higher risk of disease and mortality in adulthood [1,2]. This situation is a consequence of permanent changes in physiology and/or structure in response to environmental conditions, due to the developmental plasticity of living organisms.Overweight/obesity is a physiopathological condition characterized by an imbalance between energy intake and energy expenditure, whi