RESUMO
BACKGROUND: Environmental conditions in early life can induce permanent physiological changes, sometimes increasing the risk of chronic diseases during adulthood. Neural and peripheral circuits controlling energy balance may be modulated during such a critical period. Since type 1 cannabinoid receptors (CB1R) have recently emerged as targets for modulating energy balance, their premature chronic activation during early life may result in long-term metabolic consequences associated to overweight/obesity. Endogenous activation of CB1R mainly occurs after binding to the endocannabinoid Anandamide (AEA). OBJECTIVE: To evaluate long-term effects of AEA treatment during lactation on body weight, epididymal fat accumulation and related metabolic parameters during adulthood. DESIGN: 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. RESULTS: 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. CONCLUSION: 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.
RESUMO
Perinatal stress may cause metabolic and hormonal disruptions during adulthood. The aim of this study was to evaluate the effects of early postnatal nociceptive stimulation (NS) on body weight and other metabolic parameters during adulthood and to determine whether CB1 endocannabinoid receptors (CB1Rs) may be involved in these effects. Male mice were subjected to NS during lactation with a daily subcutaneous injection of saline solution. Subsequently, both control and NS-mice were treated from day 40 to 130, with an oral dose (1 µg/g body weight) of SR141716A, a specific CB1R antagonist/inverse agonist. Mice body weight and food intake was periodically evaluated. Adult animals were then killed to evaluate epididymal fat pads and metabolic parameters. NS did not influence food intake in adult animals, but caused significant increases in body weight, epididymal fat pads, and circulating levels of leptin, corticosterone, and triglycerides (TGs). Chronic treatment with SR141716A normalized these parameters, with the exception of corticosterone levels. This treatment also reduced plasma levels of glucose, insulin, and total cholesterol in both adult control and NS-mice. In addition, fatty acid (FA) amide hydrolase (FAAH) activity (the enzyme able to hydrolyze endocannabinoids) from liver and epididymal fat of adult NS-mice was decreased by 40-50% in comparison to activities found in same tissues of control mice. Results suggest that overactive liver and epididymal fat CB1R due to early NS may be involved in late metabolic alterations, which are sensitive to chronic treatment with SR141716A.