The CB₁ receptor antagonist SR141716A reverses adult male mice overweight and metabolic alterations induced by early stress.
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.
Valenzuela
Carina A
CA
Laboratorio de Nutrición y Regulación Metabólica, Instituto de Nutrición y Tecnología de los Alimentos (INTA), Universidad de Chile, Santiago, Chile.
Castillo
Valeska A
VA
Aguirre
Carolina A
CA
Ronco
Ana M
AM
Llanos
Miguel N
MN
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D004822:Epididymis; D005260:Female; D006728:Hormones / Q000097:blood; D008297:Male; D008659:Metabolic Diseases / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D051379:Mice; D050177:Overweight / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology* / Q000627:therapeutic use*; D011247:Pregnancy; D011720:Pyrazoles / Q000494:pharmacology* / Q000627:therapeutic use*; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors; D000077285:Rimonabant; D013315:Stress, Psychological / Q000150:complications* / Q000378:metabolism; D013997:Time Factors
D006728:Hormones; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D000077285:Rimonabant