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

Diabetology & Metabolic Syndrome

Miguel N Llanos¹  Valeska A Castillo¹  Carolina A Aguirre¹ 

[1] Laboratorio de Nutrición y Regulación Metabólica, Instituto de Nutrición y Tecnología de los Alimentos (INTA), Universidad de Chile, Casilla 138-11, El Líbano, 5524 Santiago, Chile

关键词: Adipose tissue;    Endocannabinoid system;    Insulin resistance;    Overweight;    Anandamide;   

Others  :  814909
DOI  :  10.1186/1758-5996-4-35

 received in 2012-02-13, accepted in 2012-07-23,  发布年份 2012

【 摘 要 】

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.

【 授权许可】

   
2012 Aguirre et al.; licensee BioMed Central Ltd.

【 图 表 】

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