Abstract

CIntroduction: Early stress alters the endo-cannabinoid system of tissues involved in energy homeostasis, leading to long term consequences associated to hormonal and metabolic disruptions associated to overweight/obesity and insulin resistance. We have previously reported a decreased Anandamide (AEA)-hydrolysing activity in liver and epididymal fat of adult mice previously subjected to stress during lactation, a result that may indicate reduced activity of the enzyme fatty acid amide hydrolase present in both tissues (FAAH; able to hydrolyse the endocannabinoid AEA). Objective: Since at present it is unknown whether early stress affects FAAH gene and/or protein expression in liver and adipose tissue during adulthood, we have performed studies with the aim of evaluating these parameters. Methods: Male mice pups were subjected to a soft nociceptive stress during the first 21 days of life (whole lactation period) with a subcutaneous injection of saline solution in the back, and sacrificed when adults (130 days old) to extract liver and epididymal fat. Results: Data obtained from real time PCR demonstrate that stress during lactation do not affect FAAH mRNA expression either in liver or epididymal adipose tissue of adult animals; however, Western Blot analyses indicates that FAAH protein amount was decreased by 35 and 65% in liver and epididymal fat, respectively. Conclusion: Present results demonstrate that nociceptive stress during lactation leads to decreased FAAH protein expression in liver and epididymal fat of adult mice, which may be associated to the low AEA- hydrolysing activity previously reported by us in both tissues. Low levels and activity of FAAH should result in increased availability of AEA, leading to a sustained activity of type 1 cannabinoid receptors associated to undesirable cellular and physiological consequences

Highlights

  • Adverse health consequences due to inappropriate environmental perinatal conditions may become evident during adulthood as a result of the metabolic plasticity of mammalian organisms [1,2,3]

  • Present results demonstrate that nociceptive stress during lactation leads to decreased Fatty Acid Amide Hydrolyse Activity (FAAH) protein expression in liver and epididymal fat of adult mice, which may be associated to the low a reduced anandamide (AEA)- hydrolysing activity previously reported by us in both tissues

  • Low levels and activity of FAAH should result in increased availability of AEA, leading to a sustained activity of type 1 cannabinoid receptors associated to undesirable cellular and physiological consequences

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Summary

Introduction

Adverse health consequences due to inappropriate environmental perinatal conditions may become evident during adulthood as a result of the metabolic plasticity of mammalian organisms [1,2,3]. NS-mice had a reduced anandamide (AEA)-hydrolysing activity in liver and epididymal fat, a result indicating a low Fatty Acid Amide Hydrolyse Activity (FAAH), the enzyme able to hydrolyse the endocannabinoid AEA. This fact should result in greater amounts and availability of AEA able to induce a sustained activity of CB1R present in those tissues [5,8]. In this regard, it has been recently shown that lack of FAAH activity in FAAH-/- mice promotes energy storage through increased levels of AEA in different tissues, indicating a crucial role for FAAH in energy homeostasis [9]. The importance of FAAH in human obesity has been associated to a mutation responsible for a decreased expression and activity of this enzyme, leading to increased levels of circulating AEA [10,11]

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