Fetal Syndrome of Endocannabinoid Deficiency (FSECD) In Maternal Obesity
Introduction
Cannabinoids have been used for the treatment of chronic pain for millenniums [1] with documented results of numerous clinical trials in non-pregnant patients [2]. Exogenous cannabinoids act through the mechanism of “kick-starting” the components of the endogenous cannabinoid system (endocannabinoid [eCB] system, ECS) [3]. ECS is a pharmacological target for the treatment of obesity [4], inflammation [5], cardiovascular and neuronal damage [6], and pain [7], [8]. Clinical syndrome of endocannabinoid deficiency (CECD) is linked to numerous pain-related conditions in adults [9], [10]. First described by Russo in 2004 [10], the concept of CECD has been developed and applied to such conditions as irritable bowel syndrome, fibromyalgia, migraine, and autism [9]. The clinical definition of the syndrome is important, since it leads to the therapeutic application of the cannabis derivatives to its treatment.
The theory of “developmental programming” opens the venue for understanding the origin of adult diseases and their prevention at the most adaptable stage of individual’s life – in the womb. In particular, maternal obesity (MO), affecting 64% of all pregnant women with linear trend toward increase between 2005 and 2014 [11], [12], is associated with significant health risks for mothers and their offspring [13], [14], [15], [16]. However, the results of numerous maternal lifestyle changing trials (i.e. UPBEAT, LIMIT) [17], [18] and surgical interventions for weight reduction remain controversial and unable to demonstrate the benefits of such for fetal and maternal health [18]. Therefore, there is a clear need to identify novel mechanisms and pharmacological targets underlying maternal-fetal interactions under MO conditions.
Remarkably, there is experimental and epidemiological evidence that the spectrum of the diseases which are included in the definition of CECD are “programmed in utero” by MO; however there are no reports available, linking MO and CECD.
Section snippets
Hypothesis
We hypothesize that MO programs offspring health through the mechanism of the Fetal Syndrome of Endocannabinoid Deficiency (FSECD).
This hypothesis differs from the present explanation of the phenomenon of fetal programming by maternal obesity and brings all present theories under the umbrella of one syndrome.
FSECD hypothesis is evident from the perspective of 1) the involvement of ECS in obesity, 2) experimentally-proven shared phenotypes of CECD and diseases, programmed by MO, and 3) evidence
Involvement of endocannabinoid system in obesity
ECS is comprised of long-chain poly-unsaturated fatty acid (n-3 and n-6 LCPUFA) compounds and includes two major ligands: anandamide (AEA) and 2-arachidonoylglycerol (2-AG) [19], which bind to the G-protein coupled receptor family CBR (CBR1 and CBR2) [20]. Overstimulation of endocannabinoid signaling likely plays a causal role in obesity in the non-pregnant state [21], [22]. The dysregulation of ECS has been documented in both models of obesity: 1) overeating [23] and 2) a high fat diet [24].
Acknowledgements
This study was possible thanks to start-up funds from University of Tennessee Health Science Center (Dr. N. S-L and Dr. J.S) and Texas Tech University Health Sciences Center support (Dr. N. S-L and Dr. N. G). Authors are thankful to Dr. Sonali Gupta and the personnel of Labor and Delivery for their help with specimens’ collection.
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