Circulating endocannabinoids in insulin sensitive vs. Insulin resistant obese postmenopausal women. A MONET group study

Authors

  • Joseph Abdulnour,

    1. School of Human Kinetics Faculty of Health Science, University of Ottawa, Ottawa, ON, Canada
    2. Behavioural and Metabolic Research Unit, University of Ottawa, Ottawa, Ontario, Canada
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  • Siham Yasari,

    1. School of Human Kinetics Faculty of Health Science, University of Ottawa, Ottawa, ON, Canada
    2. Behavioural and Metabolic Research Unit, University of Ottawa, Ottawa, Ontario, Canada
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  • Rémi Rabasa-Lhoret,

    1. PROMD Platfrom for research in Obesity Metabolism and Diabetes, Montreal institute for clinical research (IRCM), Montreal, Quebec, Canada
    2. Nutrition department faculty of medecine, Université de Montréal, Montréal, Quebec, Canada
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  • May. Faraj,

    1. PROMD Platfrom for research in Obesity Metabolism and Diabetes, Montreal institute for clinical research (IRCM), Montreal, Quebec, Canada
    2. Nutrition department faculty of medecine, Université de Montréal, Montréal, Quebec, Canada
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  • Stefania Petrosino,

    1. Endocannabinoid Research Group Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Pozzuoli, NA, Italy
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  • Fabiana Piscitelli,

    1. Endocannabinoid Research Group Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Pozzuoli, NA, Italy
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  • Denis Prud' homme,

    1. School of Human Kinetics Faculty of Health Science, University of Ottawa, Ottawa, ON, Canada
    2. Behavioural and Metabolic Research Unit, University of Ottawa, Ottawa, Ontario, Canada
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  • Vincenzo Di Marzo

    1. Endocannabinoid Research Group Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Pozzuoli, NA, Italy
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  • Funding agencies: This research was supported by the Canadian Institutes of Health Research (T 0602145.02), and an operating grant from genome Quebec (Complications Associated with obesity; CAO). Rémi Rabasa-Lhoret holds a scholarship from FRSQ (Fonds de Recherche en Santé du Québec and is the recipient of the J-A DeSéve chair in clinical research). Siham Yasari is currently employed by the Canadian Institutes of Health Research and she declares no conflict of interests. Vincenzo Di Marzo and Fabiana Piscitelli are recipients of an NIH grant (DA-009789).

  • Disclosure: The authors declare no conflict of interest.

  • Author Contributions: Joseph Abdulnour, Siham Yasari, Remi Rabasa-Lhoret, Vincenzo Di Marzo and Denis Prud'homme played a role in the conception/design as well as the acquisition of data. Stefania Petrosino and Fabiana Piscitelli carried out the endocannabinoid measurements. All authors were involved in writing and interpreting the paper and gave final approval of the submitted and published versions.

Abstract

Objective

To measure the circulating levels of endocannabinoids and related molecules at fasting, after acute hyperinsulinemia and after weight loss in insulin sensitive vs. insulin resistant obese postmenopausal women.

Design and Methods

The sample consisted of 30 obese postmenopausal women (age: 58.9 ± 5.2 yrs; BMI: 32.9 ± 3.6 kg/m2). Subjects underwent a 3-hour hyperinsulinaemic-euglycaemic clamp (HEC) (glucose disposal rate (M-value): 10.7 ± 3.3 mg min−1 kg−1 FFM) and 6-month weight loss intervention. Participants were classified as insulin sensitive obese (ISO) or insulin resistant obese (IRO) based on a predefined cutoff. Plasma levels of the endocannabinoids, anandamide (AEA), 2-arachidonoylglycerol (2-AG), and of the AEA-related compounds, palmitoylethanolamide (PEA) and oleoylethanolamide (OEA), were measured by liquid chromatography-mass spectrometry.

Results

IRO presented higher levels of 2-AG (P < 0.05) independently of the HEC and weight loss, whereas the HEC had an independent inhibitory effect on AEA, PEA, and OEA levels (P < 0.05) in both groups. Furthermore, there was an independent stimulatory effect of weight loss only on PEA levels in both groups (P < 0.05).

Conclusions

This study is the first to show that higher circulating levels of the endocannabinoid 2-AG are found in IRO compared to ISO postmenopausal women, and that weight loss is associated with an increase in PEA, a PPAR-α ligand.

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