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Background <p>The endocannabinoid system and its extension, the endocannabinoidome (eCBome), are lipid-based signalling systems involved in regulating energy balance and metabolic homoeostasis. The eCBome includes a variety of bioactive lipids derived from fatty acids, such as <i>N</i>-acylethanolamines (NAEs) and 2-monoacyl-glycerols (2‑MAGs), which have been linked to different patterns of adiposity. Dietary intake, particularly fatty acid intake, plays a key role in shaping the circulating eCBome profile. Bariatric surgery and subsequent diet modifications can significantly modulate the eCBome, potentially restoring metabolic balance in individuals with obesity.</p> Aim <p>The aim of the study is to identify longitudinal changes in the circulating profile of eCBome mediators in individuals living with severe obesity, before and after a sleeve gastrectomy, and to relate these changes to metabolic improvements and changes in dietary intake.</p> Methods <p>The cohort includes 33 adults with severe obesity (BMI ≥ 35&#xa0;kg/m²), awaiting a sleeve gastrectomy. Blood samples, anthropometric measurements, metabolic profile and dietary intakes (assessed via 24&#xa0;h dietary recalls) were collected before and 4 months after surgery. Circulating eCBome mediators were quantified by liquid-chromatography tandem mass spectrometry in fasting plasma samples.</p> Results <p>Four months after sleeve gastrectomy, reductions in adiposity (BMI, body fat mass, waist and neck circumferences) and improvements in metabolic parameters (triglycerides, high-density lipoprotein cholesterol levels and fasting insulin) were accompanied by significant changes in the levels of some circulating eCBome mediators. Post-surgery circulating levels of EPEA and DHEA reduced, whereas levels of 2-AG, 2-LG, 2-DPG and 2-DHG increased after adjusting for pre-surgery levels and sex (<i>P</i> &lt; 0.05). Interestingly, the circulating levels of eCBome mediators within each family (i.e., NAEs and 2-MAGs) were more closely intercorrelated after surgery than before. Adiposity measurements and dietary fatty acid intakes, such as arachidonic acid and omega-3 fatty acids, were associated with the circulating eCBome profile only after surgery.</p> Conclusion <p>Weight loss and metabolic profile improvements induced by sleeve gastrectomy correlate with changes in the circulating eCBome profile. In severe obesity, neither adiposity nor dietary fatty acid intake appear to directly influence the circulating eCBome profile. The contribution of these factors, which had been previously observed in individuals with normal weight to moderate obesity, only becomes evident following weight loss.</p>

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Longitudinal changes in endocannabinoidome and dietary lipid profile in severe obesity: impact of sleeve gastrectomy

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月15日

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  • Gabrielle St-Arnaud,
  • Justine Daoust,
  • Mélissa Pelletier,
  • Caroline Gagnon,
  • Laurent Biertho,
  • Léonie Bouvet-Bouchard,
  • Elizabeth Dumais,
  • Nicolas Flamand,
  • Vincenzo Di Marzo,
  • Andréanne Michaud,
  • Alain Veilleux

摘要

Background

The endocannabinoid system and its extension, the endocannabinoidome (eCBome), are lipid-based signalling systems involved in regulating energy balance and metabolic homoeostasis. The eCBome includes a variety of bioactive lipids derived from fatty acids, such as N-acylethanolamines (NAEs) and 2-monoacyl-glycerols (2‑MAGs), which have been linked to different patterns of adiposity. Dietary intake, particularly fatty acid intake, plays a key role in shaping the circulating eCBome profile. Bariatric surgery and subsequent diet modifications can significantly modulate the eCBome, potentially restoring metabolic balance in individuals with obesity.

Aim

The aim of the study is to identify longitudinal changes in the circulating profile of eCBome mediators in individuals living with severe obesity, before and after a sleeve gastrectomy, and to relate these changes to metabolic improvements and changes in dietary intake.

Methods

The cohort includes 33 adults with severe obesity (BMI ≥ 35 kg/m²), awaiting a sleeve gastrectomy. Blood samples, anthropometric measurements, metabolic profile and dietary intakes (assessed via 24 h dietary recalls) were collected before and 4 months after surgery. Circulating eCBome mediators were quantified by liquid-chromatography tandem mass spectrometry in fasting plasma samples.

Results

Four months after sleeve gastrectomy, reductions in adiposity (BMI, body fat mass, waist and neck circumferences) and improvements in metabolic parameters (triglycerides, high-density lipoprotein cholesterol levels and fasting insulin) were accompanied by significant changes in the levels of some circulating eCBome mediators. Post-surgery circulating levels of EPEA and DHEA reduced, whereas levels of 2-AG, 2-LG, 2-DPG and 2-DHG increased after adjusting for pre-surgery levels and sex (P < 0.05). Interestingly, the circulating levels of eCBome mediators within each family (i.e., NAEs and 2-MAGs) were more closely intercorrelated after surgery than before. Adiposity measurements and dietary fatty acid intakes, such as arachidonic acid and omega-3 fatty acids, were associated with the circulating eCBome profile only after surgery.

Conclusion

Weight loss and metabolic profile improvements induced by sleeve gastrectomy correlate with changes in the circulating eCBome profile. In severe obesity, neither adiposity nor dietary fatty acid intake appear to directly influence the circulating eCBome profile. The contribution of these factors, which had been previously observed in individuals with normal weight to moderate obesity, only becomes evident following weight loss.