Abstract
Capsaicinoids, the pungent principles of chili peppers and prototypical activators of the transient receptor potential of the vanilloid type-1 (TRPV1) channel, which is a member of the expanded endocannabinoid system known as the endocannabinoidome (eCBome), counteract food intake and obesity. In this exploratory study, we examined the blood and stools from a subset of the participants in a cohort of reproductive-aged women with overweight/obesity who underwent a 12-week caloric restriction of 500 kcal/day with the administration of capsaicinoids (two capsules containing 100 mg of a capsicum annuum extract (CAE) each for a daily dose of 4 mg of capsaicinoids) or a placebo. Samples were collected immediately before and after the intervention, and plasma eCBome mediator levels (from 23 participants in total, 13 placebo and 10 CAE) and fecal microbiota taxa (from 15 participants in total, 9 placebo and 6 CAE) were profiled using LC–MS/MS and 16S metagenomic sequencing, respectively. CAE prevented the reduced caloric-intake-induced decrease in beneficial eCBome mediators, i.e., the TRPV1, GPR119 and/or PPARα agonists, N-oleoyl-ethanolamine, N-linoleoyl-ethanolamine and 2-oleoyl-glycerol, as well as the anti-inflammatory N-acyl-ethanolamines N-docosapentaenyl-ethanolamine and N-docosahexaenoyl-ethanolamine. CAE produced few but important alterations in the fecal microbiota, such as an increased relative abundance of the genus Flavonifractor, which is known to be inversely associated with obesity. Correlations between eCBome mediators and other potentially beneficial taxa were also observed, thus reinforcing the hypothesis of the existence of a link between the eCBome and the gut microbiome in obesity.
Highlights
Non-communicable diseases, such as heart disease, stroke, cancer, chronic respiratory diseases and diabetes, are the leading causes of mortality in the world [1]
To reproductive-aged women living with overweight and obesity produced important changes in the plasma eCBome, which may be indicative of potential beneficial effects at the level of hyperphagia, insulin sensitivity and inflammation
While we did not see any significant correlation between eCBome mediators and the appetite and satiety measures, here we did not assess measures of insulin sensitivity or chronic inflammation
Summary
Non-communicable diseases, such as heart disease, stroke, cancer, chronic respiratory diseases and diabetes, are the leading causes of mortality in the world [1]. Due to the multifactorial nature of obesity—encompassing hereditary factors, ethnic differences, environment and individual behavior—efficient strategies to regulate energy intake that lead to significant and sustained weight loss are not well defined, and, to date, no clear non-surgical solution has been developed [4,5]. Pharmaceutical drugs, such as orlistat, which is a potent and specific inhibitor of intestinal lipases that can reduce body weight with variable efficacy, can lead to gastrointestinal, hepatic and kidney injuries [6,7]. Increasing efforts are aimed at developing novel strategies, including active natural ingredients and functional foods, which could facilitate appetite control, to promote favorable changes in body energy stores and exert long-term benefits on metabolic health [6]
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