Endocannabinoids and the Gut-Brain Control of Food Intake and Obesity

DiPatrizio, Nicholas V.

doi:10.3390/nu13041214

Cited by 30 publications

(29 citation statements)

References 121 publications

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“…Although evidence of the possible action of these bacteria through the modulation of the gut–brain axis is scarce [ 305 , 306 , 307 ], preclinical studies demonstrated that A. muciniphila administration to obese mice increases the intestinal production of the endocannabinoid, 2-arachidonoylglycerol (2-AG); and the endocannabinoid analogue, oleoylglycerol (2-OG) [ 305 ]. These ligands can modulate the secretory function of L cells and, theoretically, the activity of vagal afferents [ 308 , 309 ].…”

Section: Tackling Obesity With Gut Microbes Mediating In Gut–brain Communicationmentioning

confidence: 99%

The Microbiota and the Gut–Brain Axis in Controlling Food Intake and Energy Homeostasis

Romaní-Pérez

Bullich-Vilarrubias

López-Almela

et al. 2021

IJMS

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Obesity currently represents a major societal and health challenge worldwide. Its prevalence has reached epidemic proportions and trends continue to rise, reflecting the need for more effective preventive measures. Hypothalamic circuits that control energy homeostasis in response to food intake are interesting targets for body-weight management, for example, through interventions that reinforce the gut-to-brain nutrient signalling, whose malfunction contributes to obesity. Gut microbiota–diet interactions might interfere in nutrient sensing and signalling from the gut to the brain, where the information is processed to control energy homeostasis. This gut microbiota–brain crosstalk is mediated by metabolites, mainly short chain fatty acids, secondary bile acids or amino acids-derived metabolites and subcellular bacterial components. These activate gut–endocrine and/or neural-mediated pathways or pass to systemic circulation and then reach the brain. Feeding time and dietary composition are the main drivers of the gut microbiota structure and function. Therefore, aberrant feeding patterns or unhealthy diets might alter gut microbiota–diet interactions and modify nutrient availability and/or microbial ligands transmitting information from the gut to the brain in response to food intake, thus impairing energy homeostasis. Herein, we update the scientific evidence supporting that gut microbiota is a source of novel dietary and non-dietary biological products that may beneficially regulate gut-to-brain communication and, thus, improve metabolic health. Additionally, we evaluate how the feeding time and dietary composition modulate the gut microbiota and, thereby, the intraluminal availability of these biological products with potential effects on energy homeostasis. The review also identifies knowledge gaps and the advances required to clinically apply microbiome-based strategies to improve the gut–brain axis function and, thus, combat obesity.

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Section: Tackling Obesity With Gut Microbes Mediating In Gut–brain Communicationmentioning

confidence: 99%

The Microbiota and the Gut–Brain Axis in Controlling Food Intake and Energy Homeostasis

Romaní-Pérez

Bullich-Vilarrubias

López-Almela

et al. 2021

IJMS

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“…The endocannabinoid (eCB) system is expressed in cells throughout the body and consists of lipid signaling molecules including the primary eCBs, 2-arachidonoyl-sn-glycerol (2-AG) and arachidonoyl ethanolamide (anandamide, AEA), their biosynthetic and degradative enzymes, and the cannabinoid receptors [cannabinoid receptor subtype-1 (CB 1 R) and subtype-2 (CB 2 R), and possibly others] (Devane et al, 1987(Devane et al, , 1992Kaminski et al, 1992;Mechoulam et al, 1995;Piomelli, 2003;Pertwee, 2015; see Figure 1). ECBs are produced upon cellular activation and synthesized from lipid precursors found in the plasma membrane of cells (DiPatrizio, 2021). 2-AG and AEA activate the same cannabinoid receptors; however, their biosynthesis and degradation are controlled by distinct enzymatic pathways.…”

Section: Introductionmentioning

confidence: 99%

“…2-AG and AEA activate the same cannabinoid receptors; however, their biosynthesis and degradation are controlled by distinct enzymatic pathways. Diacylglycerol lipase (DGL) hydrolyzes distinct diacylglycerol precursors and generates 2-AG and other related monoacylglycerol (MAG) species including 2docosohexaenoylglycerol (2-DG), 2-pamitoylglycerol (2-PG), 2oleoylglycerol (2-OG), and 2-linoleoylglycerol (2-LG) (Ghafouri et al, 2004;Alexander and Kendall, 2007;DiPatrizio, 2021). These MAGs are degraded via monoacylglycerol lipase (MGL) into free fatty acids and glycerol (DiPatrizio, 2021).…”

Section: Introductionmentioning

confidence: 99%

“…Diacylglycerol lipase (DGL) hydrolyzes distinct diacylglycerol precursors and generates 2-AG and other related monoacylglycerol (MAG) species including 2docosohexaenoylglycerol (2-DG), 2-pamitoylglycerol (2-PG), 2oleoylglycerol (2-OG), and 2-linoleoylglycerol (2-LG) (Ghafouri et al, 2004;Alexander and Kendall, 2007;DiPatrizio, 2021). These MAGs are degraded via monoacylglycerol lipase (MGL) into free fatty acids and glycerol (DiPatrizio, 2021). Furthermore, alpha/beta hydrolase domain containing-6 (ABHD6) and -12 (ABHD12) are capable of degrading MAGs, including 2-AG, and contribute to total MAG degradation in the brain (Blankman et al, 2007;Marrs et al, 2010;DiPatrizio, 2021).…”

Section: Introductionmentioning

confidence: 99%

“…These MAGs are degraded via monoacylglycerol lipase (MGL) into free fatty acids and glycerol (DiPatrizio, 2021). Furthermore, alpha/beta hydrolase domain containing-6 (ABHD6) and -12 (ABHD12) are capable of degrading MAGs, including 2-AG, and contribute to total MAG degradation in the brain (Blankman et al, 2007;Marrs et al, 2010;DiPatrizio, 2021).…”

Section: Introductionmentioning

confidence: 99%

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UPLC-MS/MS Method for Analysis of Endocannabinoid and Related Lipid Metabolism in Mouse Mucosal Tissue

et al. 2021

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The endocannabinoid system is expressed in cells throughout the body and controls a variety of physiological and pathophysiological functions. We describe robust and reproducible UPLC-MS/MS-based methods for analyzing metabolism of the endocannabinoids, 2-arachidonoyl-sn-glycerol and arachidonoyl ethanolamide, and related monoacylglycerols (MAGs) and fatty acid ethanolamides (FAEs), respectively, in mouse mucosal tissues (i.e., intestine and lung). These methods are optimized for analysis of activity of the MAG biosynthetic enzyme, diacylglycerol lipase (DGL), and MAG degradative enzymes, monoacylglycerol lipase (MGL) and alpha/beta hydrolase domain containing-6 (ABHD6). Moreover, we describe a novel UPLC-MS/MS-based method for analyzing activity of the FAE degradative enzyme, fatty acid amide hydrolase (FAAH), that does not require use of radioactive substrates. In addition, we describe in vivo pharmacological methods to inhibit MAG biosynthesis selectively in the mouse small-intestinal epithelium. These methods will be useful for profiling endocannabinoid metabolism in rodent mucosal tissues in health and disease.

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Anxiety associated with palatable food withdrawal is reversed by the selective FAAH inhibitor PF‐3845: A regional analysis of the contribution of endocannabinoid signaling machinery

Ceglia

Bonaventura

Romano

et al. 2023

Intl J Eating Disorders

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Objective Consumption of energy‐dense palatable “comfort” food can alleviate stress and negative emotions, while abrupt withdrawal from a palatable diet can worsen these symptoms, causing difficulties with adherence to weight‐loss diets. Currently, no pharmacological treatment is effective for obesity‐related anxiety, so we investigated the endocannabinoid system (ECS), and specifically the fatty acid amide hydrolase (FAAH), as an interesting emerging target in this context because of its key role in the regulation of both energy homeostasis and emotional behavior. Methods Rats were subjected to exposure and subsequent abstinence from a palatable cafeteria diet. During abstinence period, rats were treated with the selective FAAH inhibitor PF‐3845 (10 mg/kg; intraperitoneal administration every other day). Results Abstinent rats displayed an anxiogenic‐like behavior and changes in the proteins of ECS signaling machinery in brain areas involved both in anxiety and food intake regulation. In particular, withdrawal caused a reduction of the expression of cannabinoid receptors in the nucleus accumbens and of enzymes diacylglycerol lipase alpha and monoacylglycerol lipase (MAGL) in the amygdala. Pharmacological inhibition of FAAH exerted an anxiolytic‐like effect in abstinent animals and increased both MAGL expression in amygdala and CB2 expression in prefrontal cortex. Discussion Overall, our results suggest that emotional disturbances associated with dieting are coupled with region‐specific alterations in the cerebral expression of the ECS and that the enhancement of the endocannabinoid signaling by FAAH inhibition might represent a novel pharmacological strategy for the treatment of anxiety related to abstinence from palatable food. Public Significance The present study focused on evaluating the role of the endocannabinoid system in modulating withdrawal from naturally rewarding activities that have an impact on mood, such as feeding. The variations observed in the emotional behavior of abstinent rats was linked to neuroadaptations of the ECS in specific brain areas.

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Endocannabinoids and the Gut-Brain Control of Food Intake and Obesity

Cited by 30 publications

References 121 publications

The Microbiota and the Gut–Brain Axis in Controlling Food Intake and Energy Homeostasis

The Microbiota and the Gut–Brain Axis in Controlling Food Intake and Energy Homeostasis

UPLC-MS/MS Method for Analysis of Endocannabinoid and Related Lipid Metabolism in Mouse Mucosal Tissue

Anxiety associated with palatable food withdrawal is reversed by the selective FAAH inhibitor PF‐3845: A regional analysis of the contribution of endocannabinoid signaling machinery

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