Obesity as a Condition Determined by Food Addiction: Should Brain Endocannabinoid System Alterations Be the Cause and Its Modulation the Solution?

Ceglia, Marialuisa de; Decara, Juan; Gaetani, Silvana; Fonseca, Fernando Rodrı́guez de

doi:10.3390/ph14101002

Cited by 14 publications

(9 citation statements)

References 204 publications

(294 reference statements)

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“…There are other regulatory mechanisms such as the endocannabinoid system [ 81 ] and endogenous opioid [ 82 ]; however, they will not be considered further in the present work.…”

Section: The Hunger–satiety Pathwaysmentioning

confidence: 99%

Could Naringenin Participate as a Regulator of Obesity and Satiety?

et al. 2023

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Obesity is a serious health problem worldwide, since it is associated with multiple metabolic disorders and complications such as cardiovascular disease, type 2 diabetes, fatty liver disease and overall metabolic dysfunction. Dysregulation of the hunger–satiety pathway, which includes alterations of central and peripheral signaling, explains some forms of obesity by favoring hyperphagia and weight gain. The present work comprehensively summarizes the mechanisms by which naringenin (NAR), a predominant flavanone in citrus fruits, could modulate the main pathways associated with the development of obesity and some of its comorbidities, such as oxidative stress (OS), inflammation, insulin resistance (IR) and dyslipidemia, as well as the role of NAR in modulating the secretion of enterohormones of the satiety pathway and its possible antiobesogenic effect. The results of multiple in vitro and in vivo studies have shown that NAR has various potentially modulatory biological effects against obesity by countering IR, inflammation, OS, macrophage infiltration, dyslipidemia, hepatic steatosis, and adipose deposition. Likewise, NAR is capable of modulating peptides or peripheral hormones directly associated with the hunger–satiety pathway, such as ghrelin, cholecystokinin, insulin, adiponectin and leptin. The evidence supports the use of NAR as a promising alternative to prevent overweight and obesity.

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“…There are other regulatory mechanisms such as the endocannabinoid system [ 81 ] and endogenous opioid [ 82 ]; however, they will not be considered further in the present work.…”

Section: The Hunger–satiety Pathwaysmentioning

confidence: 99%

Could Naringenin Participate as a Regulator of Obesity and Satiety?

et al. 2023

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“…Furthermore, both obesity and food addiction have been linked to deficiencies in the ECSs in various regions of the brain. There is an interaction of ECS, DA, leptin, orexin, and ghrelin, considering that the lateral hypothalamus is an area with high expression of CB1 receptors, and in pathological obesity, it is associated with increased expression of CB1, which reinforces the high consumption of CB1 highly palatable food (De Ceglia et al, 2021). Despite many biological similarities between food and drug consumption, also significant differences have been reported.…”

Section: Neurobiology and Animal Modelsmentioning

confidence: 99%

Food Addiction

et al. 2022

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Food addiction is associated with dysfunctions in the reward circuit, such as hyperresponsiveness during the exposure to high-calorie flavors in overweight and obese individuals. Similar to drug addiction, there is also impaired self-regulatory control supported by deregulation of the frontostriatal circuit. The inclusion of validated measures of food addiction in clinical research, such as the Yale Food Addiction Scale, has increased the understanding of the clinical utility of this concept. Furthermore, food addiction, eating disorders, and obesity are interrelated. Thus, it is important to recognize food addiction among individuals affected by obesity and candidates for bariatric surgery (ie, preoperative and postoperative assessment). In this context, it has been reported that food addiction may impede weight loss and increase the likelihood of regaining weight when associated with personality traits such as neuroticism and impulsiveness, which are also related to mood disorders, anxiety, and addictive behaviors.

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“…Despite the studies suggesting a role for ECS in the development of obesity, no effective therapy targeting this system has been approved, because of behavioral side effects observed both in preclinical and clinical research (de Ceglia et al, 2021). Indeed, different components of ECS show a unique role in modulating the onset and offset of anxiety induced by stress response (Bedse et al, 2015(Bedse et al, , 2017Lisboa et al, 2017;Maldonado et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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Obesity as a Condition Determined by Food Addiction: Should Brain Endocannabinoid System Alterations Be the Cause and Its Modulation the Solution?

Cited by 14 publications

References 204 publications

Could Naringenin Participate as a Regulator of Obesity and Satiety?

Could Naringenin Participate as a Regulator of Obesity and Satiety?

Food Addiction

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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