Cannabinoid Receptor 2 as Antiobesity Target: Inflammation, Fat Storage, and Browning Modulation

Rossi, Francesca; Bellini, Giulia; Luongo, Livio; Manzo, Iolanda; Tolone, Salvatore; Tortora, Chiara; Bernardo, Maria Ester; Grandone, Anna; Conforti, Antonella; Docimo, Ludovico; Nobili, Brúno; Perrone, Laura; Locatelli, Franco; Maione, Sabatino; Giudice, Emanuele Miraglia del

doi:10.1210/jc.2015-4381

Cited by 55 publications

(44 citation statements)

References 41 publications

(32 reference statements)

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“…In contrast, CB-2 agonists can suppress obesity, steatohepatitis and can additionally protect the liver from ischemic reperfusion injury. Further, CB-2 agonist decrease hepatic immune cells infiltration, kupffer cell activation, oxidative stress, hepatic injury and fibrogenesis [39–42]. Taken together, our novel observations and previous findings suggest that CB-2 agonist and hemp which has a higher CBD might offer more protection from NAFLD [43,44].…”

Section: Discussionsupporting

confidence: 65%

Cannabis use is associated with reduced prevalence of non-alcoholic fatty liver disease: A cross-sectional study

et al. 2017

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Cannabis use is associated with reduced prevalence of obesity and diabetes mellitus (DM) in humans and mouse disease models. Obesity and DM are a well-established independent risk factor for non-alcoholic fatty liver disease (NAFLD), the most prevalent liver disease globally. The effects of cannabis use on NAFLD prevalence in humans remains ill-defined. Our objective is to determine the relationship between cannabis use and the prevalence of NAFLD in humans. We conducted a population-based case-control study of 5,950,391 patients using the 2014 Healthcare Cost and Utilization Project (HCUP), Nationwide Inpatient Survey (NIS) discharge records of patients 18 years and older. After identifying patients with NAFLD (1% of all patients), we next identified three exposure groups: non-cannabis users (98.04%), non-dependent cannabis users (1.74%), and dependent cannabis users (0.22%). We adjusted for potential demographics and patient related confounders and used multivariate logistic regression (SAS 9.4) to determine the odds of developing NAFLD with respects to cannabis use. Our findings revealed that cannabis users (dependent and non-dependent) showed significantly lower NAFLD prevalence compared to non-users (AOR: 0.82[0.76–0.88]; p<0.0001). The prevalence of NAFLD was 15% lower in non-dependent users (AOR: 0.85[0.79–0.92]; p<0.0001) and 52% lower in dependent users (AOR: 0.49[0.36–0.65]; p<0.0001). Among cannabis users, dependent patients had 43% significantly lower prevalence of NAFLD compared to non-dependent patients (AOR: 0.57[0.42–0.77]; p<0.0001). Our observations suggest that cannabis use is associated with lower prevalence of NAFLD in patients. These novel findings suggest additional molecular mechanistic studies to explore the potential role of cannabis use in NAFLD development.

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Section: Discussionsupporting

confidence: 65%

Cannabis use is associated with reduced prevalence of non-alcoholic fatty liver disease: A cross-sectional study

et al. 2017

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“…Here we have mostly reviewed information on the roles of anandamide, 2-AG and CB 1 R in energy balance; however, it should be mentioned that some evidence suggests an involvement for CB 2 R in energy balance (139,140,141) and that compounds structurally related to endocannabinoids but unable to bind to CB 1 R, like oleoylethanolamide (OEA), actually oppose endocannabinoids effects on energy balance (142). Besides, endocannabinoids do not exclusively exert their biological functions through CBRs, however they can also bind transient receptor potential vanilloid 1 (TRPV1) (143) and the nuclear receptor peroxisome proliferatoractivated receptor γ (PPARγ) (56).…”

Section: Discussionmentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: Endocannabinoids and metabolism: past, present and future

Simon

Cota

2017

European Journal of Endocrinology

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The endocannabinoid system (ECS), including cannabinoid type 1 and type 2 receptors (CB 1 R and CB 2 R), endogenous ligands called endocannabinoids and their related enzymatic machinery, is known to have a role in the regulation of energy balance. Past information generated on the ECS, mainly focused on the involvement of this system in the central nervous system regulation of food intake, while at the same time clinical studies pointed out the therapeutic efficacy of brain penetrant CB 1 R antagonists like rimonabant for obesity and metabolic disorders. Rimonabant was removed from the market in 2009 and its obituary written due to its psychiatric side effects. However, in the meanwhile a number of investigations had started to highlight the roles of the peripheral ECS in the regulation of metabolism, bringing up new hope that the ECS might still represent target for treatment. Accordingly, peripherally restricted CB 1 R antagonists or inverse agonists have shown to effectively reduce body weight, adiposity, insulin resistance and dyslipidemia in obese animal models. Very recent investigations have further expanded the possible toolbox for the modulation of the ECS, by demonstrating the existence of endogenous allosteric inhibitors of CB 1 R, the characterization of the structure of the human CB 1 R, and the likely involvement of CB 2 R in metabolic disorders. Here we give an overview of these findings, discussing what the future may hold in the context of strategies targeting the ECS in metabolic disease.

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“…Cannabis can act through hepatic endocannabinoid system (ECS) receptors CB-1 and CB-2, which have been revealed to have opposing effects of pro-and anti-steatotic/fibrotic/inflammatory, respectively, in the liver. 20,21,29,34,35 After alcohol exposure in mice, hepatic stellate cells secrete 2-arachidonoylglycerol (2-AG), an endocannabinoid, which activates hepatocyte CB-1 receptors to drive steatosis and hepatitis. 36 Conversely, the administration of cannabidiol (CBD), a CB-2 receptor agonist, suppressed intracellular inflammatory signals and increase autophagy, 32 which functions in cellular lipid homeostasis, 37,38 and may consequently prevents steatohepatitis.…”

Section: Discussionmentioning

confidence: 99%

Cannabis use is associated with reduced prevalence of progressive stages of alcoholic liver disease

Adejumo

Ajayi

Adegbala

et al. 2018

Liver International

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Background Abusive alcohol use has well‐established health risks including causing liver disease (ALD) characterized by alcoholic steatosis (AS), steatohepatitis (AH), fibrosis, cirrhosis (AC) and hepatocellular carcinoma (HCC). Strikingly, a significant number of individuals who abuse alcohol also use Cannabis, which has seen increased legalization globally. While cannabis has demonstrated anti‐inflammatory properties, its combined use with alcohol and the development of liver disease remain unclear. Aim The aim of this study was to determine the effects of cannabis use on the incidence of liver disease in individuals who abuse alcohol. Methods We analysed the 2014 Healthcare Cost and Utilization Project‐Nationwide Inpatient Sample (NIS) discharge records of patients 18 years and older, who had a past or current history of abusive alcohol use (n = 319 514). Using the International Classification of Disease, Ninth Edition codes, we studied the four distinct phases of progressive ALD with respect to three cannabis exposure groups: non‐cannabis users (90.39%), non‐dependent cannabis users (8.26%) and dependent cannabis users (1.36%). We accounted for the complex survey sampling methodology and estimated the adjusted odds ratio (AOR) for developing AS, AH, AC and HCC with respect to cannabis use (SAS 9.4). Results Our study revealed that among alcohol users, individuals who additionally use cannabis (dependent and non‐dependent cannabis use) showed significantly lower odds of developing AS, AH, AC and HCC (AOR: 0.55 [0.48‐0.64], 0.57 [0.53‐0.61], 0.45 [0.43‐0.48] and 0.62 [0.51‐0.76]). Furthermore, dependent users had significantly lower odds than non‐dependent users for developing liver disease. Conclusions Our findings suggest that cannabis use is associated with a reduced incidence of liver disease in alcoholics.

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Cannabinoid Receptor 2 as Antiobesity Target: Inflammation, Fat Storage, and Browning Modulation

Abstract: CB2 receptor is a novel pharmacological target that should be considered for obesity.

Cited by 55 publications

References 41 publications

Cannabis use is associated with reduced prevalence of non-alcoholic fatty liver disease: A cross-sectional study

Cannabis use is associated with reduced prevalence of non-alcoholic fatty liver disease: A cross-sectional study

MECHANISMS IN ENDOCRINOLOGY: Endocannabinoids and metabolism: past, present and future

Cannabis use is associated with reduced prevalence of progressive stages of alcoholic liver disease

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