Rimonabant improves cholesterol, insulin resistance and markers of non-alcoholic fatty liver in morbidly obese patients: a retrospective cohort study

Wierzbicki, Anthony S.; Pendleton, Scott; McMahon, Zofia; Dar, A.; Oben, Jude A.; Crook, Martin; Botha, Abrie

doi:10.1111/j.1742-1241.2011.02683.x

Cited by 15 publications

(6 citation statements)

References 9 publications

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“…Although not completely elucidated, the mechanisms by which cannabinoids affect peripheral metabolism via these receptors have been studied previously y; the cannabinoid type 1 receptor antagonist, rimonabant, was found to improve insulin sensitivity in wild-type mice, but not in adiponectin knockout mice, suggesting that adiponectin at least partially mediates the improvement in insulin sensitivity; adiponectin has been reported to improve insulin sensitivity. This rimonabant-induced improvement in insulin resistance has been confirmed in human studies [33][34][35].…”

Section: Cannabis and Diabetessupporting

confidence: 54%

Diabetes and Cannabis: Myth or Reality

Gunturiz¹,

Chaparro²

2018

Cardiol Vasc Res

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Medical marijuana is one of the fastest growing industries in the United States and in developing countries such as Colombia, but research into the benefits of the plant is a global issue. Although there are studies that present evidence that people who take or smoke it, may have a lower susceptibility to diabetes due to metabolic acceleration caused by the plant in the body, with this review we intend to show that the evidence obtained is not is still enough to think that marijuana could be a treatment for diabetes or other non-transmissible chronic diseases. This presumption is due to the lack of knowledge of its adverse effects and the consequences of cannabis use on the severity of these pathologies. Additionally, more clinical studies are required to demonstrate that marijuana activates the balance between metabolism and glucose and therefore demonstrate that this "medicinal" plant can help patients who already have the disease to decrease their dependence on insulin.

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Section: Cannabis and Diabetessupporting

confidence: 54%

Diabetes and Cannabis: Myth or Reality

Gunturiz¹,

Chaparro²

2018

Cardiol Vasc Res

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“…The hepatic expression of the CB 1 R is upregulated in DIO and murine models of fatty liver [ 3 , 4 , 7 ]. In fact, its presence in hepatocytes is crucial for the development of NAFLD [ 4 ]; therefore, centrally acting and peripherally restricted CB 1 R antagonists were found to be efficacious in ameliorating hepatic steatosis in both humans [ 9 , 51 ] and animals [ 6 , 8 , 52 ]. To elucidate the underlying molecular mechanism by which the CB 1 R contributes to NAFLD, we used an unbiased approach utilizing NPP analysis to identify multiple genes that display a conservation pattern across phylogenetic clades similar to those of the CB 1 R. In doing so, we hypothesized that genes that are coevolved with the CB 1 R are functionally linked [ 13 ].…”

Section: Discussionmentioning

confidence: 99%

Reversal of diet-induced hepatic steatosis by peripheral CB1 receptor blockade in mice is p53/miRNA-22/SIRT1/PPARα dependent

Azar

Udi

Drori

et al. 2020

Molecular Metabolism

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Objective The endocannabinoid (eCB) system is increasingly recognized as being crucially important in obesity-related hepatic steatosis. By activating the hepatic cannabinoid-1 receptor (CB 1 R), eCBs modulate lipogenesis and fatty acid oxidation. However, the underlying molecular mechanisms are largely unknown. Methods We combined unbiased bioinformatics techniques, mouse genetic manipulations, multiple pharmacological, molecular, and cellular biology approaches, and genomic sequencing to systematically decipher the role of the hepatic CB 1 R in modulating fat utilization in the liver and explored the downstream molecular mechanisms. Results Using an unbiased normalized phylogenetic profiling analysis, we found that the CB 1 R evolutionarily coevolves with peroxisome proliferator-activated receptor-alpha (PPARα), a key regulator of hepatic lipid metabolism. In diet-induced obese (DIO) mice, peripheral CB 1 R blockade (using AM6545) induced the reversal of hepatic steatosis and improved liver injury in WT, but not in PPARα −/− mice. The antisteatotic effect mediated by AM6545 in WT DIO mice was accompanied by increased hepatic expression and activity of PPARα as well as elevated hepatic levels of the PPARα-activating eCB-like molecules oleoylethanolamide and palmitoylethanolamide. Moreover, AM6545 was unable to rescue hepatic steatosis in DIO mice lacking liver sirtuin 1 (SIRT1), an upstream regulator of PPARα. Both of these signaling molecules were modulated by the CB 1 R as measured in hepatocytes exposed to lipotoxic conditions or treated with CB 1 R agonists in the absence/presence of AM6545. Furthermore, using microRNA transcriptomic profiling, we found that the CB 1 R regulated the hepatic expression, acetylation, and transcriptional activity of p53, resulting in the enhanced expression of miR-22, which was found to specifically target SIRT1 and PPARα. Conclusions We provide strong evidence for a functional role of the p53/miR-22/SIRT1/PPARα signaling pathway in potentially mediating the antisteatotic effect of peripherally restricted CB 1 R blockade.

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“…Although the exact mechanism underlying the positive modulatory activity of cannabinoids on peripheral metabolism has not yet been fully understood, the activity of these compounds on CB receptors of peripheral organs may somehow explicate the answer. In this context, it has been shown that administration of rimonabant, a CB 1 antagonist, was together with a significant improvement in the sensitivity of normal mice to insulin, proposing that adiponectin may be the responsible molecule in the improvement of sensitivity to insulin ( 23 ). This finding has also been established in human studies.…”

Section: Discussionmentioning

confidence: 99%

A Phase I Randomized, Double-blind, Placebo-controlled Study on Efficacy and Safety Profile of a Sublingually Administered Cannabidiol /Delta 9-tetrahydrocannabidiol (10: 1) Regimen in Diabetes Type 2 Patients

et al. 2023

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: The current study aimed to evaluate the safety profile and efficacy of a cannabis-based sublingual spray, CBDEX10® (containing 100 µg cannabidiol and 10 µg Δ9-tetrahydrocannabinol per puff; CBD/Δ9-THC 10:1), in improving lipid profile and glycemic state of the diabetic patients. Fifty diabetic patients were randomly allocated to the treatment (n = 25; receiving two puffs of CBDEX10® twice daily) or the control groups (n = 25; receiving two puffs of placebo). The primary endpoint of the study was to evaluate the efficacy of the CBDEX10® adjunctive therapy in improving the lipid profile and glycemic state of diabetic patients; the secondary endpoint was to assess the safety profile and tolerability of the spray. A statistically significant decline in total cholesterol [estimated treatment difference (ETD) = −19.73 mg/dL; P < 0.05], triglyceride (ETD = −27.84 mg/dL; P < 0.01), LDL-C (ETD = −5.37 mg/dL; P < 0.01), FBS (ETD = −12 mg/dL; P < 0.01), HbA1c (ETD = −0.21 mg/dL; P < 0.01) and insulin secretion (ETD = -5.21 mIU/L; P < 0.01) was observable in the patients treated with CBDEX10® at the end of the 8-week treatment period. Regarding safety, the mentioned adjunctive regimen was well, and there were no serious or severe adverse effects. Overall, CBDEX10® sublingual spray could be a new therapeutic agent for lipid and glycemic control in diabetic patients.

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Rimonabant improves cholesterol, insulin resistance and markers of non-alcoholic fatty liver in morbidly obese patients: a retrospective cohort study

Cited by 15 publications

References 9 publications

Diabetes and Cannabis: Myth or Reality

Diabetes and Cannabis: Myth or Reality

Reversal of diet-induced hepatic steatosis by peripheral CB1 receptor blockade in mice is p53/miRNA-22/SIRT1/PPARα dependent

A Phase I Randomized, Double-blind, Placebo-controlled Study on Efficacy and Safety Profile of a Sublingually Administered Cannabidiol /Delta 9-tetrahydrocannabidiol (10: 1) Regimen in Diabetes Type 2 Patients

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