A novel peripheral cannabinoid receptor 1 antagonist, <scp>BPR0912</scp>, reduces weight independently of food intake and modulates thermogenesis

Hsiao, Wen-Chi; Shia, Kak‐Shan; Wang, Y.-T.; Yeh, Yen-Nan; Chang, C. P.; Lin, Ying‐Ting; Chen, P.-H.; Wu, Chien-Huang; Chao, Yu‐Sheng; Hung, Ming‐Shiu

doi:10.1111/dom.12447

Cited by 34 publications

(22 citation statements)

References 50 publications

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“…CB1R blockade also increases BAT UCP-1 expression [22,72]. Consistently, rimonabant treatment increases energy expenditure and BAT temperature [72,73], and Hsiao et al [74] demonstrated that chronic peripheral inhibition of CB1R by BPR0912 induced UCP-1 expression in BAT of mice and elevated core body temperature, indicating increased thermogenic activity of BAT. Importantly, BAT can be visualized in rats using radioactive PET ligands with high affinity for CB1R, thereby demonstrating its dense presence in the tissue in vivo [75].…”

Section: Cb2r Signaling In Watmentioning

confidence: 71%

Regulation of Adipose Tissue Metabolism by the Endocannabinoid System

Eenige

Stelt

Rensen

et al. 2018

Trends in Endocrinology & Metabolism

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White adipose tissue (WAT) stores excess energy as triglycerides, and brown adipose tissue (BAT) is specialized in dissipating energy as heat. The endocannabinoid system (ECS) is involved in a broad range of physiological processes and is increasingly recognized as a key player in adipose tissue metabolism. High ECS tonus in the fed state is associated with a disadvantageous metabolic phenotype, and this has led to a search for pharmacological strategies to inhibit the ECS. In this review we present recent developments that cast light on the regulation of adipose tissue metabolism by the ECS, and we discuss novel treatment options including the modulation of endocannabinoid synthesis and breakdown enzymes.

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Section: Cb2r Signaling In Watmentioning

confidence: 71%

Regulation of Adipose Tissue Metabolism by the Endocannabinoid System

Eenige

Stelt

Rensen

et al. 2018

Trends in Endocrinology & Metabolism

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“…CB1R antagonist rimonabant (SR141716) was previously in clinical use with strong efficacy for weight loss, but was withdrawn because of serious psychiatric adverse effects (14). Recently, novel CB1R antagonists, which act strictly peripherally, have been found to activate BAT in rodents, inducing lipolysis and lipid oxidation, thus improving metabolism (15,16). Activation of BAT via CB1R antagonism without harmful centrally mediated adverse effects could be one way to improve metabolic disease and combat obesity in humans (17).…”

mentioning

confidence: 99%

Cannabinoid Type 1 Receptors Are Upregulated During Acute Activation of Brown Adipose Tissue

et al. 2018

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Activating brown adipose tissue (BAT) could provide a potential approach for the treatment of obesity and metabolic disease in humans. Obesity is associated with upregulation of the endocannabinoid system, and blocking the cannabinoid type 1 receptor (CB1R) has been shown to cause weight loss and to decrease cardiometabolic risk factors. These effects may be mediated partly via increased BAT metabolism, since there is evidence that CB1R antagonism activates BAT in rodents. To investigate the significance of CB1R in BAT function, we quantified the density of CB1R in human and rodent BAT using the positron emission tomography radioligand [F]FMPEP- and measured BAT activation in parallel with the glucose analog [F]fluorodeoxyglucose. Activation by cold exposure markedly increased CB1R density and glucose uptake in the BAT of lean men. Similarly, β3-receptor agonism increased CB1R density in the BAT of rats. In contrast, overweight men with reduced BAT activity exhibited decreased CB1R in BAT, reflecting impaired endocannabinoid regulation. Image-guided biopsies confirmed CB1R mRNA expression in human BAT. Furthermore, CB1R blockade increased glucose uptake and lipolysis of brown adipocytes. Our results highlight that CB1Rs are significant for human BAT activity, and the CB1Rs provide a novel therapeutic target for BAT activation in humans.

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“…Verty triglycerides, and hepatic triglycerides were observed with both compounds, but compared to rimonabant, BPR0912 raised fatty acid oxidation-related gene expression and thermogenesis more significantly (Hsiao et al 2015). In summary, activation of CB1 receptors contributes to increased appetite, suppressed energy expenditure, and when deranged, obesity.…”

Section: Appetite and Energy Expenditurementioning

confidence: 88%

Cannabinoid signaling in health and disease

Lü

Anderson

2017

Can. J. Physiol. Pharmacol.

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Cannabis sativa has long been used for medicinal purposes. To improve safety and efficacy, compounds from C. sativa were purified or synthesized and named under an umbrella group as cannabinoids. Currently, several cannabinoids may be prescribed in Canada for a variety of indications such as nausea and pain. More recently, an increasing number of reports suggest other salutary effects associated with endogenous cannabinoid signaling including cardioprotection. The therapeutic potential of cannabinoids is therefore extended; however, evidence is limited and mechanisms remain unclear. In addition, the use of cannabinoids clinically has been hindered due to pronounced psychoactive side effects.This review provides an overview on the endocannabinoid system, including known physiological roles, and conditions in which cannabinoid receptor signaling has been implicated.

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A novel peripheral cannabinoid receptor 1 antagonist, BPR0912, reduces weight independently of food intake and modulates thermogenesis

Cited by 34 publications

References 50 publications

Regulation of Adipose Tissue Metabolism by the Endocannabinoid System

Regulation of Adipose Tissue Metabolism by the Endocannabinoid System

Cannabinoid Type 1 Receptors Are Upregulated During Acute Activation of Brown Adipose Tissue

Cannabinoid signaling in health and disease

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