The DOI matches its Crossref record; 60 of the 60 references it cites were found in a registry or an index.
Peripheral Cannabinoid-1 Receptor Inverse Agonism Reduces Obesity by Reversing Leptin Resistance
Open accessAbstract
SUMMARY Obesity-related leptin resistance manifests in loss of leptin’s ability to reduce appetite and increase energy expenditure. Obesity is also associated with increased activity of the endocannabinoid system, and CB1 receptor (CB1R) inverse agonists reduce body weight and the associated metabolic complications, although adverse neuropsychiatric effects halted their therapeutic development. Here we show that in mice with diet-induced obesity (DIO), the peripherally restricted CB1R inverse agonist JD5037 is equieffective with its brain-penetrant parent compound in reducing appetite, body weight, hepatic steatosis, and insulin resistance, even though it does not occupy central CB1R or induce related behaviors. Appetite and weight reduction by JD5037 are mediated by resensitizing DIO mice to endogenous leptin through reversing the hyperleptinemia by decreasing leptin expression and secretion by adipocytes and increasing leptin clearance via the kidney. Thus, inverse agonism at peripheral CB1R not only improves cardiometabolic risk in obesity but has antiobesity effects by reversing leptin resistance.
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Cites
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“, 2006), and CB1R inverse Cel agonists reduce body weight and improve metabolic abnormalities in obese subjects (Addy et al., 2008; Despres et al., 2005), although adverse neuropsychiatric effects halted their therapeutic development.”
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Self-citationObesity and leptin resistance: distinguishing cause from effect
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βAR Signaling Required for Diet-Induced Thermogenesis and Obesity Resistance
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Cited by
Endocannabinoid signaling at the periphery: 50 years after THC
Maccarrone, M., Bab, I., Bíró, T., Cabral, G. A., Dey, S. K., Di Marzo, V., Konje, J. C., Kunos, G., Mechoulam, R., Pacher, P., et al. (2015) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2015.02.008 · Cited by 646
Self-citationThe Endocannabinoid System in Energy Homeostasis and the Etiopathology of Metabolic Disorders
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High-resolution crystal structure of the human CB1 cannabinoid receptor
Shao, Z., Yin, J., Chapman, K., Grzemska, M., Clark, L., Wang, J., & Rosenbaum, D. M. (2016) · Nature · doi:10.1038/nature20613 · Cited by 419
Modulating the endocannabinoid system in human health and disease – successes and failures
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Metadata
- Authors
- Tam, J., Cinar, R., Liu, J., Godlewski, G., Wesley, D., Jourdan, T., Szanda, G., Mukhopadhyay, B., Chedester, L., Liow, J.-S., Innis, R. B., Cheng, K., Rice, K. C., Deschamps, J. R., Chorvat, R. J., McElroy, J. F., & Kunos, G.
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2012-08
- Volume
- 16
- Issue
- 2
- Pages
- 167-179
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2094409327
- Cited by
- 356
- References
- 60
- FWCI
- 19.41
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Tam, J., Cinar, R., Liu, J., Godlewski, G., Wesley, D., Jourdan, T., Szanda, G., Mukhopadhyay, B., Chedester, L., Liow, J.-S., Innis, R. B., Cheng, K., Rice, K. C., Deschamps, J. R., Chorvat, R. J., McElroy, J. F., & Kunos, G. (2012). Peripheral Cannabinoid-1 Receptor Inverse Agonism Reduces Obesity by Reversing Leptin Resistance. Cell Metabolism. https://doi.org/10.1016/j.cmet.2012.07.002
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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