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Activation of the Peripheral Endocannabinoid System in Human Obesity
Open accessAbstract
Obesity is the main risk factor for the development of type 2 diabetes. Activation of the central endocannabinoid system increases food intake and promotes weight gain. Blockade of the cannabinoid type 1 (CB-1) receptor reduces body weight in animals by central and peripheral actions; the role of the peripheral endocannabinoid system in human obesity is now being extensively investigated. We measured circulating endocannabinoid concentrations and studied the expression of CB-1 and the main degrading enzyme, fatty acid amide hydrolase (FAAH), in adipose tissue of lean (n = 20) and obese (n = 20) women and after a 5% weight loss in a second group of women (n = 17). Circulating levels of anandamide and 1/2-arachidonoylglycerol were increased by 35 and 52% in obese compared with lean women (P < 0.05). Adipose tissue mRNA levels were reduced by -34% for CB-1 and -59% for FAAH in obese subjects (P < 0.05). A strong negative correlation was found between FAAH expression in adipose tissue and circulating endocannabinoids. Circulating endocannabinoids and CB-1 or FAAH expression were not affected by 5% weight loss. The expression of CB-1 and FAAH was increased in mature human adipocytes compared with in preadipocytes and was found in several human tissues. Our findings support the presence of a peripheral endocannabinoid system that is upregulated in human obesity.
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“and this effect is likely to result from downregulation of FAAH gene expression, an effect which has also been observed in adipocytes sampled from obese women.110”
From Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside (2009) · cites this paper as [110]
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Cited by
Sorted by citations
The Endocannabinoid System as an Emerging Target of Pharmacotherapy
Pacher, P., Bátkai, S., & Kunos, G. (2006) · Pharmacological Reviews · doi:10.1124/pr.58.3.2 · Cited by 2,077
“In a study involving 40 women (Engeli et al., 2005), circulating levels of anandamide and 2-AG were significantly increased in 20 obese versus 20 lean subjects, and remained elevated after a 5% diet-induced weight reduction.”
BackgroundInfluentialSelf-citationAdipose tissue dysfunction in obesity, diabetes, and vascular diseases
Hajer, G. R., van Haeften, T. W., & Visseren, F. L. J. (2008) · European Heart Journal · doi:10.1093/eurheartj/ehn387 · Cited by 1,410
The Emerging Role of the Endocannabinoid System in Endocrine Regulation and Energy Balance
Pagotto, U., Marsicano, G., Cota, D., Lutz, B., & Pasquali, R. (2005) · Endocrine Reviews · doi:10.1210/er.2005-0009 · Cited by 891
“In such a context, a recent work (60) showed increased circulating levels of AEA and 2-AG in obese women when compared with a lean control group.”
BackgroundInfluentialThe endocannabinoid system links gut microbiota to adipogenesis
Muccioli, G. G., Naslain, D., Bäckhed, F., Reigstad, C. S., Lambert, D. M., Delzenne, N. M., & Cani, P. D. (2010) · Molecular Systems Biology · doi:10.1038/msb.2010.46 · Cited by 691
“On the other hand, obesity is also characterised by greater eCB system tone, that is increased eCB plasma levels, altered expression of the cannabinoid receptor 1 (CB 1 mRNA) and increased eCB levels in adipose tissues”
BackgroundInfluentialMatias, I., Gonthier, M., Orlando, P., Martiadis, V., PETROCELLIS, L. D., Cervino, C., Petrosino, S., Hoareau, L., Festy, F., Pasquali, R., et al. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-2679 · Cited by 654
Metadata
- Authors
- Engeli, S., Böhnke, J., Feldpausch, M., Gorzelniak, K., Janke, J., Bátkai, S., Pacher, P., Harvey-White, J., Luft, F. C., Sharma, A. M., & Jordan, J.
- Affiliations
- Helios Hospital Berlin-Buch (DE)
- Franz Volhard Clinical Research Center, Charité Campus Buch, and HELIOS Klinikum Berlin, Berlin, Germany
- Laboratory of Physiologic Studies, National Institute on Alcohol Abuse & Alcoholism, National Institutes of Health, Bethesda, Maryland
- National Institutes of Health (US)
- McMaster University (CA)
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2005-10-01
- Volume
- 54
- Issue
- 10
- Pages
- 2838-2843
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- PMC
- PMC2228268
- OpenAlex
- W2162112945
- Cited by
- 686
- References
- 37
- Citations by year
- 2026: 11 · 2025: 14 · 2024: 20 · 2023: 19 · 2022: 20 · 2021: 30 · 2020: 29 · 2019: 24 · 2018: 30 · 2017: 30 · 2016: 15 · 2015: 31 · 2014: 29 · 2013: 29 · 2012: 33
- FWCI
- 38.06
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
- Funders
- Sanofi
- Bundesministerium für Bildung und Forschung
- National Institutes of Health
- National Institute on Alcohol Abuse and Alcoholism (Z01AA000375)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- obesity, cannabinoid type 1 receptor, fatty acid amide hydrolase, anandamide, 2-arachidonoylglycerol, adipose tissue, weight loss, human adipocytes, type 2 diabetes risk
- MeSH terms
- Fatty Acid Amide Hydrolases, Adipose Tissue, Amidohydrolases, Arachidonic Acids, Body Composition, Female, Glycerides, Humans, Middle Aged, Obesity, RNA, Messenger, Weight Loss, Gene Expression, Body Mass Index, Linear Models, Postmenopause, Reverse Transcriptase Polymerase Chain Reaction, Receptor, Cannabinoid, CB1, Polyunsaturated Alkamides, Cannabinoid Receptor Modulators, Endocannabinoids
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