Insulin differentially modulates the peripheral endocannabinoid system in human subcutaneous abdominal adipose tissue from lean and obese individuals
Abstract
Human obesity has been associated with a dysregulation of the peripheral and adipose tissue (AT) endocannabinoid system (ES). The aim of this study was to elucidate the acute in vivo effects of insulin on gene expression of the cannabinoid type 1 (CB-1) and type 2 (CB-2) receptors, as well as of the fatty acid amide hydrolase (FAAH) in the sc abdominal adipose tissue (SCAAT). Nine lean (L) and 9 obese (OB), but otherwise healthy males were studied in the fasting state and during a euglycemic hyperinsulinemic clamp (40 mU/m2 * min(-1)). SCAAT biopsies were obtained at baseline and after 270 min of i.v. maintained hyperinsulinemia. The basal SCAAT gene expression pattern revealed an upregulation of the FAAH in the OB (p=0.03 vs L), whereas similar CB-1 and CB-2 mRNA levels were seen. Following hyperinsulinemia, the FAAH mRNA levels significantly increased approximately 2-fold in the L (p=0.01 vs baseline) but not in the OB. In contrast, insulin failed to significantly change both the adipose CB-1 and CB-2 gene expression. Finally, the FAAH gene expression positively correlated with the fasting serum insulin concentration (r 0.66; p=0.01), whereas an inverse association with the whole-body glucose disposal (r -0.58; p<0.05) was seen. Taken together, these first time observations demonstrate that the ES-related genes in the SCAAT differentially respond to hyperinsulinemia in lean/insulin-sensitive and in obese/insulin-resistant individuals. We suggest that insulin may play a key role in the obesity-linked dysregulation of the adipose ES at the gene level.
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Lean males subjected to hyperinsulinemia show a 2-fold increase in FAAH mRNA expression whereas obese males subjected to the same conditions failed to show similar alterations.
“Lean males subjected to hyperinsulinemia show a 2-fold increase in FAAH mRNA expression whereas obese males subjected to the same conditions failed to show similar alterations in gene expression.111”
From Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside (2009) · cites this paper as [111]
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- Authors
- Murdolo, G., Kempf, K., Hammarstedt, A., Herder, C., Smith, U., & Jansson, P. A.
- Affiliations
- University of Gothenburg (SE)
- Deutsches Diabetes-Zentrum e.V. (DE)
- Corresponding author
- Murdolo, G.
- Venue
- Journal of Endocrinological Investigation
- Published
- 2007-09
- Volume
- 30
- Issue
- 8
- Pages
- RC17-RC21
- ISSN
- 0391-4097 (ISSN-L)
- 1720-8386
- OpenAlex
- W2098174994
- Cited by
- 58
- References
- 19
- Citations by year
- 2026: 2 · 2024: 1 · 2021: 2 · 2020: 3 · 2019: 3 · 2018: 2 · 2017: 1 · 2016: 2 · 2015: 2 · 2014: 2 · 2013: 5 · 2012: 4
- FWCI
- 4.88
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Journal of Endocrinological Investigation (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- insulin, endocannabinoid system, subcutaneous abdominal fat, obesity, hyperinsulinemia, CB1 receptor, CB2 receptor, fatty acid amide hydrolase, gene expression, insulin resistance, glucose disposal
- MeSH terms
- Adult, Biopsy, Body Weight, Diabetes Mellitus, Type 2, Fasting, Humans, Hyperinsulinism, Hypoglycemic Agents, Insulin, Male, Obesity, Up-Regulation, Gene Expression, Receptor, Cannabinoid, CB1, Receptor, Cannabinoid, CB2, Subcutaneous Fat, Abdominal
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