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Updated: May 27, 2026
Differentiation and Imaging of Brown Adipocytes from the Stromal Vascular Fraction of Interscapular Adipose Tissue from Newborn Mice
Published on: February 3, 2023
Effect of the Cannabinoid Receptor-1 antagonist SR141716A on human adipocyte inflammatory profile and differentiation
Ravi Murumalla1, Karima Bencharif1, Lydie Gence1
1GEICO, Groupe d'Etude sur l'Inflammation et l'Obésité Chronique, Université de La Réunion, plateforme CYROI, 15 avenue René Cassin, 97715 Saint-Denis Messag Cedex, France.
Background:
Obesity is characterized by inflammation, caused by increase in proinflammatory cytokines, a key factor for the development of insulin resistance. SR141716A, a cannabinoid receptor 1 (CB1) antagonist, shows significant improvement in clinical status of obese/diabetic patients. Therefore, we studied the effect of SR141716A on human adipocyte inflammatory profile and differentiation.
Methods:
Adipocytes were obtained from liposuction. Stromal vascular cells were extracted and differentiated into adipocytes. Media and cells were collected for secretory (ELISA) and expression analysis (qPCR). Triglyceride accumulation was observed using oil red-O staining. Cholesterol was assayed by a fluorometric method. 2-AG and anandamide were quantified using isotope dilution LC-MS. TLR-binding experiments have been conducted in HEK-Blue cells.
Results:
In LPS-treated mature adipocytes, SR141716A was able to decrease the expression and secretion of TNF-a. This molecule has the same effect in LPS-induced IL-6 secretion, while IL-6 expression is not changed. Concerning MCP-1, the basal level is down-regulated by SR141716A, but not the LPS-induced level. This effect is not caused by a binding of the molecule to TLR4 (LPS receptor). Moreover, SR141716A restored adiponectin secretion to normal levels after LPS treatment. Lastly, no effect of SR141716A was detected on human pre-adipocyte differentiation, although the compound enhanced adiponectin gene expression, but not secretion, in differentiated pre-adipocytes.
Conclusion:
We show for the first time that some clinical effects of SR141716A are probably directly related to its anti-inflammatory effect on mature adipocytes. This fact reinforces that adipose tissue is an important target in the development of tools to treat the metabolic syndrome.
Insights
SR141716A, a cannabinoid receptor 1 antagonist, reduces inflammation in mature human fat cells, improving adiponectin levels. This suggests adipose tissue is a key target for metabolic syndrome treatments.
Area of Science:
- Metabolic Syndrome Research
- Adipose Tissue Biology
- Inflammation and Immunity
Background:
- Obesity is linked to inflammation and increased pro-inflammatory cytokines, contributing to insulin resistance.
- Cannabinoid receptor 1 (CB1) antagonist SR141716A shows promise in improving clinical outcomes for obese/diabetic patients.
Purpose of the Study:
- To investigate the impact of SR141716A on the inflammatory profile of human adipocytes.
- To assess the effect of SR141716A on human adipocyte differentiation.
Main Methods:
- Human adipocytes were differentiated from stromal vascular cells obtained via liposuction.
- Inflammatory markers (TNF-α, IL-6, MCP-1, adiponectin) were analyzed using ELISA and qPCR.
- Lipid accumulation, cholesterol, and endocannabinoids were quantified; TLR4 binding was assessed.
Main Results:
- SR141716A decreased TNF-α expression/secretion and IL-6 secretion in LPS-treated adipocytes.
- SR141716A modulated MCP-1 and restored adiponectin secretion following LPS treatment.
- SR141716A did not affect pre-adipocyte differentiation but enhanced adiponectin gene expression in differentiated cells.
Conclusions:
- SR141716A exerts anti-inflammatory effects directly on mature human adipocytes, likely contributing to its clinical benefits.
- These findings highlight adipose tissue as a critical therapeutic target for metabolic syndrome.
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