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Updated: Jul 1, 2026
Isolation and Culturing of Primary Murine Adipocytes from Lean and Obese Mice
Published on: January 24, 2025
Mature adipocytes lack functional Aryl Hydrocarbon Receptor - a study investigating its role in diet-induced obesity
Julia Vlachaki Walker1,2,3, Benjamin Wiggins1,2,4, Alice Burke1,2
1Faculty of Medicine, Imperial College London Institute of Clinical Sciences, London, England, UK.
Background:
Despite rising awareness and advances in the field, the prevalence of obesity continues to increase. Current weight-loss treatments are often ineffective long-term, and some are associated with serious side effects. For this reason, alternative pathways need to be explored in order to identify novel pharmacological targets for the treatment of obesity. In this study, we aim to investigate the role of the ligand-activated transcription factor, aryl hydrocarbon receptor (AHR), in the development of obesity and metabolic syndrome.
Methods & Results:
Using global and adipocyte-specific Ahr knock-out mouse models, we show that even though global Ahr deletion has some protective effects from diet-induced obesity and metabolic syndrome, adipocyte-specific deletion of Ahr has no effect. Furthermore, using a variety of techniques to isolate mature adipocytes, such as flotation, in-vitro differentiation, and translating ribosome affinity purification, we show no evidence that Ahr is expressed in mature white adipocytes. Finally, using single-cell RNA sequencing on cells from a Cyp1a1 fate reporter mouse line, in which eYFP can be used as a readout of AHR activation, we show that the AHR pathway is active in adipose stem and precursor cells. Using bulk RNA sequencing on adipocyte precursors stimulated with an AHR ligand in-vitro , we show evidence suggesting that Ahr may be involved in the control of adipocyte differentiation.
Conclusions:
Our study indicates that Ahr may play an important role in adipocyte precursors, particularly in the initiation of adipocyte differentiation. We suggest that further investigation into this mechanism may be important to fully elucidate AHR's effects in obesity.
Insights
The aryl hydrocarbon receptor (AHR) pathway is active in adipose stem cells, suggesting a role in controlling obesity and adipocyte differentiation. Further research into AHR may reveal new obesity treatments.
Area of Science:
- Metabolic research
- Obesity research
- Pharmacology
Background:
- Obesity prevalence is increasing globally.
- Current weight-loss treatments have limitations and side effects.
- Novel pharmacological targets for obesity are needed.
Purpose of the Study:
- Investigate the role of the aryl hydrocarbon receptor (AHR) in obesity and metabolic syndrome.
- Determine AHR's function in adipocytes and precursor cells.
Main Methods:
- Utilized global and adipocyte-specific Ahr knock-out mouse models.
- Employed techniques like flotation and RNA sequencing to analyze adipocytes and precursors.
- Used single-cell RNA sequencing to track AHR pathway activation in adipose stem cells.
Main Results:
- Global Ahr deletion offered some protection against diet-induced obesity.
- Adipocyte-specific Ahr deletion showed no effect on obesity.
- AHR pathway is active in adipose stem and precursor cells, not mature adipocytes.
- Evidence suggests AHR influences adipocyte differentiation.
Conclusions:
- AHR plays a significant role in adipocyte precursors, particularly in initiating differentiation.
- Further investigation of AHR mechanisms is crucial for understanding its role in obesity.
