Work

Mature adipocytes lack functional Aryl Hydrocarbon Receptor – a study investigating its role in diet-induced obesity in mice

Year: 2026

Type: article

Abstract: 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.

Source: Wellcome Open Research

DOI: 10.12688/wellcomeopenres.25201.2

Authors: Julia Vlachaki Walker, Benjamin Wiggins, Alice Burke, Marian Dore, Alessandro Sardini, Chris Schiering

Institutions: King's College London, Imperial College London, The Francis Crick Institute

Language: English

Topic: Adipokines, Inflammation, and Metabolic Diseases

Subfield: Epidemiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $1,128