Completed Diabetes, Hormones & Metabolism Lungs & Breathing

Dissecting the role of aryl hydrocarbon receptor in thermogenic adipose tissue

In plain English

AI plain-English summary

Brown fat burns calories to generate heat, and a protein called the aryl hydrocarbon receptor (AHR) may act as a molecular switch that controls this process. Obesity affects hundreds of millions of people worldwide, and existing treatments remain limited. Brown adipose tissue (BAT) burns energy rather than storing it, and adults with more active BAT tend to have lower body weight and better metabolic health. But no one knows exactly how dietary compounds—such as those found in vegetables or produced by gut bacteria—might trigger BAT activity. This project aims to fill that gap by testing whether natural molecules that bind to AHR can safely rev up brown fat. If the research succeeds, it could open a new route to treating obesity and metabolic syndrome using dietary supplements or food-based compounds rather than synthetic drugs. That would shift the focus from calorie restriction to calorie burning, potentially offering a simpler, more accessible intervention. However, this is fundamental science. The immediate goal is to understand how AHR regulates thermogenesis at the molecular level—identifying which genes it switches on in specific cell types. Similar fundamental work on brown fat a decade ago led to the discovery that adults retain active BAT, which now underpins an entire field of metabolic research. Deeper knowledge of AHR’s role could eventually lead to targeted therapies, but that remains years away.

View original technical description
The obesity crisis has reached epidemic proportions and represents one of the most significant global public health challenges. The recent discovery of energy dissipating brown adipose tissue (BAT) in adult humans has raised the possibility of targeting BAT for the treatment of obesity. Indeed, studies in humans and mice have demonstrated an inverse relationship of BAT activity with obesity and metabolic syndrome. I propose to explore the potential of natural dietary compounds that are sensed by the aryl hydrocarbon receptor (AHR) as novel inducers of BAT activity. I will identify the physiological role of AHR in thermogenesis and utilize conditional gene-targeting approaches to define cell-autonomous functions of AHR in specific cell-types within BAT. Importantly, I will determine whether dietary AHR ligands, such as phytochemicals and microbiota metabolites, can induce the thermogenic activity of BAT, promote energy expenditure and improve metabolic disease in the context of obesity. To elucidate the mechanisms by which AHR modulates thermogenic programs, I will identify its direct transcriptional targets in specific cell-types using ChIP-seq and RNA-seq. Together, these studies will provide important insights into the regulation of thermogenesis by specific dietary factors and may facilitate the use of natural AHR ligands for the treatment of obesity.

View the original record at the funder ↗

Researchers

Chris Schiering (EPMC Awardee)

Related Research

Grants with similar aims, by meaning.

Dissecting thermogenesis by brown adipose tissue and skeletal muscle in lean and obese subjects
Delineating the role of aryl hydrocarbon receptor signalling in obesity.
New players in human BAT differentiation and activation: a human PSC-derived BAT approach combined with state of the art genome engineering and –omics based methodologies
Activating brown adipose tissue to treat atherosclerosis and cardiovascular disease
Delineation of a brain circuit regulating energy expenditure to impact body weight

Original classification

Sir Henry Dale Fellowship

Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.