Exploring the circadian influence of immune cells on metabolic health and fat storage

Trinity College DublinNov 6 2024

Recent research reveals that the immune system interacts with the body's internal clock, influencing both fat storage and temperature regulation. These insights carry substantial implications for individuals with irregular work, eating, or sleep patterns driven by the demands of modern life.

The key finding – that an immune molecule within adipose (fat) tissue, known as interleukin-17A (IL-17A), plays a regulatory role in fat storage – holds significant therapeutic potential for addressing obesity, preventing wasting, and mitigating other metabolic disorders. By targeting this molecule, drug developers may gain a valuable new pathway for creating treatments aimed at these conditions.

Circadian rhythms are biological processes that operate on a 24-hour cycle, ensuring that key biological functions occur at specific times of day to synchronise the body with external environmental cues. The most prominent example is the sleep-wake cycle, which aligns with the natural light-dark cycle of the sun.

The immune system operates on a circadian rhythm, priming the body to anticipate and combat infections at specific times of day. Recently, research has highlighted an additional role of immune cell circadian rhythms in sustaining tissue integrity and function – most notably in the gut, where specialised cells deliver metabolic signals that optimise nutrient absorption during feeding periods.

In a recent study led by Professor Lydia Lynch and published in leading international journal Nature, researchers report that key immune cells – γδ T cells, which produce IL-17A – exhibit elevated expression of "molecular clock" genes. These genes play a crucial role in regulating efficient fat storage, a process significantly influenced by a stable and well-regulated circadian rhythm.

Mice missing molecular clock genes in these cells exhibited impaired fat processing and storage, while whole-body metabolic analyses further revealed disrupted metabolic rhythms and irregular core body temperature regulation.

Prof. Lydia Lynch, Visiting Researcher at Trinity College Dublin's School of Biochemistry and Immunology and Professor of Molecular Biology at the Ludwig Cancer Research Institute, Princeton University, highlighted the significance of this research. She said: "Modern life frequently disrupts natural sleep patterns, whether due to shift work, prolonged exposure to blue light from screens, or the constant connectivity of mobile devices. Many of us, despite feeling fatigued, find ourselves scrolling through social media far longer than intended each night.

"Our discovery that an immune molecule in adipose tissue regulates fat storage is particularly compelling, as it offers potential therapeutic avenues for addressing obesity and preventing metabolic diseases-;especially in populations affected by shift work. 

"Obesity is an increasingly prevalent condition with extensive, detrimental effects on health and wellbeing, and it places a substantial burden on healthcare systems worldwide."

This discovery opens numerous avenues for further research. A key question is whether T cells help regulate circadian rhythms in other tissues and, if so, whether this similarly impacts those tissues' rhythms in essential ways."

Aaron Douglas, Postdoctoral Fellow, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute

"Particularly intriguing are T cells located near the brain, as their activity may significantly influence higher-order functions like learning and memory, or even impact brain regions involved in whole-body metabolism and temperature regulation."