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Adipocytes cell's immune response makes obesity worse

Thu, 06/11/2020 - 14:32
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Scientists at Cincinnati Children's and the University of Cincinnati College of Medicine have outlined the details of new cellular process that shows how adipocytes’ (fat calls) immune response worsens obesity. The team reports that type I interferons, a class of substances produced by immune cells also are produced by fat cells called adipocytes. These interferons drive a constant low-level, chronic immune response that amplifies "vigour” to a cycle of inflammation within white adipose tissue (WAT).

In the study, ‘Type I interferon sensing unlocks dormant adipocyte inflammatory potential’, published in Nature Communications, the authors found that this inflammation appears to drive a cascade of cellular responses that promotes obesity-related disease, especially type 2 diabetes and non-alcoholic fatty liver disease (NAFLD).

"Our novel study reveals how Type I Interferon sensing by adipocytes uncovers their dormant inflammatory potential and exacerbates obesity-associated metabolic derangements,” said Dr Senad Divanovic, corresponding author and a researcher in the Division of Immunobiology at Cincinnati Children's. “Further, our findings highlight a previously underappreciated role for adipocytes as a contributor to the overall inflammation in obesity.”

Long known as a major risk factor for type 2 diabetes, NAFLD, cardiovascular disease and diverse cancers, obesity also has been linked with elevated susceptibility and risk of developing serious complications to infection. Obesity also was an independent risk factor for severity and mortality in the 2009 H1N1 influenza pandemic, and is a risk for hospital admission and poor outcomes among those infected in the current COVID-19 pandemic.

Many studies have shown that obesity is much more complicated than simply eating too much or not getting enough exercise. Previous work has shown that obesity also reflects the outcome of various disruptions to how the body converts food into energy for our cells.

However, only recently have scientists begun to suspect that these excess calories could reshape fat cell behaviour to affect the immune system.

The study shows how type 1 interferons operate along an axis of interaction with IFNa receptors (IFNAR) to trigger a vicious cycle of inflammation. Among the effects: changes in expression of several genes associated with inflammation, glycolysis and fatty acid production.

For example, mice fed an obesity-inducing diet displayed an augmented type I IFN signature including increases in Ifnb1, Ifnar1, Oas1a, and Isg15 gene expression, the team reported.

Importantly, many of the metabolic changes documented in mice were found to be conserved in human adipocytes.

This activity was unexpected, because until now most scientists have studied type 1 interferons in relation to viral infections and immune cell function.

"Our observations suggest that the type I Interferon axis can alter adipocyte core inflammatory programming to converge them closer to that of an inflammatory immune cell. Additionally, type I Interferons modify the metabolic circuit of adipocytes, which to our knowledge is the first depiction of immune-mediated modulation of adipocyte core metabolism," added Divanovic.

Further investigation continues into the specific mechanisms that type I Interferons employ to modify adipocyte core metabolism. In addition, researchers continue to study the full extent of how adipocytes can "mimic" inflammatory immune cell capabilities. Beyond diabetes and NAFLD, the interplay between obesity and the immune system appears to increase risk of preterm birth and may reduce the body's ability to fight off infections, including viruses such as COVID-19.

"These findings directly impact an extensive number of patients, both adult and paediatric," concluded Divanovic says.

To access this paper, please click here