Abundant evidence now connects over-nutrition and obesity to a chronic low-grade inflammatory state manifested not only by cells of the immune system but also, notably, by adipocytes, a process collectively known as 'meta-inflammation'. In The Journal of Clinical Investigation, Rosen and colleagues investigate the role of the pro-inflammatory transcription factor IRF3 in meta-inflammation. The abundance of IRF3 is greater in adipose tissue of both obese humans and mice fed a high-fat diet. Similarly, IRF3 activity, as measured by transcription of its target genes, is also greater in mice fed a high-fat diet. IRF3-deficient mice and their adipocytes show improved metabolic parameters, such as diminished insulin resistance, when the mice are fed a high-fat diet. These mice also show greater adaptive thermogenesis, probably a consequence of enhanced browning of their white adipose tissue. IRF3 therefore acts as an adipocyte-intrinsic factor that mediates pro-inflammatory signals and opposes browning.
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AGING MEDICINE (2019)