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Targeting Gut Inflammation Can Reduce Insulin Resistance?



sharma-obesity-adipose-tissue-macrophageWith all of the recent interest in the gut microbiota as a mediator of systemic inflammation and metabolic disease, it was only a matter of time before researchers would begin targeting pro-inflammatory pathways in the gut to change metabolism.

A proof-of-principle, that this is indeed possible, is presented by Helen Luck and colleagues from the University of Toronto in a paper published in Cell Metabolism.

Using mice models, the researchers not only show that a high-fat diet can alter the gut immune system but also that the chronic phenotypic pro-inflammatory shift in bowel lamina propria immune cell populations is reduced in genetically altered mice that lack beta7 integrin-deficient mice (Beta7null), a driver of gut inflammatory response.

Further more, treatment of high-fat-fed normal mice with the local gut anti-inflammatory agent 5-aminosalicyclic acid (5-ASA), reverses bowel inflammation and improves metabolic parameters including insulin resistance (although it had no effect on body weight).

These beneficial effects are are associated with reduced gut permeability and endotoxemia as well as decreased visceral adipose tissue inflammation.

Moreover, treatment with ASA also improved antigen-specific tolerance to luminal antigens.

Thus, as the authors conclude,

“…the mucosal immune system affects multiple pathways associated with systemic insulin resistance and represents a novel therapeutic target in this disease.”

Clearly gut inflammation both in relationship to gut microbiota as well as response to dietary factors is likely to be a hot topic in obesity and metabolic research for the foreseeable future.

@DrSharma
Edmonton, AB

3 Comments

  1. Can you just clarify – don’t quite understand the third para above – where you say that this research showed that ‘a high-fat diet can alter the gut immune system’ – was the effect a positive (ie, healthy) or not? Trying to work out if you are saying the high fat diet created the inflammation that the anti inflammatory agents then reduced (ie, did the high fat diet create the problem or was it part of the solution?).

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    • The HFD created the problem – this was reduced/prevented by treating with the anti-inflammatory agents.

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      • What fats are being consumed and what level indicates ‘high’?

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