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Fat fights back

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Is fat a immune organ, vital for host defense? In 2015, an important study in Science suggested that fat has an important immune function that prevents invasion by pathogens

From Dermal adipocytes protect against invasive Staphylococcus aureus skin infection:

“Adipocytes have been suggested to be immunologically active, but their role in host defense is unclear. We observed rapid proliferation of preadipocytes and expansion of the dermal fat layer after infection of the skin by Staphylococcus aureus. Impaired adipogenesis resulted in increased infection as seen in Zfp423nur12 mice or in mice given inhibitors of peroxisome proliferator–activated receptor γ. This host defense function was mediated through the production of cathelicidin antimicrobial peptide from adipocytes because cathelicidin expression was decreased by inhibition of adipogenesis, and adipocytes from Camp−/− mice lost the capacity to inhibit bacterial growth. Together, these findings show that the production of an antimicrobial peptide by adipocytes is an important element for protection against S. aureus infection of the skin.”

This is in line the idea that fat provides a barrier function necessary for microbial containment. It is not an inert depot of stored energy. Fat has a critical role to play during infection. Fat defends us and deserves our respect.

In December of last year, a research team led by Yasmine Belkaid showed in the journal Cell that white adipose tissue is a storage site for memory T cells that are critical for antimicrobial defense, particularly when we are re-exposed to pathogens. They write: white adipose tissue from previously infected mice was sufficient to protect uninfected mice from lethal pathogen challenge.

Separately, Kredel et al. argued that fat in the abdomen has a similar antimicrobial role in the gut that walls off gut bacteria. They argue that the hormones produced by fat cells, called adipokines, are necessary to block translocation and frank invasion by gut bacteria. They also suggest that “creeping fat” in the guts of patients with Crohn disease functions as a physical barrier to gut microbes that would otherwise escape containment in the intestine.

Along similar lines, Hegde and Dhurandar wrote a review on the infection-fat link and the antimicrobial effects of fat in Clinical Microbiology and Infection:

“In addition to the immune cells of adipose tissue, evidence is emerging that even pre-adipocytes and adipocytes are likely to interact with invading microbes.

If visceral fat has a host defense function, it makes sense that its removal would not be helpful and might in fact increase the risk of septic death.

It is worth pointing out that the concept of a host defense function of abdominal fat is not new. In 1906, Rutherford Morison termed visceral fat in the omentum “the abdominal policeman” for its role in preventing sepsis. Morison wrote:

Abscesses in connexion with the vermiform appendix are locked up, and pus is generally prevented from escaping into the general peritoneal cavity by the omentum.

This observation is in line with the hypothesis that the main function of visceral fat (abdominal fat) is to contain and prevent the spread of gut bacteria into sterile sites. Not only does containment occur anatomically as described by Morison, but at a microscopic level as well. Visceral fat is an immunological organ that provides fuel for the immune system, generates pro-inflammatory cytokine mobilization, and houses phagocytic cells that mop up bacteria that escape the gut.

If fat functions as a barrier, and has an infection fighting role, it might explain decreased mortality among the overweight, known as the obesity paradox. 

Appreciating the defensive function of fat also explains why belly fat can be caused by unhealthy microbial communities in the microbiome, otherwise known as dysbiosis.

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In other words, accumulating fat is a predictable response, not just to excess calories, but also to microbial threats. It’s immune function is a two-edged sword that can protect us, and also leads to smoldering inflammation that has harmful long term effects on health and longevity.

Copyright © Joe Alcock MD

Learn about the evolutionary tradeoffs of fat this summer at the 4th annual meeting of ISEMPH – The International Society for Evolution, Medicine and Public Health in beautiful Park City, Utah. Abstract submissions are now open!

Categories: Uncategorized

Joe Alcock

Emergency Physician, Educator, Researcher, interested in the microbiome, evolution, and medicine

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