Fat as an immune organ

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Zhang and colleagues recently published an important study in Science suggesting that fat has an important immune function and prevents invasion by pathogens, entitled Dermal adipocytes protect against invasive Staphylococcus aureus skin infection.

From the abstract:

“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 with a hypothesis put forward in a previous post, that fat provides a barrier function during infection, preventing systemic invasion by pathogens.

Along similar lines, Hegde and Dhurandar recently 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.

A previous study by Wang and colleagues in the journal Obesity described a link between obesity and the risk of sepsis. In that study, only the morbidly obese had a higher risk of sepsis. Moderately obese persons did fine. That result is in line with expectations of the hypothesis that visceral fat has a host defense function. Moderate obesity, in fact, might protect against certain infections, which may explain decreased mortality among the overweight, known as the obesity paradox. These lines of evidence imply that fat has a function beyond energy storage.

If visceral fat has a host defense function, it makes sense that its removal would not improve inflammation 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 comports with the hypothesis that the main function of visceral 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 acts as 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 further research substantiates a host defense function of fat, it will add an adaptive lens with which to view the complex web of metabolic and inflammatory changes in obesity. Appreciating the physiologic function of fat, and the selective pressure induced by gut microbes, will be critical to discovering new ways of treating obesity and related diseases.

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