How body fat affects your immune system

Weighty Matters: How body fat affects your immune system

Every organism survives thanks to two critical systems: metabolic and immune. The metabolic system ensures our bodies have sufficient energy (i.e., calories) to defend itself against periods of little or no food. The fat tissue typifies this system, insofar as it is the primary reservoir of calories that the body can lean on when food is less abundant. The immune system, in contrast, provides a different defense, with macrophages (and other immune cells) protecting the body from outside attackers in the form of infectious pathogens (e.g., bacteria or viruses).

These two essential defenses, one against starvation and the other against invasion, don’t operate in separate battle fields—rather, they coordinate their efforts to ensure a healthy body wins the war. When the metabolic system is working well, which I’d most simply define as being insulin sensitive, the immune system works well. Unfortunately, these two systems sometimes experience “friendly fire” and unintentionally work against each other.

In rare instances, when there is not enough fuel (e.g., starvation), the body runs out of body fat and immunity shuts down, making the body much more susceptible to serious, life-threatening infection [1]. After all, immune cells need fuel to defend the body. However, far more commonly in modern times, people suffer from excess energy and too much fat. This over-abundance of energy actually stimulates the immune system to fight infections that aren’t actually there—a state called “subclinical inflammation” [2]. In addition to explaining numerous fat-related disorders, such as insulin resistance and heart disease [2], excess body fat may be the single most important detriment to having a functioning immune system.

Fat (sometimes) starts the fight

When fat cells become hypertrophic (grow too large), they begin releasing free fatty acids. In addition to being an energy source (if perhaps too much), these fatty acids also have an immune effect—they stimulate macrophages to become more inflammatory, producing and releasing more pro-inflammatory proteins called cytokines [3].

Beyond its ability to activate inflammatory cells like macrophages with its released fatty acids, fat cells directly make things worse by acting like macrophages—they start making their own cytokines [4]. Once again, this is a matter of size—when the fat cells get too big (i.e., hypertrophy) they get mean and start releasing cytokines. One of the most abundantly produced and problematic cytokines goes beyond inflammation by directly altering the blood. This cytokine, called PAI-1, makes the blood clot more readily, increasing the risk of strokes, which is a potentially lethal consequence of infections [5].

Body fat is home for (some) infections

Fat cells store more than just fat. In fact, fat cells can store all kinds of things, including certain industrial pollutants [6, 7]. Unfortunately, they can also provide a home for harmful and infectious invaders. But the virus has to find a way into the cell first. In order for a virus to enter a cell, it needs a receptor—basically, a doorway that it’s able to slip through. In some instances, depending on the virus, fat cells have more receptors (i.e., doorways) for the virus than almost any other cell in the body, making it the preferred cellular home [8]. Of course, this is compounded by having even more fat cells (i.e., being fatter), making fat an even more welcoming host!

Once in the fat cell, a virus takes things even further; they turn their new homes into factories. Once infected with a virus, a fat cell begins producing and releasing more and more of the virus to infect more cells throughout the body [9].

These aspects of fat cells housing and producing viruses are a large reason why excess body fat is such a consistent and significant risk factor for serious viral infections [9]. In fact, with the recent viral flu season wrapping up, we’ve learned that almost 80% of all of hospital admissions were attributed to excess body fat [10].

Make dietary fat work for you

Thankfully, not all fats create problems for our immune systems—some actually help. Lauric acid, the primary fat in coconut oil, is known to elicit anti-microbial effects, potentially facilitating the immune system [11]. Furthermore, lauric acid may directly prevent viruses from replicating [12]. Also, omega-3 fats are metabolized into molecules called “resolvins”, which directly reduce inflammation [13].

Take-away thoughts

Having too much body fat compromises immune function, increasing inflammation and making the body more susceptible to infections. Now, more than ever, having a robust immune system is essential. We can help it work better by maintaining or improving our metabolic health with proper dietary changes.

References

1 Ritz, B. W. and Gardner, E. M. (2006) Malnutrition and energy restriction differentially affect viral immunity. The Journal of nutrition. 136, 1141-1144
2 Pradhan, A. (2007) Obesity, metabolic syndrome, and type 2 diabetes: inflammatory basis of glucose metabolic disorders. Nutrition reviews. 65, S152-156
3 Namgaladze, D. and Brune, B. (2016) Macrophage fatty acid oxidation and its roles in macrophage polarization and fatty acid-induced inflammation. Biochimica et biophysica acta. 1861, 1796-1807
4 Hotamisligil, G. S., Shargill, N. S. and Spiegelman, B. M. (1993) Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science. 259, 87-91
5 Loskutoff, D. J. and Samad, F. (1998) The adipocyte and hemostatic balance in obesity: studies of PAI-1. Arteriosclerosis, thrombosis, and vascular biology. 18, 1-6
6 Hao, C. J., Cheng, X. J., Xia, H. F. and Ma, X. (2012) The endocrine disruptor diethylstilbestrol induces adipocyte differentiation and promotes obesity in mice. Toxicol Appl Pharmacol. 263, 102-110
7 Fernandez, M. F., Arrebola, J. P., Taoufiki, J., Navalon, A., Ballesteros, O., Pulgar, R., Vilchez, J. L. and Olea, N. (2007) Bisphenol-A and chlorinated derivatives in adipose tissue of women. Reprod Toxicol. 24, 259-264
8 Al-Benna, S. (2020) Association of high level gene expression of ACE2 in adipose tissue with mortality of COVID-19 infection in obese patients. Obes Med. 19, 100283
9 Desruisseaux, M. S., Nagajyothi, Trujillo, M. E., Tanowitz, H. B. and Scherer, P. E. (2007) Adipocyte, adipose tissue, and infectious disease. Infect Immun. 75, 1066-1078
10 Pennington, A. F., Kompaniyets, L., Summers, A. D., Danielson, M. L., Goodman, A. B., Chevinsky, J. R., Preston, L. E., Schieber, L. Z., Namulanda, G., Courtney, J., Strosnider, H. M., Boehmer, T. K., Mac Kenzie, W. R., Baggs, J. and Gundlapalli, A. V. (2021) Risk of Clinical Severity by Age and Race/Ethnicity Among Adults Hospitalized for COVID-19-United States, March-September 2020. Open Forum Infect Dis. 8, ofaa638
11 Nakatsuji, T., Kao, M. C., Fang, J. Y., Zouboulis, C. C., Zhang, L., Gallo, R. L. and Huang, C. M. (2009) Antimicrobial property of lauric acid against Propionibacterium acnes: its therapeutic potential for inflammatory acne vulgaris. J Invest Dermatol. 129, 2480-2488
12 Soliman, S., Faris, M. E., Ratemi, Z. and Halwani, R. (2020) Switching Host Metabolism as an Approach to Dampen SARS-CoV-2 Infection. Annals of nutrition & metabolism. 76, 297-303
13 Kohli, P. and Levy, B. D. (2009) Resolvins and protectins: mediating solutions to inflammation. British journal of pharmacology. 158, 960-971