Obesity has been known for years to be a major health problem. Rates of obesity have been steadily increasing all over the world. Many factors, including healthy eating habits and exercise, play important roles in controlling obesity. In our study, we compared the function of cells of the immune system called natural killer (NK) cells between healthy and obese groups of mice. We found that obese mice have lower numbers of NK cells and that NK cells from obese mice are less functional. Lower NK cell activity is related to a higher risk of infections and cancer in the obese group. This research could show a relationship between what we eat and our ability to defend ourselves against diseases like cancer.
What is Obesity?
Obesity is the term for being extremely overweight. Obese people have too much fat in their bodies. Scientists know that genes can contribute to a person’s likelihood of becoming obese, but other things, like lack of exercise and eating a high-fat diet, can also contribute to obesity. The number of obese people in the world is steadily increasing, and obesity is now treated as a disease. We know that obesity causes many health issues. For example, obesity can cause heart problems, because the excess weight makes the heart work too hard, so it gets tired sooner. When the heart gets too tired and weak, it might stop beating and pumping the blood, which can cause death. cardiac arrest or heart failure While we know obesity affects the heart, we do not know everything that it does to other parts of our body. Obese people have also been found to have a higher risk of cancer. Increased risk of cancer could be related to a decreased ability of the immune system to protect us from cancerous cells. Therefore, we decided to study cells of the immune system, to see if they are somehow different in healthy mice than in obese mice.
What is the Immune System?
The immune system is extremely important to keep us healthy. It helps defend against infections and diseases caused by bacteria and viruses, and it is also believed to help defend us against cancer. Since we depend on the immune system so much, it makes sense to keep it working at its best. The immune system needs several different kinds of cells to successfully defend our bodies. Figure 1 shows a list of the many kinds of immune cells the body uses to defend itself. All immune cells originate from cells called hematopoietic stem cells, which are found in the bone marrow. All of these immune cells are important, but our study focused on one type of cells, called lymphocytes.
You may ask, “What are lymphocytes?” Lymphocytes can be divided into three different types: T cells, B cells, and natural killer cells (Figure 1). Lymphocytes can remember what they attack. These memories allow the immune system to respond faster the next time they see the same threat. Faster responses mean we get sick less. Did you ever have the chickenpox? If so, you may have had lots of spots on your skin and felt sick for a long time. While you were sick, your immune system was fighting the chickenpox virus. During the fight, your lymphocytes attacked the virus and developed memory for it. After you got better, the memory lymphocytes could recognize the same virus if you came in contact with it again, and destroy it before spots could appear on your skin. Lymphocytes are good for attacking viruses, but not all of them are useful for attacking cancer cells. Natural killer (NK) cells are needed to fight cancer cells [1, 2, 3]. Since we were interested in why obese people are more susceptible to cancer, we decided to study the NK cells in both healthy and obese mice.
I Have Never Heard of NK Cells!
Not many people have heard of NK cells! NK cells were discovered in the early 1980’s for their role in killing cancer cells. NK cells only make up 5–10% of all your white blood cells. But even though there are so few of them, they are still very important. NK cells use two main molecular tools to protect your body: perforins and proteases. Perforins are used to punch holes in the outside walls of cancer cells. The holes allow proteases to invade the cancer cells. Once inside, the proteases attack and break down important cell parts that the cancer needs to spread and survive. If cancer is not able to spread and renew itself, it is much less dangerous. To successfully fight cancer cells, NK cells need to be healthy and fully functional (Figure 2).
Obese Mice Have Fewer, Less Active NK Cells
To see if diet could affect the number of NK cells, we fed mice with either a high fat-calorie diet (HFCD) or a control, healthy diet (CD). In 4–5 weeks, mice fed HFCD gained 2–3 times more weight compared to mice fed CD. Using flow cytometric analysis, we counted the number of NK cells in both obese HFCD mice and CD mice and found that there were fewer NK cells in obese mice (Figure 3A) [4, 5].
To see whether the NK cells from healthy and obese mice could kill cancer cells, we ran cytotoxicity assay in which NK cells are effector cells and tumor cells are targets. We found that NK cells from obese mice were less capable of killing cancer cells (Figure 3B). We think this means that, if the obese mice had cancer, the cancer could spread very easily because the NK cells of those mice are weaker and would not be able to destroy the cancer cells . Although this finding still needs to be confirmed in humans, the results obtained from mice suggest that obese people might also have a smaller number of NK cells and that those NK cells might be less functional than NK cells from non-obese people. This could help explain why obese people have a higher risk of getting cancer compared to healthy people.
Putting It All Together
The immune system is important. We use it every day for everything from fighting off infections that cause the sniffles up to more serious things, like protecting us from cancer. So, it is in our best interest to keep the immune system in great shape. When our bodies get out of shape and become obese, our natural killer cells may show signs of being out of shape, too. In obese mice, there are fewer NK cells and those cells do not do their job of defending mice very well. If these findings hold true in humans, this could make obese humans more vulnerable to cancer, perhaps making it easier for the cancer to spread from one organ to another. It is possible that simply eating a little less fat every day and keeping your body a little healthier may be enough to help your NK cells fight off your body’s enemies—even something as dangerous as cancer.
Obesity: ↑ The condition of being very fat or overweight.
Immune System: ↑ A system of the body that protects it from dangers, such as bacteria, viruses, etc.
Lymphocytes: ↑ A type of white blood cell involved in defending the body.
Natural Killer Cells: ↑ A type of white blood cell that attacks cancer cells or cells infected by a virus.
Perforin: ↑ A protein made by immune system cells that create holes in membranes.
Proteases: ↑ A type of protein that assists in breaking down other proteins.
Conflict of Interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
 ↑ Kaur, K., Nanut, M. P., Ko, M. W., Safaie, T., Kos, J., and Jewett, A. 2018. Natural killer cells target and differentiate cancer stem-like cells/undifferentiated tumors: strategies to optimize their growth and expansion for effective cancer immunotherapy. Curr. Opin. Immunol. 51:170–80. doi: 10.1016/j.coi.2018.03.022
 ↑ Kaur, K., Topchyan, P., Kozlowska, A. K., Ohanian, N., Chiang, J., Maung, P. O., et al. 2018. Super-charged NK cells inhibit growth and progression of stem-like/poorly differentiated oral tumors in vivo in humanized BLT mice; effect on tumor differentiation and response to chemotherapeutic drugs. Oncoimmunology 7:e1426518. doi: 10.1080/2162402X.2018.1426518
 ↑ Kaur, K., Cook, J., Park, S. H., Topchyan, P., Kozlowska, A., Ohanian, N., et al. 2017. Novel strategy to expand super-charged NK cells with significant potential to lyse and differentiate cancer stem cells: differences in NK expansion and function between healthy and cancer patients. Front. Immunol. 8:297. doi: 10.3389/fimmu.2017.00297
 ↑ Kaur, K., Chang, H. H., Topchyan, P., Cook, J. M., Barkhordarian, A., Eibl, G., et al. 2018. Deficiencies in natural killer cell numbers, expansion, and function at the pre-neoplastic stage of pancreatic cancer by KRAS mutation in the pancreas of obese mice. Front. Immunol. 9:1229. doi: 10.3389/fimmu.2018.01229
 ↑ Kaur, K., Chang, H. H., Cook, J., Eibl, G., and Jewett, A. 2017. Suppression of gingival NK cells in precancerous and cancerous stages of pancreatic cancer in KC and BLT-humanized mice. Front Immunol. 8:1606. doi: 10.3389/fimmu.2017.01606