Obesity

Jasmin Reyes

Undergraduate from Lamar University

However, if adipose cells accumulate, they begin releasing toxins which incite inflammation, which can cause cancer if left unchecked. [4] Adipose cells also signal nearby cells to make more cells faster, which increases the chance of mutations and faulty signaling. [5] Some may argue that poor diets create an acidic environment for microbials to thrive and cause cancer. Microbials can cause certain types of cancer. While consumption of junk food can make the body’s internal environment more acidic, most microbials prefer neutral environments and are not the sole cause of cancer. [6, 7, 8] In summary, obesity can be treated through a controlled diet, medication, and surgeries, depending on what the individual and their health care team deems best. [3] Treating obesity can be a strong early defense against cancer.

References

1. Weinstein LC, Stefancic A, Cunningham AT, Hurley KE, Cabassa LJ, Wender RC. Cancer screening, prevention, and treatment in people with mental illness. CA Cancer J Clin. 2016;66(2):134-151. doi:10.3322/caac.21334
2. Zhu Y, Sidell MA, Arterburn D, et al. Racial/Ethnic Disparities in the Prevalence of Diabetes and Prediabetes by BMI: Patient Outcomes Research To Advance Learning (PORTAL) Multisite Cohort of Adults in the U.S. Diabetes Care. 2019;42(12):2211-2219. doi:10.2337/dc19-0532
3. Panuganti KK, Nguyen M, Kshirsagar RK. Obesity. [Updated 2020 Jun 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459357/
4. Kompella P, Vasquez KM. Obesity and cancer: A mechanistic overview of metabolic changes in obesity that impact genetic instability. Mol Carcinog. 2019;58(9):1531-1550. doi:10.1002/mc.23048
5. Haider N, Larose L. Harnessing adipogenesis to prevent obesity. Adipocyte. 2019;8(1):98-104. doi:10.1080/21623945.2019.1583037
6. Gupta P, Shah D, Kumar P, et al. Indian Academy of Pediatrics Guidelines on the Fast and Junk Foods, Sugar Sweetened Beverages, Fruit Juices, and Energy Drinks. Indian Pediatr. 2019;56(10):849-863.
7. Korbecki J, Bajdak-Rusinek K. The effect of palmitic acid on inflammatory response in macrophages: an overview of molecular mechanisms. Inflamm Res. 2019;68(11):915-932. doi:10.1007/s00011-019-01273-5
8. Microbiology. Lumen. https://courses.lumenlearning.com/microbiology/chapter/the-effects-of-ph-on-microbial-growth/. Accessed August 4, 2020.

Full Article

In 2002 the International Agency for Research on Cancer (IARC) concluded that there is adequate evidence of association between obesity and several cancers affecting various organs, including: colon, postmenopausal breast, endometrium, kidney, and esophagus. [1, 2] Additional information was then published which indicated a link between obesity and additional cancers including hepatic, pancreatic, non-Hodgkin’s lymphoma, and myeloma. [3] Obesity has been shown to cause issues with cell metabolism, inflammation, and cell division in adipose tissue, which in turn leads to cancer.

Most scientists and health professionals define an obese person as someone whose body mass index (BMI), or ratio of weight to height (weight/height), is 30 or higher. [3] Some individuals who have a normal BMI, less than 25 kg/m², have been shown to acquire unusual stores of fat which affect metabolism similar to those who are determined to be obese based on BMI. In this sense a person is considered to be metabolically obese, or to have a metabolically unhealthy normal weight (MUNW). [4, 5] The unusual fatty tissue in nonobese individuals tends to cause many of the same conditions in the non-obese patients as it would in the obese patients such as Type 2 Diabetes Mellitus, high blood pressure and high cholesterol. [4] It has been found that addressing obesity symptoms and obesity related disease in individuals who have an MUNW is often harder with an increased number of adverse effects and higher mortality rate. [4] Obesity is commonly caused by an imbalance between calories consumed and calories used in which a person does not burn as many calories as they have eaten. [6] Even in patients with a normal weight who are metabolically obese, where more testing is needed to address the cause of their abnormal metabolism, moderately reducing their weight through diet has shown to improve symptoms of their metabolic condition. [5] The imbalance of nutrient intake and expenditure in patients with obesity and obese metabolisms causes changes in the way cells store and use energy.

The process of cellular metabolism (storage and use of energy and nutrients) can be compared to eating food at a restaurant. When the meal first arrives at the table and you are hungry, you can gobble up the food in front of you quickly. Now, say you ordered more, and you got full halfway through your second course. Most people would have to ask for a to-go container so they can save that food to eat later. In your body, different nutrients from the foods you eat feed your cells so they can perform their normal functions, but they do not always utilize all of the nutrients you consume right away. When there is an overabundance of nutrients, cells need to package them away for later, except instead of putting the leftovers in Tupperware and to-go boxes, they bind excess nutrients with other molecules until they are needed. When there are far too many excess nutrients, molecules that should not be used for holding those excess nutrients begin binding with the nutrients to hold them for later. [1]

One molecule that may be affected by excess nutrients is DNA. When parts of the DNA bind with excess nutrients, they are no longer able to be used as part of the DNA, leaving gaps in the sequence and creating mutations. Some of the affected parts of the DNA may be growth regulating sections which, when damaged, lose their ability to control cellular growth and division resulting in cancer.

Damage to DNA is not uncommon, it can happen from all manner of things, even during the replication process where cells are supposed to copy themselves exactly to make new cells. Since DNA damage can happen often, cells have a sort of built in fail safe. It comes in the form of proteins which target and fix these errors. Sometimes excess nutrients bind with these proteins as well. When nutrients bind with these proteins, it leaves the proteins unable to fix damage in the DNA. This makes cells slow to repair damage to their DNA and increases the opportunity for further mutations. [1] These mutations can then be replicated in future cells, who will be subjected to the same stressors as the original cell to add to its already unstable state, leading to a conglomeration of changes in the DNA, which can result in the uncontrolled growth and division seen in cancer.

The functions used for storing excess nutrients in the body also result in the release of toxins that signal the inflammatory response. [1] In order to explain how obesity can cause inflammation, we will continue with our previous analogy of cells storing nutrients the way we store food. After you pack your food away into Tupperware containers, it cannot be left on the counter. It usually needs to be put in the fridge. Similarly, the nutrients that have been bound to other molecules for safe keeping cannot float around in your cells. They take up too much space. Instead the body has specialized cells called adipose, or fat storing, cells whose main job is to store excess nutrients for later, just like your fridge stores your leftovers. While storing leftover food in the fridge can save money for a few days, storing too much food and not using it leaves you with a stinky fridge full of spoiled food. This is similar to how stored nutrients affect the body. A few extra nutrients stored in your adipose tissue, tissue made of fat storing cells, are useful for a short period later when your body might need a little extra fuel and there is not any food readily available. However, in the case of someone who is obese, they regularly eat more food than their body uses leading to an excessive amount of storage and a buildup of adipose tissue. When those extra nutrients are left to accumulate for too long, they can begin to release toxins which signal the inflammatory response. If left untreated, the excess adipose tissue can increase inflammation as it continues to create toxins and can ultimately lead to chronic inflammation, which is another factor that can lead to cancer. [1]

Obese individuals generally need much more storage space for their excess nutrients than a person with a normal weight. The extra storage space needed in obese individuals results in signaling that leads to the creation of more adipose cells which is achieved in two ways. One way is to prompt a type of cell called stem cells to divide and differentiate more frequently, and often prematurely, into adipose tissue, and another is to prompt existing adipose cells to replicate more frequently. [7]

Stem cells are like children in the cell world. They do not have any special jobs yet, but they have the potential to grow up and do all kinds of different specialized jobs. At some point these cells, like children, have to grow up and take on a certain job or function. This point is called differentiation. Once cells differentiate, they are considered specialized and can no longer switch jobs, but they can continue to make more specialized cells. Stem cells are often signaled by the body as to when they need to divide and create more stem cells or differentiate into whatever cells are needed. There are stem cells in and around the adipose tissue which continue to replenish the supply of adipose cells when they are needed. In obese patients, these stem cells are signaled by their surrounding cells to differentiate earlier and more frequently than they would be prompted to do in non-obese individuals. [7] This accelerated division and differentiation can lead to cancer causing mutations.

The second way the body makes more adipose cells for excess nutrient and fat storage is by signaling already existing adipose cells to divide more frequently. When a cell divides, it essentially makes two copies of itself. When cells are put under stress to divide more rapidly, it leaves room for errors to occur during the copying process. This can lead to faulty signaling in cells and increase the chance and number of mutations. These processes, mixed with the stresses that obesity puts on the cell, DNA and proteins, increases the chances of cancer incidence.[7]

Some theories about what causes cancer take the information about how cells alter their metabolism of nutrients in obese individuals and how a poor diet plays into obesity and cancer in a different direction. According to the microbial theory, a theory which states that all cancers are caused by microbial invasions, a poor diet creates an acidic environment which is optimal for microbial survival. While scientific evidence suggests that cancer is caused by mutations in tumor suppressing genes there are some truths to this theory. It has been shown that infection by microbes can cause cancer, but that is because the microbes alter cells’ DNA, through various methods which we discuss on the “How Infections Cause Cancer” article on this site. These microbial invasions are by no means the sole cause of cancer-causing mutations and they are not the largest contributing factor to these types of mutations, but they do account for some cancers. As for diets high in junk food creating an optimum environment for microbials by making the blood by lowering its pH, otherwise known as increasing its acidity, scientific evidence does diets that include large quantities of highly processed foods and junk foods are associated with higher BMIs and metabolic changes seen in obese individuals. [8] It has also been found that there are higher concentrations of acid in the blood of individuals with obesity.[9] This acidity then incites the inflammatory response by the immune system. [9] Most microbials cannot survive in an environment that is outside of a certain acidity range, typically around a pH of 7, meaning that if the acidity caused by obesity was enough to change the pH of the blood, it would most likely not be helpful for microbials. [10] Inflammation also generally works against microbials as it is part of the body’s immune defense against foreign invaders.

Understanding obesity can help explain ways in which preventative measures can be implemented. Since obesity is primarily caused by an imbalance between the ratio of nutrients in which a person consumes more nutrients than they use, treatment methods include ways to return that balance. Typically, patients are put on restrictive diets to decrease caloric intake by reducing the amount of carbs or fat they eat. [6] Other treatment options for obesity include behavioral interventions, medications, and surgeries. It is best to consult a doctor to assess what are the best weight loss options and plans for an individual. [6] Taking the appropriate measures to maintain a healthy body weight can be a strong defense and assist in the body’s overall health and a key component to cancer prevention.

References

1. Kompella P, Vasquez KM. Obesity and cancer: A mechanistic overview of metabolic changes in obesity that impact genetic instability. Mol Carcinog. 2019;58(9):1531-1550. doi:10.1002/mc.23048
2. Weinstein LC, Stefancic A, Cunningham AT, Hurley KE, Cabassa LJ, Wender RC. Cancer screening, prevention, and treatment in people with mental illness. CA Cancer J Clin. 2016;66(2):134-151. doi:10.3322/caac.21334
3. Zhu Y, Sidell MA, Arterburn D, et al. Racial/Ethnic Disparities in the Prevalence of Diabetes and Prediabetes by BMI: Patient Outcomes Research To Advance Learning (PORTAL) Multisite Cohort of Adults in the U.S. Diabetes Care. 2019;42(12):2211-2219. doi:10.2337/dc19-0532
4. Olaogun I, Farag M, Hamid P. The Pathophysiology of Type 2 Diabetes Mellitus in Non-obese Individuals: An Overview of the Current Understanding. Cureus. 2020;12(4):e7614. Published 2020 Apr 10. doi:10.7759/cureus.7614
5. Klitgaard, H.B., Kilbak, J.H., Nozawa, E.A. et al. Physiological and Lifestyle Traits of Metabolic Dysfunction in the Absence of Obesity. Curr Diab Rep 20, 17 (2020). https://doi.org/10.1007/s11892-020-01302-2
6. Panuganti KK, Nguyen M, Kshirsagar RK. Obesity. [Updated 2020 Jun 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459357/
7. Haider N, Larose L. Harnessing adipogenesis to prevent obesity. Adipocyte. 2019;8(1):98-104. doi:10.1080/21623945.2019.1583037
8. Gupta P, Shah D, Kumar P, et al. Indian Academy of Pediatrics Guidelines on the Fast and Junk Foods, Sugar Sweetened Beverages, Fruit Juices, and Energy Drinks. Indian Pediatr. 2019;56(10):849-863.
9. Korbecki J, Bajdak-Rusinek K. The effect of palmitic acid on inflammatory response in macrophages: an overview of molecular mechanisms. Inflamm Res. 2019;68(11):915-932. doi:10.1007/s00011-019-01273-5
10. Microbiology. Lumen. https://courses.lumenlearning.com/microbiology/chapter/the-effects-of-ph-on-microbial-growth/. Accessed August 4, 2020.