The Manchurian Cell – The Relationship Between Fat and Cancer and Why Muscle Matters

In 2013, a scientific report on fat and cancer baffled scientists and physicians. A usual, the nightly news had a field day with the findings. A massive analysis of all available studies assessing weight status and survival revealed that being overweight or mildly obese was associated with longer survival in a group of individuals.1 Some evidence even suggested that overweight individuals may have been the healthiest with the lowest risk of cancer. Many, like myself read and watched this in disbelief. Have we been wrong all this time? Was a new French Paradox emerging?

Much like the French Paradox – which is no paradox at all, as many cultures that eat a high fat diet are healthier and live longer than the rest of the world – there was a simple explanation for this finding. Categorizing individuals by body mass index, or BMI, simply divides their body-weight by height squared. This tells us nothing about an individual’s muscle mass, fat mass, or metabolic function. In other words, someone can have a tiny amount of fat, but if they are blessed with substantial muscle, can expect to be labeled in the obese category just the same as someone with minimal muscle mass and a whole lot of fat. While the same on paper, the muscular individual could expect significantly healthier metabolic function, lower circulating blood sugar, insulin, and inflammation, and a much easier time lowering blood sugar after a meal, as their healthy physique leaves them more insulin sensitive. As a result, their pancreas spends less time under stress throughout the day as it does not have to over-perform to balance blood sugar.

In reality, the muscular individual is generally expected to be healthier than someone with a lower BMI and equivalent amount of body fat, as our muscles are more than just push and pull robots embedded around our joints and bones. Muscles make up, in reality, a potent organ that secretes chemicals and hormones that help regulate our metabolism and impact our health. LINK When summoned to lift heavy weights and propel us around the curves of the local track as we run sprints on Saturday mornings, these muscles do more than mobilize. They secrete anti-inflammatory hormones to help lower our risk of cancer, burn sugar to help our pancreas perform its best, and lower the amount of insulin our body needs to keep its sugar levels in check. These changes leave our body more metabolically healthy, more capable of fixing the daily wear and tear on our cells, and with an immune system that is more able to fight disease, infection, and cancer.

This guy’s abs have nothing to do with this article, but I have been told to put more pictures in my articles, so here you go!

Fat, on the other hand, is more than a gooey substance that surrounds our organs and muscles, providing them a blanket of heat and a fuel source between meals. Fat, like muscle, is an endocrine organ that secretes hormones and messages to the rest of the body as a feedback mechanism to let it know how things are going in adipose tissue land. Fat also directly impacts the cells surrounding it, along with the rest of the body.

And this is where the trouble begins…

The Manchurian Cell – The Relationship Between Fat and Cancer

It is as if an innate biological switch is permanently flipped into the “on” position. The cell begins to grow, and then continues to grow. And grow. Throughout the process, it sprouts new blood vessels to provide inroads for additional fuel and nutrition in preparation for even more growth. Hormones, or cellular command messengers, are released, demanding that local cells secrete even more hormones, igniting a chain reaction that attracts vascular cells to blood vessel seed-like agents, eventually sprouting vascular extensions that creep along like the roots of a tree. These roots then extract further fuel and nutrients for the ever-growing cells.

A chain reaction is ignited; the cells eventually secrete more and more hormones until organs located in distant locations are affected. The cells begin to interfere with normal cellular function and all hell breaks loose. The insulin circuit becomes rewired, making it less effective at lowering blood sugar. The decrease in insulin sensitivity eventually leads to a rise in blood sugar, sounding several alarms as the body attempts to fight this dangerous state of hyperglycemia. Stress hormones and inflammation are released, and accumulate throughout the body as it begins to experience metabolic mayhem. This cellular Manchurian candidate acts swiftly to take control of a once normally functioning body. The pancreas is stressed into overdrive as it is required to pick up the slack and produce more insulin than it can handle. The increase in insulin pulls the excess sugar out of the blood and into the expanding cell, supporting further growth and replication, creating a dangerous feedback loop that spirals out of control. The body feels as though it is starving as all the nutrients begin to fill this cellular pandora.

As mayhem is in clear view, the cells are consuming so much of the hosts food that she continually feels hungry, eating more and more. Yet, the cells continue to engorge themselves with no attempt of stopping. She feels as though she is dying of hunger, yet these cells continue to grow massively as she eats more and more food. These cells eventually cause so much disruption that she loses significant muscles mass, and her metabolism begins to fail as her blood sugar rises higher and higher, creating more and more free radical and oxidative damage in her cells, further damaging her normal DNA. This feedback mechanism calls on the pancreas to secrete even more insulin. Eventually, counter to any logic, the havoc wreaked from these cells eventually takes the life of their master.

These fickle cells appear to have turned on their master. But what made them this way?

By the time this cancerous chain of events becomes a systemic problem it is difficult, if not impossible to treat. Chemotherapy, radiation, surgery? Not this cancer, because this cancer is no cancer at all. This cancer is normal fat tissue that has been sent countless commands to stop behaving normally, go rogue, and behave like a cancer. The signal was so consistent that, eventually, it threw in the towel, followed command, and became a Manchurian candidate. The massive number of checks and balances set up to avoid the excessive growth of fat tissue – adipose cells – were finally overwhelmed leaving it no other recourse.

Fat and Cancer are Remarkably Similar

The description above only approaches some of the issues with excess fatty tissue, known as adipose tissue. Fat tissue in our body contains a diversity of unique vessels, cells, and structural components which, together, comprise what is now known as the adipose tissue microenvironment. This environment produces inflammation and sends varying signals to the rest of the body, interfering with immunity, metabolism, and the body’s ability to fight cancer.

As I described this terrible process, you likely contemplated just how terrible cancer can be, and just how much havoc it causes throughout the human body. You would, of course, be wrong. These necessary fatty cells within our body, when turned loose, can unexpectedly closely resemble the deadly disease known as cancer, yet few have ever considered the analogy.

I have come to view fat as, much like cancer, a normal part of our body that goes rogue for some reason. The connections between the description of fat gone awry and cancer, as described above, comes full circle from the multiple studies that reveal an increased risk of cancer in those individuals with excess adipose tissue.2 As obesity not only continues to rise, but also presents at an earlier age, perhaps most frightening is the finding that excess bodyfat in children and adolescents increases the risk of cancer later in life.3

Perhaps sealing this connection, is the sinister ability of fat cells to provide nutrients to rapidly growing cancer cells, feeding their expansion and, ultimately, their own demise.4,5 Furthermore, fat tissue in close proximity cancer cells appears to promote blood vessel formation in those cancer cells, one of the main hallmarks of cancer.6 When fat is not acting like cancer, it is acting as its accomplice, helping cancer to survive, grow, and spread.

The Good News – Fat and Cancer

Whereas many of the environmental and internal genetic risks of cancer are difficult to impact, we do have the power to affect our levels of fatty tissue. Furthermore, we have an antidote to the metabolic mischief fat imparts on our body: muscle.

Muscle is an antidote to this fatty cancer. You read that right. Muscle is that antonym to fat, and having excess amounts will help prime our metabolism to lower inflammation and blood sugar, and help reduce potentially cancerous free radical damage. Additionally, exercising those muscles by lifting heavy things forces them to secrete beneficial chemicals that improve our body’s ability to counter harmful inflammation.7

While the similarities between cancer and fat are frightening, the differences are encouraging, as they empower us and provide us with an Achilles’ heel where we can strike to improve our overall health and reduce our risk of cancer. Cancer, once established, may leave us with a limited number of viable options to treat it. Excess fat, on the other hand, may be difficult to treat, but we are completely able to rid our body of it while increasing our muscle mass through a healthy lifestyle. Higher amounts of muscle and muscular strength are even associated with lower risks of cancer and better outcomes in those who are battling cancer.8,9

The benefits of more muscle include:

  • Improved insulin sensitivity (less insulin needed to remove sugar from our blood)
  • More sugar extracted from our blood by skeletal muscle during exercise and used for energy
  • Less cancer-promoting sugar and insulin within our system
  • A decrease in the levels of hormones that, over a prolonged period, can lead to cancer. For instance, resistance training increases IGFBP-3, which binds to insulin-like growth factor (IGF), decreasing its ability to promote cancer (growth factors are normal within the human body, but too much can lead to excessive cellular growth, including cancer growth)10
  • Decreased inflammation (which serves as a fertilizer for cancer)
  • Increased antioxidant defense, which helps fight potential cancer-causing free-radicals
  • Less inflammation-producing bodyfat

Muscles help us edge out the issues with excess fat:

  • Adipose-derived Tumor Necrosis Factor (TNF) is inflammatory, while muscle-derived IL-6 is anti-inflammatory.
  • Muscle-derived IL-6 signals to our body to break down lipids and burn fat.11
  • Adipose-derived TNF causes insulin resistance and impairs glucose uptake by our cells (both leading to increased blood sugar).12
  • While serious and often fatal events like septic shock cause a sudden release of TNF, excess adipose tissue chronically releases small amounts of harmful TNF.
  • Muscle-derived IL-6 helps regulate AMPK (while muscle contraction directly activates AMPK), promoting the breakdown of fat and cholesterol, stimulating our mitochondria, and potentially reducing the risk of cancer.13

fat and cancer
If you are going to the gym and hanging out on the treadmill or stair-climber, you are selling yourself short. More intense exercise may be a little harder than chugging away, but will pay dividends.

For more information on how muscles help us edge out the issues of fat, check out the article Muscles Fight Cancer – The Science Behind Outmuscling Cancer. I hope this article has provided some food for thought and insight into the metabolic issues with having too much fat. If you are concerned and looking for somewhere to go to try to lose weight and reduce your amount of excess fatty tissue and risk of cancer, check out the guide I made for my patients A Basic Lifestyle Guide after Breast Cancer Treatment LINK. Otherwise, follow an Intentional Lifestyle, lift heavy weights periodically (regardless of your age, sex or anything else), fast periodically, eat vegetables that promote a healthy immune system, and stick to real nutrient-dense and vitamin-rich foods. If you are looking for an enjoyable way to keep the fat off and stay healthy, The Mediterranean Ketogenic Lifestyle has worked well for me and many of my friends, family members, and patients.

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Fat and Cancer References:

    1. Flegal KM, Kit BK, Orpana H, Graubard BI. Association of All-Cause Mortality With Overweight and Obesity Using Standard Body Mass Index Categories. JAMA. 2013;309(1):71. doi:10.1001/jama.2012.113905
    2. Calle EE, Kaaks R. Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat Rev Cancer. 2004;4(8):579-591. doi:10.1038/nrc1408
    3. Berger NA. Young Adult Cancer: Influence of the Obesity Pandemic. Obesity. 2018;26(4):641-650. doi:10.1002/oby.22137
    4. Nieman KM, Kenny HA, Penicka C V, et al. Adipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth. Nat Med. 2011;17(11):1498-1503. doi:10.1038/nm.2492
    5. Meyer KA, Neeley CK, Baker NA, et al. Adipocytes promote pancreatic cancer cell proliferation via glutamine transfer. Biochem Biophys Reports. 2016;7:144-149. doi:10.1016/j.bbrep.2016.06.004
    6. Arendt LM, McCready J, Keller PJ, et al. Obesity Promotes Breast Cancer by CCL2-Mediated Macrophage Recruitment and Angiogenesis. Cancer Res. 2013;73(19):6080-6093. doi:10.1158/0008-5472.CAN-13-0926
    7. Pedersen BK. Muscles and their myokines. J Exp Biol. 2011;214(Pt 2):337-346. doi:10.1242/jeb.048074
    8. Ruiz JR, Sui X, Lobelo F, et al. Muscular strength and adiposity as predictors of adulthood cancer mortality in men. Cancer Epidemiol Biomarkers Prev. 2009;18(5):1468-1476. doi:10.1158/1055-9965.EPI-08-1075
    9. Caan BJ, Cespedes Feliciano EM, Prado CM, et al. Association of Muscle and Adiposity Measured by Computed Tomography With Survival in Patients With Nonmetastatic Breast Cancer. JAMA Oncol. 2018;4(6):798. doi:10.1001/jamaoncol.2018.0137
    10. Izquierdo M, Ibañez J, González-Badillo JJ, et al. Differential effects of strength training leading to failure versus not to failure on hormonal responses, strength, and muscle power gains. J Appl Physiol. 2006;100(5).
    11. Hall G van, Steensberg A, Sacchetti M, et al. Interleukin-6 Stimulates Lipolysis and Fat Oxidation in Humans. J Clin Endocrinol Metab. July 2013.
    12. Plomgaard P, Bouzakri K, Krogh-Madsen R, Mittendorfer B, Zierath JR, Pedersen BK. Tumor necrosis factor-alpha induces skeletal muscle insulin resistance in healthy human subjects via inhibition of Akt substrate 160 phosphorylation. Diabetes. 2005;54(10):2939-2945.
    13. Shackelford DB, Shaw RJ. The LKB1-AMPK pathway: metabolism and growth control in tumour suppression. Nat Rev Cancer. 2009;9(8):563-575. doi:nrc2676 [pii]10.1038/nrc2676

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