THE PERFECTLY KNOWN CAUSES OF OBESITY: Ketones, Glucagon, Muscle, and Fat

In this series, we will look at the basics of metabolism and discuss the very well-known science around obesity. Many of the diseases that bedevil humanity flow from obesity, including cancer and Type 2 diabetes, and so understanding metabolism and the causes of obesity is ground zero in the fight for a long life and good health.

The role of insulin is well understood in the body as is the effect of insulin as it rises and falls. When a person consumes carbohydrates, the beta cells in the pancreas release insulin and it escorts the resultant glucose coming out of the digestive system into cells around the body, including the liver and muscles. If there is excess, the body does not excrete it out; it is the assumption of the body that energy is precious and excess energy should be stored for future use. Insulin escorts this glucose into the adipose tissues. The adipose cells exist to store the extra energy as fat.

As the levels of glucose in circulation falls, insulin falls, and the pancreas secrets another hormone called glucagon. Glucagon is the opposite of insulin in that rising levels of glucose stimulate insulin and falling glucose causes the stimulation of glucagon. Glucagon causes the liver to engage in glycogenolysis which converts glycogen in the liver to glucose which is released into the blood stream (which triggers more insulin).

These two hormones, insulin and glucagon, and storage mediums in the liver, muscles, and adipose tissue, are what allows the body to stay in energy balance even when the supply of incoming energy in the form of food is sporadic. The body can stay steady even with unsteady inputs. The resulting homeostasis is all part of the physical genius of the body and far supersedes the simplistic notion of ‘calories in calories out.’

As previously noted, the world of things that humans can eat is vast, but it consists of only three ‘macros’ which are carbohydrates, proteins, and fats. The balancing act described above manages the energy balance when glucose, derived from consuming carbohydrates, is the primary fuel source. But, what if the glucose is fully depleted or not much was ever generated because the person didn’t eat many carbohydrates to begin with?

 When glucose isn’t available, the body begins to use the fat stores for fuel. This process involves ketones. ‘Ketone bodies,’ as they are called, are produced in the liver and they are the fuel source the body goes to after the glucose stores have been fully exhausted. Ketones are produced via a process called gluconeogenesis, which is a process the body uses to produce glucose from non-carbohydrate sources.

It is important to note that the glucose surge from incoming carbohydrates stimulates insulin, but the glycogen back-up system begins the process of converting the body over to fat metabolism. When this happens, and the liver is putting out ketone bodies, which, through a complex chemical process, begins to convert the body to fat burning. The process puts the body in a state of ‘ketosis’ which is where ‘ketogenic’ diets come from. Being in ketosis takes a while since the glucose and glucagon must to burn off, but after a 24 hour fast, or heavy exercise, or carbohydrate restriction, ketosis begins and the fat tissue is metabolized. If there are very few carbohydrates coming in, and the body doesn’t have glucose to burn, and ketones are secreted, and fat burning begins.

But note that NONE of this, the entire process of getting to the fat burning stage, is going to happen if insulin is present which is set in motion by carbohydrates. Insulin escorts excess energy in to the adipose tissue and there is stays, in the form of triglycerides, until something, like ketone bodies, causes it to be used.

There are a couple of other things to note regarding the various tissues of the body. The first is the muscles. It has long been known that muscle tissue forms a sort of ‘glucose sink’ that takes up glucose from the blood after eating. PubMed describes the phenomenon this way:

As the single largest organ in the body, the skeletal muscle is the major site of insulin-stimulated glucose uptake in the postprandial state. Skeletal muscles provide the physiological foundation for physical activities and fitness. Reduced muscle mass and strength is commonly associated with many chronic diseases, including obesity and insulin resistance.

‘Postprandial’ means after a meal.

People that are more heavily muscled have a place for the glucose to go that is not stored adipose tissue, or fat. More heavily muscled people have this ‘sink’ available and so they have an easier time dealing with the carbohydrate load. Less muscle means the extra glucose must be moved in to the fat tissue.  

Why, other than just the negative aesthetics of being fat, would one want enter ketosis and get the adipose tissue to release the stored energy? The reason is because excess fat is implicated in all the big killers. Here is but one of many description of the pathology of the tissue that only ketone bodies can eliminate:

Far from being hormonally inert, adipose tissue has, in recent years, been recognized as a major endocrine organ, as it produces hormones such as estrogen, resistin, and cytokines. In obesity, adipose tissue is also implicated in the chronic release of pro-inflammatory markers, which are responsible for the development of metabolic syndrome, a constellation of diseases including, but not limited to, type 2 diabetes, cardiovascular disease and atherosclerosis.

The message is clear: poorly muscled people who consume highly refined carbohydrates store the resultant glucose as fat. The insulin/glucagon cycle keeps them in homeostasis, but all the stored glucose in the fat tissues is leading them to an early grave.