Ok people, this book is awesome! After this excerpt you may be a little confused about some of the terms. This is one reason why I HIGHLY recommend this book. It takes the most intricate mechanisms of the digestion processes and illustrates these mechanisms in a way the everyday person can grasp! It's your body people! You should want to know how it works!! Enjoy!
Overfed State
Big picture: Overfeeding is a problem. I know, shocking, right? Well, here's the thing: our physiology is actually wired to exist at a caloric excess. Goofy dietitians and some "nutritional scientists" will tell you we need to maintain a caloric "balance" to remain slim and healthy. This is baloney. Figuring out a caloric balance is virtually impossible if it's left up to "us." Metabolic studies have shown an enormous variance between people and how they handle calories. One person can overeat several hundred calories every day for years and never gain a kilo. Other people seem to gain wight by looking at food. What gives? What's the difference? Hormones and the signals associated with hormones.
It should not comae as a surprise that our bodies have complex sensors that tell us not only if our blood glucose is high or low, but also how much total energy we have in storage. Leptin, which tells the brain we are "full," is not only released in response to food, but it is also released from our body fat. This should make sense on a mechanistic level: A relatively large amount of fat will release a relatively large amount of leptin, which sends a signal "I'm full, no need for more food." Conversely, if we are getting very lean and our energy reserves become low, our leptin signal will be low and we experience hunger.
What does all this have to do with overfeeding, health, and disease? As I was saying before, we are wired to live at a caloric excess. Certain foods affect our sense of satiety and the ultimate fate of our food in very different ways. Think about the difference between the satiety signals produced by protein (very satiating) and carbohydrate (in many people low satiety actually acts as an appetite stimulant). what if we are overfed, but for some reason our brain no longer "hears" the "I'm full" signal from the leptin? What if, despite significant overfeeding, we still think we are hungry? That situation creates one hell of a problem, as you will see.
Protein: In the initial stages of protein overfeeding things run as you might expect: Some amino acids are used for structural repair, but any amino acids beyond this are converted to glucose via gluconeogenesis, or burned directly as a fuel. Protein can add to overall caloric excess, but as a stand-alone item, it is virtually impossible to overeat protein due to the potent satiety signal sent to the brain. Part of the reason for this signal is due to a maximal ability of the liver to process protein set at 30-35 percent of total calories. Protein consumption beyond this point for extended periods of time results in a condition called "rabbit starvation," so named by early pioneers of the American West who would succumb to a disease characterized by muscle wasting, lethargy, diarrhea, and eventually death if one relied too heavily on lean game animals such as rabbits. We will take advantage of the satiating effects of protein to help us remain lean and strong, while rounding out our meals with nutritious fruits, vegetables, and good fats to avoid potential of too much protein.
Carbs: This next piece is going to be longish but wickedly important. Drink some espresso, stick your head out the window, and yell "I've go to get my head back in the game!"
So, you are now familiar with the fate of glucose (and fructose) as it enters the body and is stored as glycogen in either the muscles or liver. What we have not considered is what happens if liver glycogen is completely full but there is still excess free glucose in circulation (high blood glucose levels). Once liver liver glycogen is full, excess carbohydrates are converted to fat in the form of a short-chain saturated fat called palmitic acid. This palmitic acid (PA) is stitched to a glycerol molecule and packaged with proteins and cholesterol, and the resultant molecule is called a VLDL (very low-density lipoprotein). this PA-rich VLDL molecule is released from the liver and heads out to the body so the fat may be used as a fuel or get stored on our fannies.
DEFCON 1
Although VLDL's move all about the body, one location they interact with is the brain. PA has a very potent effect on our metabolism and our hormonal environment in that it decreases our sensitivity to leptin. When the brain, specifically the hypothalamus (the area of the brain responsible for energy regulation), becomes leptin resistant, the satiety signal that is normally sensed from ingested food is lost. We remain hungry, despite elevated blood glucose levels, and continue to eat beyond our needs. We develop a "sweet tooth" because we cannot sense the normal signal sent by leptin that we are "full." Keep in mind, this Palmitic acid (PA) that causes the leptin resistance in the brain leads to our inability to feel full, and is made from excess dietary carbohydrate.
DEFCON 2
This process happens in waves. Like the ocean eroding a sand castle, our insulin sensitivity is degraded and we lose the ability to respond properly to the signal. The liver becomes insulin resistant and blood glucose levels drive higher and higher. Insulin sensitivity in our muscle tissue is lost when they can physically store no more glycogen. the gene expression for the GLUT4 transport molecule is down-regulated because the muscles are literally drowning in glucose. this drives blood sugar higher, which drives insulin higher. Eventually, even the fat cells become resistant to insulin. Things are about to get bad rather quickly.
DEFCON 3
Once systemic, full-body, insulin resistance occurs, inhibitory systems in the liver are overwhelmed and blood glucose is converted into fats and VLDLs at such a high rate that fat cannot escape into circulation, and it begins to accumulate in the liver. This is the beginning of non alcoholic fatty liver disease. The wheels are seriously falling off the wagon by this point, as is evidenced by the next malfunction that occurs: Despite the fact the liver (in fact, the whole body) is swimming in glucose, the liver is insulin resistant and certain cells perceive the "lack of insulin" as low blood sugar. Your body does not like low blood sugar. Low blood sugar can kill you, so your body brings the stress hormone cortisol to the "rescue," and it's like throwing gasoline on a fire.
CHINA SYNDROME: FULL SYSTEM MELTDOWN
Cortisol is released to combat the perceived low blood glucose levels with gluconeogenesis. Yes, despite high levels of blood glucose from excess carbohydrate, the body now makes more glucose by cannibalizing its own tissues. In this case, muscles and organs are "burned" to make more glucose. Keep in mind, the muscles are a primary site of dealing with elevated blood glucose in the first place! So, not only is the situation made worse by adding more glucose to the blood from gluconeogenesis, we have less muscle with which to dispose of all that glucose.
This is why type 2 diabetes and insulin resistance is effectively a wasting disease of the muscles, all the while the fat cells experience record growth. Because of the high insulin, blood sugar, and triglycerides, a significant portion of the fat is stored in the abdominal region. this is the telltale sign of insulin resistance: fat stored at the waistline, creating the very sexy "Apple Shape." We have now set the stage for chronically elevated insulin levels and all the fun that brings: Increased rates of cancer, accelerated aging, and neurodegenerative diseases such as Parkinson's and Alzheimer's, obesity and, ultimately, type 2 diabetes, which is characterized by insulin resistance and chronically elevated blood glucose levels.
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