Glyceroneogenesis, and Other Reasons for Fat Storage on Zero Carb

This week I have an extra set of responsibilities in real life and have had a hard time finding time for a new blog post. Fortunately I recently learned of an excellent article by LynMarie Daye, Is the Fable of Unfettered Fat Burning Derailing Your Low Carb Diet?

The author explains in clear and well-referenced terms how the body is able to store fat in the relative absence of insulin. As she says, only type-1 diabetics have a total absence of insulin, and it is true that they cannot store fat. However, the rest of us have a low baseline level of insulin at all times, and in that situation, Acylation Stimulating Protein is able to promote fat storage even when blood insulin levels remain low.

It is also true that fat storage requires the presence glycerol 3-phosphate to form the backbone of the triglyceride molecule. However, simply refraining from eating carbs is not sufficient to stop the synthesis of glycerol 3-phosphate. Even in a state of prolonged fasting, the body is able to use its own muscle protein to synthesize glycerol 3-phosphate. This metabolic pathway is called glyceroneogenesis, and it is illustrated in the figure above.

If you have ever wondered how it is possible to eat no carbs whatsoever and still gain weight, LynMarie Daye provides a thorough treatment of the issue. I highly recommend her article.

Ghrelin, the Hunger Hormone

A hormone is a chemical that is produced in one part of the body, is released into the blood, and is able to regulate activities in other parts of the body. One example would be insulin, which is produced in the pancreas, but affects the function of tissues throughout the body, including muscles, brain and liver.

Insulin is important for food storage and satiety. Another hormone that plays a role in energy homeostasis is ghrelin, a 28-amino acid peptide discovered in 1999. Its name includes the Proto-Indo-European root word "ghre," meaning "to grow." Ghrelin is produced in the hypothalamus, kidney and pituitary gland, but most of it is synthesized in and released by the stomach. The picture below (credit to Rae Silver, Joseph LeSauter and Donald Pfaff) shows a photomicrograph of the stomach wall. The hormone ghrelin has been specifically tagged and can be seen in the form of black dots.



Ghrelin has many actions, but the most prominent one is that it increases hunger by stimulating neurons in the arcuate nucleus of the hypothalamus, especially the neurons that express neuropeptide Y and agouti-related protein. Neuropeptide Y and agouti-related protein are both potent stimulators of appetite. Not only that, neuropeptide Y and agouti-related protein also enhance appetite by reducing the action of the appetite inhibitor proopiomelanocortin. As might be expected, people who are given injections of ghrelin become voraciously hungry and eat more than they otherwise would.

Ghrelin does have a specific role in the energy management of the body. Researchers at Columbia and Rockefeller Universities have shown that ghrelin is released in a circadian manner, prior to the onset of mealtimes. This pattern is illustrated in the graph below.

Just before mealtime, ghrelin is released from the stomach and acts on the hypothalamus to induce food-seeking behavior. In some ways this is a very adaptive mechanism. Rather than allowing a person to continue various activities and deplete energy stores, ghrelin acts to remind us to start seeking food and begin preparing for a meal. As soon as food reaches the stomach, ghrelin levels drop dramatically and stay low until an hour or so before the next meal is normally eaten.

Because of ghrelin's role in enhancing hunger, it is a prominent target of anti-obesity strategies. However, counteracting ghrelin has proved harder than one might expect. When a large part of the stomach is removed in weight loss surgery, ghrelin levels do drop in the short term. However, within a year post-surgery, ghrelin production recovers and patients tend to have higher blood levels of ghrelin than they did before the surgery. Even when mice are bio-engineered to lack the ability to produce any ghrelin whatsoever, their body weight gain and 24-hour food intake remain unaffected, suggesting that there are redundant appetite control systems that promote food intake in spite of the fact that ghrelin levels have been reduced to zero.

Although ghrelin-related strategies for hunger control do not look promising at this time, knowing about this hormone can still help us on a cognitive level. When the clock is moving toward lunch or dinner-time and we find ourselves obsessing about food, it's good to know that we aren't actually starving. We are simply getting a signal from our stomachs that it is time to start foraging for food. Because most of us live in a situation where food is as close as the nearest refrigerator or pantry, we can smile and tell ourselves that all is well. Thanks to modern civilization, we won't have to pick up a spear and run down an unsuspecting wild animal or rush out to gather roots and berries. The food will be there when it's needed, and we can calmly go back to our activities until it is time to eat.

Essential Carbohydrates

The most obvious characteristic of a low-carb diet is that it is low in carbohydrates. The original Atkins diet recommends that dieters start its Induction phase with essentially zero grams of carbohydrates. The 2002 version of the Atkins diet allows dieters to do Induction with up to twenty grams of carbohydrates. The Protein Power diet begins its Phase I Intervention stage at thirty grams of carbohydrates. As all of these diets progress, additional carbohydrates are introduced in a controlled manner, but even at maintenance, most low-carbers eat no more than 100 grams of carbohydrate per day.

By contrast, the US Department of Agriculture recommends that both children and adults eat 45-65% of their daily calories as carbohydrates. That can mean well over 300 grams of carbohydrates per day for a person consuming a 2000 calorie diet.

What happens if we ignore the USDA guidelines and don't eat enough carbs every day? Carbohydrates are popularly thought to be essential for providing energy. Specifically they are thought to be necessary to provide fuel for the brain and to refill stores of glycogen in muscles and in the liver.

The American Diabetes Association tells us that the brain and central nervous system normally have a daily requirement of about 130 grams of carbohydrate in the form of glucose. However, after a period of adaptation, most of these tissues are also able to use ketones as an energy source. This reduces the carbohydrate requirement to about 30 grams of glucose per day. As low-carbers with Ketostix already know, ketones are produced in abundance from the fats and amino acids consumed on a low-carb diet. The remaining need for thirty grams of glucose can easily be met through a metabolic pathway called gluconeogenesis, which allows the body to use amino acids from proteins and the glycerol backbones from fats to synthesize glucose in the absence of any carbohydrate intake.

Glycogen, which is a storage form of glucose, can similarly be replenished by the glucose made through gluconeogenesis. As far as the general energy requirements of the body, these can be met very efficiently both by the utilization of dietary fat and by the mobilization of stored fat.

Carbohydrates, therefore, are not an essential element of a healthy diet. There are essential fats, which include the omega-3 and omega-6 fatty acids. Because they are not produced by the body, omega-3 and omega-6 fatty acids must be consumed in order to ensure the normal function of the nervous system, heart and immune system. There are essential amino acids, including isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan and valine. Although some amino acids can be synthesized by the body, these eight cannot. Unless they are ingested, and ingested in the proper amounts, the body is unable to assemble all of the structural and enzymatic proteins that are needed to sustain life.

By contrast, there is no disease state associated with an insufficient intake of carbohydrates. It is true that the body needs carbohydrates for energy within certain types of tissues, for synthesis of the backbones of DNA and RNA, and for signaling purposes, but it is well able to synthesize all of these from the raw materials provided by the amino acids in the proteins we eat.

For those of us raised on the dogma of eating low-fat and high-carb, this is hard to believe. But if we think about our caveman ancestors, we realize that they didn't have access to pasta, potatoes or rice, or even high-carb fruits and vegetables on a regular basis. They were able to survive and reproduce without a high carbohydrate intake because, amazingly enough, there is no such thing as an essential carbohydrate.

Welcome, New Low-Carbers!

You'd been hoping to lose weight all through 2009, but never quite managed it. Then came Thanksgiving. After the big meal and the family time, you washed the dishes, put away the leftovers, dug out the Christmas decorations, and as you made the house ready for the season you hoped to do better in December. Of course, you had forgotten about the holiday goodies that would be brought into your office as treats for everybody. They sat there in all their deliciousness, and it was just too hard to resist them.

Christmas arrived. Only Scrooge would decline the traditional foods that various relatives and friends had prepared. A week of polishing off the remaining treats has left you with a closet of clothes that no longer fit and a temptation to try a weight-related New Year's resolution one more time.

What makes your 2010 resolution different from your previous weight-loss resolutions? This time you're doing low-carb! You have gone to the Internet to investigate low-carbing and to make contact with people who can encourage and advise you. You have a book (Dr. Atkins' Diet Revolution or Mike and Mary Dan Eades' Protein Power), and you have decided to read it and follow what it says.

What's different about low-carbing? Low-carbing allows us to work with the way our body works rather than fighting against it. When we eat foods with lots of carbs (bread, pasta, potatoes, most desserts and snacks), our bodies can't use all of those calories at once. Our pancreas releases the hormone insulin to store the nutrients in our cells. Between meals, the nutrients are released and are used for energy.

However, as we age, the store-and-release cycle sometimes starts to break down. We eat the carbs and store the nutrients, but when it comes time for our cells to release the nutrients, they resist doing so. The body needs energy but the cells don't want to release it. So the body moves to plan B. It commands us, "EAT MORE." Sure enough, we load up on more carbs and for a little while we have the energy we need. The excess energy from our snack is stored in our cells, but once again the cells resist releasing it when we need more energy a few hours after we've eaten. As this vicious cycle deepens, we notice that we are eating, getting hungry, eating again, getting hungry again and steadily gaining weight. We can try ignoring our appetite, but our bodies are clever. They will make the drive for food relentless. If our willpower holds, our bodies will assume they are in a starvation situation and will retaliate. They will throttle down our core temperature and make us less energetic. Sound familiar?

Low-carb eating circumvents the broken store-and-release cycle. Eating low-carb food means we will be eating mostly protein and fat. Both protein and fat are stored after meals, but the process is more gradual. With very few carbs, less insulin is needed, and this means that body's cells are more likely to make the switch from storage mode to release mode between meals. The presence of dietary fat (in the absence of carbs) will signal the cells that starvation is not imminent, and will tell the body that there is no need to lower body temperature and energy level.

What about calories? When our body is utilizing its own stored energy, it will naturally adjust our appetite to be content with a lower calorie intake. That's hard to believe, but most people will spontaneously start eating less as they become adapted to a low-carb way of eating. They are no longer putting a part of each meal into permanent storage, and are actually able to mobilize the energy their body has been hoarding against what it thinks is a famine. With low-carbing, self control is necessary when it comes to food choices, but the constant battle against raging hunger is over.

That's it in a nutshell. The practice is harder than the theory, but that's why the books by Dr. Atkins and the Eades are there. Psychological support is available from online bulletin boards such as Low Carb Friends.

You can do it. Your body will actually help you when you work with it rather than against it. And those clothes in your closet will soon be too big rather than too small. Happy Low-Carb Year!