The Fat Storage Control Mechanism

The only way to successfully loose weight is to modify or turn off the mechanisms that stimulate fat storage.  For years we have been told that this was just a problem of thermodynamics, meaning the more calories you eat, the more calories you store. The solution was, thereby, eat less calories or exercise more, or both. We are taught in school that a 1 gram of carbohydrate contains 4 kcal, 1 gram of protein contains 4 kcal, and 1 gram of fat contains 9 kcal.

It’s easy to see that if I’m going to limit my calories, cutting out fat is the first step.  For the last 65 years, we as a society have been doing just that, cutting out fat, exercising more and eating fewer calories.  What has it done for us? It’s made us fatter! (1)

World Obesity Rates

Obesity Rates Around the World

Some may argue that we really aren’t eating fewer calories and exercising more. But most people I have seen in my office have tried and tried and tried and failed and failed and failed to loose weight with this methodology. The definition of insanity is “doing the same thing over and over and expecting a different result.”

Most of my patients are not insane, they recognize this and stop exercising and stop restricting calories . . . ’cause they realized, like I have, that it just doesn’t work! If you’re one that is still preaching caloric restriction and cutting out fat, I refer you to the figure above and the definition of insanity . . .

So, if reducing the calories in our diet and exercising more is not the mechanism for turning on and off the storage of fat, then what is?

Before I can explain this, it is very important that you appreciate the difference between triglycerides and free fatty acids.  These are the two forms of fat found in the human body, but they have dramatically different functions.  They are tied to how fat is oxidized and stored, and how carbohydrates are regulated.

Fat stored in the adipose cells (fat cells) Triglycerides-and-Glycerol1as well as the fat that is found in our food is found in the form of triglycerides. Each triglyceride molecule is made of a “glyceride” (glycerol backbone) and three fatty acids (hence the “tri”) that look like tails. Some of the fat in our adipose cells come from the food we eat, but interestingly, the rest comes from carbohydrates

(“What! Fat comes from sugar?! How can this be?!!“)

de novo lipogenesis

De Novo Lipogenesis

We all know that glucose derived from sugar is taken up by the cells from the blood stream and used for fuel, however, when too much glucose is in the blood stream or the blood sugar increases above the body’s comfort zone (60-100 ng/dl), the body stores the excess. The process is called de novo lipogenesis, occurring in the liver and in the fat cells themselves, fancy Latin words for “new fat.”  It occurs with up to 30% (possibly more if you just came from Krispy Kream) of the of the carbohydrates that we eat with each meal.  De novo lipogenesis speeds up as we increased the carbohydrate in our meal and slows down as we decrease the carbohydrate in our meal. We’ve known this for over 50 years, since it was published by Dr. Werthemier in the 1965 edition of the Handbook of Physiology (2).

While we know that fat from our diet and fat from our food is stored as triglyceride, it has to enter and exit the fat cell in the form of fatty acids.  They are called “free fatty acids” when they aren’t stuck together in a triglyceride.  In their unbound state, they can be burned as fuel for the body within the cells. I like to think of the free fatty acids as the body’s “diesel fuel” and of glucose as the body’s version of “unleaded fuel.”  The free fatty acids can easily slip in and out of the fat cell, but within the adipose cell, they are locked up as triglycerides and are too big to pass through the cell membranes.  Lipolysis is essentially unlocking the glycerol from the free fatty acids and allowing the free fatty acids to pass out of the fat cell. Triglycerides in the blood stream must also be broken down into fatty acids Insulin and Triglyceridesbefore they can be taken up into the fat cells. The reconstitution of the fatty acids with glycerol is called esterification. Interestingly, the process of lipolysis and esterification is going on continuously, and a ceaseless stream of free fatty acids are flowing in and out of the fat cells.  However, the flow of fatty acids in and out of the fat cells depends upon the level of glucose and insulin available. As glucose is burned for fuel (oxidized) in the liver or the fat cell, it produces glycerol phosphate. Glycerol phosphate provides the molecule necessary to bind the glycerol back to the free fatty acids. As carbohydrates are being used as fuel, it stimulates increased triglyceride formation both in the fat cell and in the liver, and the insulin produced by the pancreas stimulates the lipoprotein lipase molecule to increased uptake of the fatty acids into the fat cells (3).

So when carbohydrates increase in the diet, the flow of fat into the fat cell increases, and when carbohydrates are limited in the diet, the flow of fat out of the fat cells increases.

Summarizing the control mechanism for fat entering the fat cell:

  1. The Triglyceride/Fatty Acid cycle is controlled by the amount of glucose present in the fat cells (conversion to glycerol phosphate) and the amount of insulin in the blood stream regulating the flow of fatty acid into the fat cell
  2. Glucose/Fatty Acid cycle or “Randle Cycle” regulates the blood sugar at a healthy level.  If the blood glucose goes down, free fatty acids increase in the blood stream, insulin decreases, and glycogen is converted to glucose in the muscle and liver.

These two mechanisms ensure that there is always unleaded (glucose) or diesel fuel (free fatty acids) available for every one of the cells in the body. This provides the flexibility to use glucose in times of plenty, like summer time, and free fatty acids in times of famine or winter when external sources of glucose are unavailable.

The regulation of fat storage, then, is hormonal, not thermodynamic. Unfortunately, we’ve know this for over 65 years and ignored it.

We’ve ignored it for political reasons, but that’s for another blog post . . .

References:

1. James, W. J Intern Med, 2008, 263(4): 336-352

2. Wertheimer, E. “Introduction: A Perspective.” Handbook of Physiology. Renold & Cahill. 1965.

3. Taubs, G. “The Carbohydrate Hypothesis, II” Good Calorie, Bad Calorie. Random House, Inc. 2007, p 376-403.

9 Comments on “The Fat Storage Control Mechanism

  1. For the last 65 years, we as a society have been doing just that, cutting out fat, exercising more and eating fewer calories. What has it done for us? It’s made us fatter!”
    The bolded part never happened. See http://racingweight.com/blog/dont-blame-the-dentist-for-your-cavities/ and http://www.ers.usda.gov/ImageGen.ashx?image=/media/179798/carbs_intake_ers.png&width=450

    We as a society ate more junk, thanks to subtle marketing forces. See http://vimeo.com/67977038 (it’s an hour long, but well worth watching).

    Cheers, Nige

    • I keep reading studies of food consumption (in the UK) that find a decline in calorie intake over the years. They then re-affirm the calorie hypothesis, note the increasing obesity and conclude that it must be due to inactivity. They don’t find gluttony, so blame sloth without measuring it.

      Separate studies fail to find significant declines in energy expenditure.

    • Nigel, I never said there was a shortage of G3P… Not sure where your coming from. The liver makes ~240g of glucose every day no matter what you eat, so the glycerol phosphate will be there.

  2. “However, the flow of fatty acids in and out of the fat cells depends upon the level of glucose and insulin available.” implies that dietary carbohydrates are necessary for the storage of dietary fat in adipocytes i.e. Gary Taubes’ (Wrong) Insulin/Carbohydrate Hypothesis Of Obesity, to which you referred in Ref. 3.

    Dietary fat can be stored in adipocytes in the absence of a glucose and/or insulin spike i.e. eating fat can make you fat. In practice, no humans consume a diet approaching 100%E from fat (although brown bears fatten-up for winter hibernation by gorging on salmon heads), so it’s a moot point.

  3. Nigel, thank you for your comments. I implied that insulin and glycerol phosphate are the two rate limiting steps in lipogensis, not the carbohydrates themselves. Please do you homework on lipogenesis and the rate limiting chemical steps in triglyceride formation within the adipocyte. You can actually read the 1965 Handbook of Physiology (I quoted Taubs because he has the references to the original research in that chapter) to see the primary research behind this statement or you can read the 2002 article summarizing much of this here: http://diabetes.diabetesjournals.org/content/51/5/1493.full. I absolutely disagree with you about fat. Insulin must be present to store fat. That is why type I diabetics (fully insulin dependent) are very thin.
    I have been applying these dietary techniques personally and with my patients with dramatically successful results. I’ve read the literature. I’ve applied the science and it works. Before you claim that I am wrong, give me a primary literature reference disproving that these two are not the rate limiting steps, instead of a tertiary blog post of some unknown blogger who doesn’t have the courage to post her name or her references about that which she writes.

  4. Pingback: The Truth is . . . Caloric Restricted Exercise Won’t Work | Arizona Bariatric Institute

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