In his post last Friday, Peter did a very nice job of introducing the the counter-intuitive idea that having too little fat, rather than too much, causes many of the metabolic problems of obesity. Today I thought it would be good to continue on with this theme and to focus on some of the mechanisms that explain this strange relationship. Let’s begin where Peter ended off:
Currently, the emerging theory of why obesity is associated with metabolic disease risk suggests that it is not the excess amount of fat that results in problems – but rather, it is the inability of the fat tissue (specifically subcutaneous) to expand enough via the development of numerous, healthy adipocytes or fat cells to store all the excess calories being ingested.
Fat tissue is made up of many small fat cells, called adipocytes, each of which stores a single droplet of lipid. When we say that there are problems with having too little fat, we really mean that there are problems with having too few adipocytes. For the purposes of this discussion, the most important categories of adipocytes are subcutaneous (those found just below the skin), visceral (those found inside of the abdominal wall) and intermuscular (between muscles). I’ve taken the figure below from my Master’s thesis, which shows where each of these types of cells can be found within the body.
What’s interesting about these different types of adipocytes is that they differ in their rates of lipolysis – essentially how rapidly they release fat into the blood stream. In comparison to subcutaneous adipocytes, visceral adipocytes have higher rates of lipolysis and decreased sensitivity to the anti-lipolytic effects of insulin. What this means is that visceral adipocytes are very quick to give up the fat they store, while subcutaneous adipocytes (especially those found in the lower body) hold onto fat, and really resist letting it into the bloodstream. When visceral adipocytes give up their fat, it circulates through the bloodstream where it can accumulate within the liver, heart, and skeletal muscle, resulting in insulin resistance and metabolic dysfunction. In contrast, subscutaneous adipocytes hold tightly onto their fat, preventing it from doing any damage to the rest of the body (click here for a fantastic in-depth review of the differences between visceral and subcutaneous adipose tissue by Bernardo Wajchenberg).
Let’s say that you’re a lean, healthy individual, but for one reason or another you begin to consume more calories than you burn. You are going to start storing fat in your subcutaneous adipocytes. As Peter suggested, so long as you are able to continue storing fat in those subcutaneous adipocytes, you are likely to be metabolically healthy. However, if you continue to gain weight, you will eventually exceed the storage capacity of your subcutaneous adipocytes, at which point fat will start to “overflow” into visceral adipocytes. As mentioned earlier, these visceral adipocytes already have high rates of lipolysis, which is bad enough. But as they enlarge, visceral adipocutes become increasingly insulin resistant, resulting in the release of even higher amounts of fat into the bloodstream, rapid accumulation of fat within the liver and other organs, and increased metabolic risk.
The simple differences in visceral and subcutaneous adipocytes can help to make sense of the “outliers” that Peter discussed in his post on Friday. Individuals with lipodystrophy (who have very few adipocytes) appear lean, but with no place to safely store their fat, it rapidly accumulates within the heart, liver, and muscles, resulting in increased health risk. Similarly, TZD treatment results in an increase in the number of subcutaneous adipocytes, which essentially suck up circulating lipid and reduce metabolic risk accordingly. This is also why it can be so difficult to reduce the amount of fat stored in your hips and thighs – those subcutaneous adipocytes just do not want to release the fat that they are storing! It may be frustrating, but it’s terrific from a health perspective!
So, what is the clinical utility of these differences? Unfortunately, not much. We really have no control over where we store our body fat. And the simple fact is that most obese individuals have large amounts of visceral fat, resulting in increased health risk. But I still find it incredibly interesting that, far from being the scourge that people often expect, fat cells are actually extremely important to the healthy function of the human body.