Thursday, May 5, 2011

Fat cells: Is it the size or the number?

Obesity is tightly associated with virtually all "western diseases," including high blood pressure, diabetes, gout, and dyslipidemia.  Insulin resistance (type 2 diabetes) is similarly associated with these diseases.  This is why researchers have begun to use the literary gem and public health nightmare "diabesity" when referring to our current health epidemic.  Thus, researchers are diligently trying to tease apart the associations and mechanisms that explain diabesity.
Veilleux and colleagues published a study in this month's issue of Diabetes looking at the predictive power of the size and number of adipocytes (fat cells) on markers of dyslipidemia ("poor blood lipids").     They found that the enlargement of abdominal adipocytes was independently associated with changes in blood lipids consistent with the metabolic syndrome.

Source: flickr
Above is a photomicrograph of adipocytes.  The dark splotches are the nuclei of the cells.  The big white space?  That's a large lipid droplet.  Adipocytes store fat to be used for energy, and as you can see, they are very good at what they do.  Our fat stores can increase by either enlargement of the adipoctyes or an increase in the number of adipocytes, or as is common in biology, a combination of the two. And all of these cells aggregrate to form different fat depots in the body.  
Two of the main fat stores are subcutaneous fat - meaning under the skin - and omental fat, which rests behind the abdominal wall.  The gynoid, or "pear shape," fat distribution refers to subcutaneous fat distributed around the hips and buttucks, and it is associated with a decreased risk of dyslipidemia.  Android, or "apple shape," fat distribution refers to abdominal obesity, and is associated with an increased risk of dyslipidemia.  But remember, a large gut is composed of both subcutaneous fat and omental fat; both tend to increase together but it is the omental that seems the most deleterious.
Abdominal subcutaneous fat
Source: FreeDigitalPhotos

Peripheral subcutaneous fat
Source: FreeDigitalPhotos

Given the known complications of body fat, researchers wanted to look to see if the association between omental fat and dyslipidemia was more closely related to enlarged adipocytes or a higher number of adipocytes, independent of fat distribution or fat mass.  Obese women who were undergoing surgery had biopsies taken of their omental and subcutaneous fat.  These biopsies were then used to categorize the women by adipocyte hypertrophy (enlargement) or hyperplasia (high cell count) for both subcutaneous and omental fat stores.  Blood markers for dyslipidemia - particularly representing hypertriglyceridemia, or elevated triglycerides, were then coupled with the adipocyte data to develop a predictive model - that is, how do adipocyte characteristics predict dyslipidemia.

The most pronounced finding was that sufficiently large omental adipocytes increased the risk of hypertriglyceridemia by 4-fold, whereas sufficiently many omental adipocytes only increased the risk by 1.5-fold.  The size or number of subcutaneous adipocytes showed no increased risk of elevated triglycerides.  These changes in risk were seen after several factors had been adjusted for - such as body fat mass, BMI, and others - and so represent the independent contribution of these adipocyte characteristics.  The enlarged omental adipocyte group further demonstrated dyslipidemia in other triglyceride-related blood markers, although the results were less dramatic.

Figure: Conceptual representation of the results
And perhaps you are wondering, do enlarged omental adipocytes cause the dyslipidemia?  Does the dyslipidemia cause the enlarged adipocytes?  Or is there something else that causes them both to occur in lockstep?  An interesting piece to the puzzle is that surgical removal of omental fat does not improve dyslipidemia.  Or only seems to do so in the short-term when it is accompanied with the already-shown-to-do-so gastric bypass surgery (article on recent findings).  Those data would indicate that it is not the omental fat that causes the dyslipidemia.  But given the Veilleux study we just discussed, perhaps surgical removal would work if the patients had predominately large omental adipocytes, rather than many.  

While it's well known that obesity is tightly associated with dyslipidemia and metabolic syndrome, these data are the first to specifically examine adipocyte "cellularity" with metabolic derangement in obese women.  Admittedly, this experiment is more interesting from a physiological or mechanistic standpoint - everyone knows that abdominal obesity is both unhealthy and no one is happy with their "gut" regardless of the cellular mechanism.  So while we wait for that eventual discovery, let's agree to keep our visceral fat cells both small and few.

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