Critical Visceral Adipose Tissue Theory

I found this article almost a year ago, posted it on an LC discussion board, and was mostly greeted with silence so I had sort of forgotten about it.  In any case, I was reminded of the article while recently reading LynMarie's latest post on her blog:  Fat Fails First?  (Incidentally, that post corresponds well with my own recent offering on the topic:  The Progression of Insulin Resistance ).  

On to the subject of this post:  Role of a critical visceral adipose tissue threshold (CVATT) in metabolic syndrome: implications for controlling dietary carbohydrates: a review

There are likely many scenarios and pathways that can lead to metabolic syndrome. This paper reviews mechanisms by which the accumulation of visceral adipose tissue (VAT) may contribute to the metabolic syndrome, and explores the paradigm of a critical VAT threshold (CVATT). Exceeding the CVATT may result in a number of metabolic disturbances such as insulin resistance to glucose uptake by cells. Metabolic profiles of patients with visceral obesity may substantially improve after only modest weight loss. This could reflect a significant reduction in the amount of VAT relative to peripheral or subcutaneous fat depots, thereby maintaining VAT below the CVATT. The CVATT may be unique for each individual. This may help explain the phenomena of apparently lean individuals with metabolic syndrome, the so-called metabolically normal weight (MONW), as well as the obese with normal metabolic profiles, i.e., metabolically normal obese (MNO), and those who are "fit and fat." The concept of CVATT may have implications for prevention and treatment of metabolic syndrome, which may include controlling dietary carbohydrates. The identification of the CVATT is admittedly difficult and its anatomical boundaries are not well-defined. Thus, the CVATT will continue to be a work in progress.

This hypothesis is consistent with men having historically higher risks of CVD while women seem to be catching up as obesity becomes more prevalent.  On average, women have more adipose tissue, and more SCAT so it seems we tend to have more metabolically benign "depots" in which to store excesses before it wreaks metabolic havoc in our VAT.  Men, OTOH, tend towards central fat deposition from the get go.

I have expressed this same theory as each of us having an individual "fill line" for our fat depots -- the metabolic derangement seems to manifest itself when we near and/or exceed that level.  

Figure 1.  Critical Visceral Adipose Tissue Threshold (CVATT). According to the hypothesis, there is an individual range for accumulating a critical amount of visceral adipose tissue (VAT). Insulin sensitivity is important for weight gain and accumulation of VAT. Once the critical VAT threshold (CVATT) is reached, insulin resistance occurs, which may be protective initially and impair further weight and fat gain. Continuation of VAT accumulation can lead to metabolic syndrome. However, only a modest weight loss (5–10 percent) with accompanying VAT loss can reverse the process.

Adipose Tissue, Adipocyte Size and MetS:  As discussed in my blog post referenced above, elevated NEFA levels precede the other derangements of MetS.   It is also well known that VAT is the more metabolically active fat vs. SCAT.  Fat mass increases by a combination of two processes -- filling pre-existing cells therefore increasing size and/or creating new cells by differentiating pre-adipocytes.  In the section titled "Implications of fat mass expansion" we learn that it is the "stuffed full" (hypertrophy) fat cells that become dysfunctional leading to metabolic derangement.  SCAT is more efficient at creating new, smaller (therefore properly functioning) adipocytes that readily take up free fatty acids and triglycerides to sequester them from circulation.  VAT is apparently less so, so when these adipocytes reach capacity they become insulin resistant.  It doesn't say so in the article, but as I've blogged on several times, perhaps the most key role of insulin in our bodies is to regulate NEFA levels by inhibiting release from fat cells.  When an adipocyte becomes insulin resistant, the insulin is less able to inhibit lipolysis, thus free fatty acids are released.

So chronic positive caloric balance --> fat deposition in SCAT (some in VAT) --> more and bigger SCAT cells until you near capacity --> SCAT-IR --> diversion of fat to more metabolically active VAT -->  increase in VAT cell size --> VAT cell dysfunction --> Metabolic Syndrome.   This seems to agree with the discussion in the article indicating VAT is usually the first fat to go with weight loss and why improvements in biomarkers are seen with the first 5-10% weight loss but not correlated much more with further weight loss.  I find this to be good news.  If one is obese but not able to maintain a significant amount of weight loss, maintaining a modest one may be all that's required to at least reduce risk of developing T2, etc.  It may be impossible to predict an individual's CVATT, but if we can monitor NEFA levels in the overweight, a threshold weight for CVD risk could be established early.  If NEFA are normal, this person's fat cells are functioning normally and keeping excesses where they are supposed to be.  If NEFA are elevated, this is the first indication of adipocyte dysfunction -- the person has reached their "fill line".