Critical Visceral Adipose Tissue Threshold (CVATT) what is it and how does it affect Metabolic Syndrome? Eric S. Freedland, MD,Boston University School of Medicine begins a multipart feature on what CVATT is and how it affects carbohydrate consumption.
Role of A Critical Visceral Adipose Tissue Threshold (CVATT) In Metabolic Syndrome:
Implications for Controlling Dietary Carbohydrates
Eric S. Freedland, MD
Boston University School of Medicine
Arguably, the major pathogenic factor in the metabolic syndrome is central obesity . While abdominal obesity is determined by the accumulation of both subcutaneous adipose tissue (SCAT) and visceral adipose tissue (VAT), the excess accumulation of VAT appears to play a more significant pathogenic role. VAT depots, located in the body cavity beneath the abdominal muscles, are composed of the greater and lesser omentum (peritoneum that is attached to the stomach and links it with other abdominal organs) and the mesenteric fat. A lesser amount of VAT is located retroperitoneally. In general, VAT accounts for up to 20 percent of total fat in men and 5-8 percent in women. The abdominal SCAT is located immediately beneath the skin and on top of the abdominal musculature.
The predominance of lower body fat is SCAT, most of which is stored in the femoral and gluteal regions . Abdominal obesity can reflect a predominance of flabby SCAT; a firm, only modestly enlarged waist line resulting from deep VAT pushing the abdominal musculature outward; or a combination of enlarged SCAT and VAT depots. With the advent of more precise imaging techniques, e.g., magnetic resonance imaging (MRI) , computed tomography (CT) , and ultrasound , it has become evident that the accumulation of VAT not only accompanies but antedates the onset of the components of the metabolic syndrome and related disorders, e.g., insulin resistance, hypertension , glucose intolerance , type 2 diabetes, and coronary heart disease .
To date, it has not yet been established that insulin resistance, i.e., resistance of cells to insulin’s effects, is responsible for the onset of the multiple risk factors associated with insulin resistance syndrome and subsequent development of atherosclerosis and cardiac events . In fact, National Cholesterol Education Program Adult Treatment Panel (ATP III) criteria for Metabolic Syndrome have been found to have a low sensitivity for predicting insulin resistance and may be better thought of as predictors for cardiovascular risk .
In a recent study of a large number of apparently healthy men and women of varying age, VAT area was significantly associated with all of the metabolic syndrome criteria as defined by the NCEP ATP III. This was independent of insulin sensitivity and SCAT area. Insulin sensitivity was found to be independently associated with the criteria for HDL cholesterol, triglycerides (TGs), and fasting plasma glucose (FPG). SCAT area was independently correlated with only waist circumference after adjusting for VAT area and insulin sensitivity . In addition, the study results showed that clinical assessments of increased waist size and TG levels are strongly associated with decreased insulin sensitivity and increased VAT in individuals with fasting FPG <6.4 mmol/L .
The term “metabolic syndrome” is now preferable to “insulin resistance syndrome,” and has a prevalence of 25 percent in U.S. individuals age >20, rising to >40 percent by age 60 . The importance of central obesity is well-recognized in the definitions of metabolic syndrome per the American College of Endocrinology, National Cholesterol Education Program Adult Treatment Panel (ATP III), European Group for the Study of Insulin Resistance, and World Health Organization (WHO) . However, even apparently lean individuals with normal BMIs can have a significant accumulation of VAT with increased risk factors for cardiovascular disease and diabetes (metabolically obese normal weight; MONW) . Meanwhile, obese individuals with large BMIs but relatively little VAT can present with normal metabolic profiles and a paucity of risk factors for metabolic syndrome, cardiovascular disease, and diabetes, i.e., the metabolically normal obese; MNO) .
Ectopic Fat Storage Syndrome
The ectopic fat storage syndrome hypothesis suggests that as adipocytes hypertrophy and reach their capacity for storing more fat, then additional fat from excess dietary lipids or calories is deferred to non-adipose tissues intracellularly, e.g. liver, skeletal muscle, heart, and the beta cells of the pancreas where they can exert toxic effects and dysfunction . This “lipotoxicity” may also be exacerbated by impaired oxidation of fat within tissues . Furthermore, adipose tissue is a major endocrine organ that secretes numerous polypeptide hormones and cytokines that are proinflammatory and proatherogenic. These play a major role in affecting insulin action in skeletal muscle and creating a low-grade state of inflammation and endothelial dysfunction . Compared to SCAT, VAT has been correlated more with endothelial dysfunction .
CVATT—A Working Hypothesis
It must be emphasized that the current proposal is a working hypothesis. Figure 1 describes a critical VAT threshold (CVATT) which is unique for a given individual and represents a range for the accumulation of a critical mass of VAT (CVATT) that when achieved, leads to the development of metabolic syndrome. Note that insulin sensitivity is important for weight gain and accumulation of VAT, and investigators have proposed that insulin resistance may actually, to a certain extent, be beneficial by protecting cells with already impaired fatty acid oxidation. Once the CVATT is reached, insulin resistance (IR) occurs, which may be protective initially . In addition to protecting against further weight and fat gain , insulin resistance prevents glucose and more fat from entering the cell and becoming preferentially oxidized. Hence, insulin resistance also allows intracellular fat already present within the cell to become oxidized rather than cause further damage through “lipotoxicity .”
Implications of VAT loss
It is encouraging that only a modest loss of 5-10 percent of body weight in obese patients is associated with preferential mobilization of VAT compared to SCAT, leading to simultaneous improvement in all metabolic markers of CHD risk. Such modest weight loss can prevent and reverse type 2 diabetes , and sustained weight loss in obese women results in a reduction in elevated inflammatory cytokine levels and an amelioration of endothelial dysfunction . Surgical removal of VAT may reduce insulin resistance and plasma insulin levels , while liposuction of SCAT does not confer metabolic benefits . Weight loss usually leads to VAT reduction as well as reduction of depots of fat in non-adipose organs, thereby improving insulin sensitivity . However, once individuals improve insulin sensitivity by losing weight and crossing beneath their CVATT , they may now be more susceptible to weight gain and struggle to maintain this new state.
With total weight loss, those with greater amounts of VAT initially lose more VAT, and VAT is more sensitive to weight reduction because the VAT adipocyte is more metabolically active and sensitive to lipolysis . After the initial weight loss, further dietary restriction may lead to an overall reduction in body fat, rather than specific loss from a particular site. The metabolic improvements observed with only modest reductions in total weight underscore the importance of VAT in insulin resistance and metabolic abnormalities . Once the individual has lost a significant amount of VAT and is now below his CVATT, improvement in insulin sensitivity does not bear a linear relationship to the magnitude of weight loss .
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. While there are numerous studies linking VAT quantity to insulin resistance and metabolic syndrome, this does not necessarily prove that VAT is the cause. However, there are a number of plausible mechanisms linking VAT to the metabolic syndrome.
Eric S. Freedland, MD graduated from University of Rochester School of Medicine in 1982, trained in internal medicine at Mt. Auburn Hospital in Cambridge, MA, and emergency medicine at Harbor-UCLA Medical Center in Torrance, CA, and has held faculty positions at Harvard Medical School (1990-1991) and Boston University School of Medicine (1992-1997). Dr. Freedland has developed a nutrition-centered model of disease with a special emphasis on diabetes. A staunch advocate for prescribing lifestyle changes before drugs, Dr. Freedland has written and lectured extensively on this subject.
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