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The case of visceral fat: argument for the defense
Samuel Klein
Center for Human Nutrition and Division of Geriatrics and Nutritional Sciences, Washington University School of Medicine, St. Louis, Missouri, USA.
Address correspondence to: Samuel Klein, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8031, St. Louis, Missouri 63110, USA. Phone: (314) 362-8699; Fax: (314) 362-8230.
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Published June 1, 2004 - More info
J Clin Invest. 2004;113(11):1530–1532. https://doi.org/10.1172/JCI22028.
© 2004 The American Society for Clinical Investigation
The relationship between excess abdominal fat mass and insulin resistance was recognized a half century ago, when Jean Vague, a French physician, reported an association between a “masculine” or “android” obesity phenotype and diabetes (1). Subsequently, many large epidemiological and smaller physiological studies have confirmed the relationship between abdominal obesity and insulin resistance, diabetes, and other metabolic risk factors for coronary heart disease (2–5). In fact, excess abdominal fat is even associated with impaired insulin-mediated glucose uptake in lean adults (6).
Abdominal fat is composed of several distinct anatomic depots: subcutaneous fat, which can be divided into anterior and posterior or superficial and deep layers, and intraabdominal fat, which can be divided into intraperitoneal and retroperitoneal sites. Intraperitoneal fat, also known as visceral fat, is composed of mesenteric and omental fat masses. Although the absolute amount of each of these depots is much larger in upper-body obese than in lean persons, the relative amount of abdominal fat with respect to total body fat mass is often similar in both groups. For example, visceral fat constitutes about 10% of total body fat mass in lean and obese men (7).
The close relationship between abdominal fat (i.e., total, subcutaneous, and/or visceral fat) and metabolic disease has stimulated a clinical interest in identifying high-risk patients. Waist circumference is often used as a surrogate marker of abdominal fat because it correlates closely with total abdominal fat mass measured by computed tomography (8) and it is not practical to directly measure abdominal fat mass in a clinical setting. Based on data from epidemiological studies, the Expert Panel on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults, convened by the NIH, proposed that men with a waist circumference greater than 102 cm (40 in.) and women with a waist circumference greater than 88 cm (35 in.) are at increased risk for metabolic diseases (9).
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Portal and systemic fatty acid kinetics
In this issue of the JCI, Nielsen and colleagues report the results of a study that sheds new light on portal and systemic fatty acid kinetics in human subjects (20). By using sophisticated tracer methods in conjunction with mathematical modeling and technically demanding catheterization procedures, these investigators evaluated regional leg and splanchnic (intestine, spleen, pancreas, liver, and visceral fat) FFA metabolism and were able to determine the relative contributions of FFAs released from visceral fat into the portal and systemic circulations in lean and obese men and women (summarized in Figure 1).
Figure 1Approximate relative contributions of FFAs released from lower- and upper-body subcutaneous fat depots and from splanchnic tissues to the systemic venous circulation, and FFAs from visceral fat and the systemic arterial circulation to the portal circulation in lean and obese subjects. Values are based on data from ref. 20.
The results of this study demonstrate that the release of FFAs into the portal vein from lipolysis in visceral fat depots increases with increasing amounts of fat (20). However, the relative contribution at any individual visceral fat mass was quite variable. For example, in subjects with approximately 150 cm2 of visceral fat, the percentage of total FFAs delivered to the liver that were derived from visceral fat ranged from 0% to 45%, and the relative contribution of FFAs from visceral fat was lower in some subjects with a larger amount of visceral fat (about 300 cm2) than it was in others with a small amount (about 10 cm2). Therefore, although there is a direct relationship between visceral fat mass and its contribution to hepatic FFA metabolism, it is impossible to determine which individuals have a high rate of visceral FFA flux based on analysis of body composition and fat distribution alone. More importantly, the relative amount of portal vein FFAs derived from visceral fat was much less than the relative amount derived from lipolysis of subcutaneous fat. Subcutaneous adipose tissue depots release fatty acids into the venous circulation, which are then transported to splanchnic tissues by the arterial circulation. Only 5–10% of these fatty acids are metabolized by nonhepatic splanchnic tissues, and the rest enter the portal vein (21). Nielson and colleagues found that only approximately 5% and 20% of portal vein FFAs originated from visceral fat in lean and obese subjects, respectively (Figure 1). The effect these additional fatty acids may have on insulin action in the liver is not known, but these data demonstrate that visceral fat is not as important as subcutaneous fat in supplying FFAs to the liver in lean or in most obese persons.
If fatty acids released from visceral fat contribute to insulin resistance in skeletal muscle, these FFAs must escape metabolism by the liver and enter the systemic circulation. Nielsen and colleagues found that only about 6% and 14% of the total FFAs that appear in the systemic circulation in lean and obese subjects, respectively, enter from the hepatic veins draining the liver (Figure 1) (20). Moreover, most of the fatty acids that pass through the liver are derived from lipolysis of subcutaneous fat, which releases FFAs that are ultimately delivered to the liver through the portal vein (about 80% of hepatic blood flow) and the hepatic artery (about 20% of hepatic blood flow). Therefore, very few fatty acids released from visceral fat itself are ever seen by skeletal muscle in either lean or obese individuals.
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