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Cited by 371Adipokines, Inflammation, and Metabolic DiseasesCardiovascular Disease and AdiposityAdipose Tissue and Metabolism

Why Visceral Fat is Bad: Mechanisms of the Metabolic Syndrome

Bergman, Richard N., Kim, Stella P., Catalano, Karyn J., Hsu, Isabel R., Chiu, Jenny D., Kabir, Morvarid, Hucking, Katrin, Ader, Marilyn·2006·Obesity
DOI 10.1038/oby.2006.277
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Abstract

A consensus has emerged that fat stored in the central segment of the body is particularly damaging in that it portends greater risk for diabetes, cardiovascular disease, hypertension, and certain cancers ((1), (2), (3)). It is also accepted that insulin resistance is a related characteristic that may be an essential link between central fat and disease risk. Additionally, it is possible that the hyperinsulinemia that accompanies insulin resistance in non-diabetic but at-risk individuals may magnify, or even mediate, some of the detrimental effects of visceral adiposity ((4), (5), (6)). However, there is less information regarding the mechanisms that may link visceral fat with risk for disease. For example, there is controversy regarding the specific mechanisms by which fat in the visceral compartment confers greater risk than subcutaneous fat. Many investigators have suggested that one or more moieties secreted by the visceral adipocyte might mediate insulin resistance. Among the so-called “bad actors” are free fatty acids (FFAs)11 Nonstandard abbreviations: FFA, free fatty acid. themselves (“portal theory”) ((7), (8), (9)) or the adipose tissue—released cytokines (adipokines) such as interleukin-1, interleukin-6, tumor necrosis factor-α, resistin, or a reduction in adiponectin, which has been repeatedly shown to be associated with reduced insulin resistance ((10), (11), (12), (13)). Of course, insulin itself could be involved, as other adipose-secreted protein compounds not yet identified. But why visceral fat? Is it because of the unique anatomical position of the visceral fat depot, with effluent entering the liver, or is it because of molecular characteristics of visceral fat itself, which may favor release of damaging molecules into the systemic circulation? These questions remain unanswered. However, in our laboratory, we have developed the obese dog model, which has led to some understanding of the pathogenesis of the metabolic syndrome. The dog model has not been widely used for the study of the metabolic syndrome, but we have found it to have several important characteristics that we have been able to exploit: the ability to make longitudinal measurements and the ability to access the portal vein. In that sense the dog is a unique model, in that these latter measurements are daunting in rodents, and carrying out repetitive, invasive clinical measurements in non-human primates is challenging. Also, the dog with visceral obesity has turned out to be a reasonable model for a similar syndrome in humans (Figure 1). In fact, the dog is genetically more similar to humans than is the rodent. Different animal models of obesity and their relative homology to the human genome. Here we summarize a significant amount of evidence in which we examined what we considered to be the simplest hypothesis composed of two postulates: 1) that FFAs per se are among the most important products of the visceral adipocyte to cause insulin resistance (and hence the metabolic syndrome) and 2) that the anatomical position of the visceral adipose depot (i.e., portal drainage into the liver) plays an important role in the pathogenesis of the metabolic syndrome. While we cannot say that these postulates are proven, there are data that support them, and Occam's razor instructs us to accept them until proven untrue. Whether true or not, it appears that examining them has led us to a deeper understanding of the physiological basis for the metabolic syndrome itself. One similarity between dogs and humans is the wide variance in fat deposition in a “wild” or “natural” population. We measure distribution of fat about the truncal region using magnetic resonance imaging [Figure 2; 11 axial slices: 1-cm landmark slice at the umbilicus (left renal artery) ± 5 cm]. Similar to human subjects ((14), (15)), there is surprising variability in distribution. Some animals are strikingly lean, with total fat varying over a factor of 5, from 10 to 50 cm3/cm3 non-fat tissue. Interestingly, there is a tendency for visceral adiposity to increase rapidly as one examines animals with increasing body fat; the visceral fat depot tends to plateau, and subcutaneous fat increases more rapidly with overall obesity. This tendency for visceral fat to increase and plateau may be responsible for the sharp reduction in insulin sensitivity in leaner individuals, with insulin resistance being similar in human subjects with BMI levels >30 kg/m2 ((16)). Illustration of fat distribution taken by magnetic resonance imaging in the truncal region in the dog model. The axial image at the level where the left renal artery branches from the abdominal aorta is used as the midpoint landmark slice. Contribution of omental vs. subcutaneous fat is assessed within the region ±5 cm from this landmark slice. Approximately 20 axial images (depending on the relative torso length of the animal) are used for assessment of total trunk fat. Regardless of basal adiposity, increasing the cont

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Authors
Bergman, R. N., Kim, S. P., Catalano, K. J., Hsu, I. R., Chiu, J. D., Kabir, M., Hucking, K., & Ader, M.
Affiliations
University of Southern California (US)
Corresponding author
Bergman, Richard N.
ORCID
Venue
Obesity
Publisher
Wiley
Published
2006-02
Volume
14
Issue
S2
Pages
16S-19S
ISSN
  • 1930-7381 (ISSN-L)
  • 1930-739X
DOI
10.1038/oby.2006.277
OpenAlex
W2003380115
Cited by
371
References
22
Citations by year
2026: 3 · 2025: 6 · 2024: 17 · 2023: 12 · 2022: 14 · 2021: 15 · 2020: 29 · 2019: 21 · 2018: 23 · 2017: 17 · 2016: 25 · 2015: 21 · 2014: 26 · 2013: 31 · 2012: 25
FWCI
11.72
Type
journal article
Language
en
Open access
closed
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor, 2409 d)
Locations
  • Obesity (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institute on Aging (AG0-0093)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK029867, DK27619, DK29867)
Topics
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
  • Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
Keywords
visceral fat, metabolic syndrome, insulin resistance, hyperinsulinemia, free fatty acids, adipokines, adiponectin, resistin, visceral obesity, portal vein, subcutaneous adipose tissue, diabetes mellitus, cardiovascular disease, hypertension, cancer risk, inflammation, obesity pathogenesis, animal models of human disease
MeSH terms
Animals, Haplorhini, Body Composition, Disease Models, Animal, Dogs, Humans, Obesity, Metabolic Syndrome, Intra-Abdominal Fat, Mice, Rats

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