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Cited by 98Gut microbiota and healthAdipokines, Inflammation, and Metabolic DiseasesGastrointestinal motility and disorders

Role of the gut in visceral fat inflammation and metabolic disorders

Lam, Yan Y., Mitchell, Andrew J., Holmes, Andrew J., Denyer, Gareth S., Gummesson, Anders, Caterson, Ian D., Hunt, Nicholas H., Storlien, Len H.·2011·Obesity
DOI 10.1038/oby.2011.68
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Abstract

Obesity and diabetes are rapidly increasing in both developed and developing countries with enormous personal and economic cost implications. Type 2 diabetes was recognized over 20 years ago, in the seminal Banting Lecture of Reaven ((1)), as part of a cluster of metabolic disorders including obesity (defined by BMI (weight (kg)/height (m)2)), hypertension and dyslipidemia (high triglycerides and low high-density lipoprotein-cholesterol) and with cardiovascular disease as an endpoint (in both senses of the word). Since then, both central adiposity and circulating inflammatory markers (such as C-reactive protein) are understood to also be critical predictors in the metabolic syndrome. Key questions of major importance are: (i) Why is visceral fat particularly deleterious; (ii) What generates the chronic low-grade inflammatory profile of obesity; and (iii) Are these linked to a common etiology of metabolic dysregulation. Since the pioneering work from the laboratories of Kissebah ((2)) and Björntorp ((3)) following the observations of Jean Vague, there has grown an increasingly sophisticated understanding of the critical role of deep visceral fat in the development of metabolic syndrome. Whereas BMI does relate to metabolic dysfunction, waist-to-hip ratio, as a measure of central adiposity, is a better indicator of metabolic dysfunction and end stage cardiovascular risk (for example see refs. (2),(4)). Epidemiological work has shown that abdominal circumference correlates directly with metabolic dysfunction whilst an opposite, apparently protective, role of lower body fat was observed ((5)). With the development of nuclear magnetic resonance and computed tomography techniques it has then been possible to further delineate abdominal fat into subcutaneous versus visceral actually within the peritoneal cavity. Using nuclear magnetic resonance, Miyazaki and colleagues ((6)) related insulin-stimulated glucose disposal individually to these adipose compartments and showed a highly significant relationship between impaired glucose disposal and increased visceral fat but no such relationship with subcutaneous. More recent results from the Framington Heart Study provided strong epidemiological support over a range of metabolic variables ((7)). Indeed, an analysis from this study even suggested a modest protective effect of abdominal subcutaneous fat in individuals in the highest tertile of visceral fat ((8)). Finally, it is not only metabolic variables that relate to visceral fat accumulation. Visceral abdominal fat area, for example, is associated with an increase in the risk, prevalence and aggressiveness of certain types of cancers, particularly colon and colorectal ((9),(10)). Interestingly, a subset of obese individuals, classified as "metabolically healthy obese," account for ∼20% of the obese population ((11)). They are characterized by a lower visceral fat content, higher insulin sensitivity, and a favorable metabolic profile (lower triglycerides, inflammatory markers, and higher high-density lipoprotein-cholesterol) as compared to the "at-risk" obese population ((12)). Meigs and colleagues ((13)) reported that the prevalence of type 2 diabetes and cardiovascular disease is approximately six- and twofold higher, respectively in "at-risk" obese individuals as compared to those who exhibit a metabolically healthy obese-like phenotype. A recent review by Després and coworkers ((14)) summarizes the evidence for excess visceral adiposity as a predictor of insulin resistance and a "proatherogenic, thrombotic, and inflammatory profile" associated with increased cardiovascular disease risk and asks if this might not be the cholesterol of the 21st century. Defining various fat depots, both anatomically and metabolically, is critical to elucidate the origin as well as the metabolic sequelae of regional fat distribution. Functionally, adipose tissue is classified into brown and white adipose tissue, with the former dissipates energy through heat production whereas the latter stores energy as triglycerides. Advances in imaging technology enable further categorization of white adipose tissue into subcutaneous (directly beneath the skin) and visceral (within the peritoneal cavity) fat depots. The collective term of "visceral fat," however, should be interpreted carefully as this may under-represent the distinctiveness of the various fat depots in the peritoneal cavity. For instance, perirenal, omental, and mesenteric fat are all "visceral fat" but their different anatomical locations imply that their metabolism may differ from each other as a consequence of unique local stimuli. Visceral adipose tissues are also known to have depot-specific structures. For example, omental and mesenteric fat are characterized by the presence of lymph nodes that are nonexistent in the perirenal and gonadal depots ((15)). These lymph nodes may be an important determinant of the metabolic characteristics of the depots as recently demonstrated

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  • An impaired gut barrier increases the translocation of microbial metabolites, or even the microbes themselves, from the lumen of the gastrointestinal tract into adjacent tissues, and these materials enter the portal and systemic circulation, a phenomenon known as endotoxemia, to trigger inflammatory responses at the tissue level.

    “An impaired gut barrier (or a “leaky” gut) increases the translocation of microbial metabolites, or even the microbes themselves, from the lumen of the gastrointestinal tract into the adjacent tissues. These materials then enter the portal and systemic circulation, a phenomenon known as endotoxemia, to trigger inflammatory responses at the tissue level [97].”

    From Are the gut bacteria telling us to eat or not to eat? reviewing the role of gut microbiota in the etiology, disease progression and treatment of eating disorders (2017) · cites this paper as [97]

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Authors
Lam, Y. Y., Mitchell, A. J., Holmes, A. J., Denyer, G. S., Gummesson, A., Caterson, I. D., Hunt, N. H., & Storlien, L. H.
Affiliations
  • The University of Sydney (AU)
  • University of Gothenburg (SE)
Corresponding author
Lam, Yan Y.
ORCID
Venue
Obesity
Publisher
Wiley
Published
2011-11
Volume
19
Issue
11
Pages
2113-2120
ISSN
  • 1930-7381 (ISSN-L)
  • 1930-739X
DOI
10.1038/oby.2011.68
OpenAlex
W2044475165
Cited by
97
References
101
Citations by year
2026: 1 · 2025: 2 · 2024: 10 · 2023: 4 · 2022: 7 · 2021: 4 · 2020: 6 · 2019: 5 · 2018: 8 · 2017: 11 · 2016: 9 · 2015: 12 · 2014: 5 · 2013: 6 · 2012: 5
FWCI
0.52
Type
journal article
Language
en
Open access
closed
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor, 310 d)
Locations
  • Obesity (publishedVersion)
  • PubMed (publishedVersion)
  • The Sydney eScholarship Repository (The University of Sydney) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
Keywords
gut microbiota, visceral fat, adipose tissue inflammation, metabolic disorders
MeSH terms
Animals, Humans, Inflammation, Macrophages, Metabolic Diseases, Obesity, Endotoxemia, Gastrointestinal Tract, Intra-Abdominal Fat, Body Fat Distribution, Metagenome

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