Central Role of the Adipocyte in the Metabolic Syndrome
Abstract
Insulin resistance is associated with a plethora of chronic illnesses, including Type 2 diabetes, dyslipidemia, clotting dysfunction, and colon cancer. The relationship between obesity and insulin resistance is well established, and an increase in obesity in Western countries is implicated in increased incidence of diabetes and other diseases. Central, or visceral, adiposity has been particularly associated with insulin resistance; however, the mechanisms responsible for this association are unclear. Our laboratory has been studying the physiological mechanisms relating visceral adiposity and insulin resistance. Moderate fat feeding of the dog yields a model reminiscent of the metabolic syndrome, including visceral adiposity, hyperinsulinemia, and insulin resistance. We propose that insulin resistance of the liver derives from a relative increase in the delivery of free fatty acids (FFA) from the omental fat depot to the liver (via the portal vein). Increased delivery results from 1) more stored lipids in omental depot, 2) severe insulin resistance of the central fat depot, and 3) possible regulation of visceral lipolysis by the central nervous system. The significance of portal FFA delivery results from the importance of FFA in the control of liver glucose production. Insulin regulates liver glucose output primarily via control of adipocyte lipolysis. Thus, because FFA regulate the liver, it is expected that visceral adiposity will enhance delivery of FFA to the liver and make the liver relatively insulin resistant. It is of interest how the intact organism compensates for insulin resistance secondary to visceral fat deposition. While part of the compensation is enhanced B-cell sensitivity to glucose, an equally important component is reduced liver insulin clearance, which allows for a greater fraction of B-cell insulin secretion to bypass liver degradation, to enter the systemic circulation, and to result in hyperinsulinemic compensation. The signal(s) resulting in B-cell up-regulation and reduced liver insulin clearance with visceral adiposity is (are) unknown, but it appears that the glucagon-like peptide (GLP-1) hormone plays an important role. The integrated response of the organism to central adiposity is complex, involving several organs and tissue beds. An investigation into the integrated response may help to explain the features of the metabolic syndrome.
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Adipose tissue in obese people is insulin resistant, raising nonesterified fatty acid levels, worsening insulin resistance in muscle, and altering hepatic metabolism.
“Adipose tissue in obese people is insulin resistant, which raises nonesterified fatty acid levels, worsening insulin resistance in muscle 29,33 and altering hepatic metabolism 31 ;”
From Diagnosis and Management of the Metabolic Syndrome: An American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement (2005) · cites this paper as [31]
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- Authors
- Bergman, R. N., Van Citters, G. W., Mittelman, S. D., Dea, M. K., Hamilton-Wessler, M., Kim, S. P., & Ellmerer, M.
- Affiliations
- University of Southern California (US)
- From the Department of Physiology and Biophysics, Keck School of Medicine and University of Southern California Diabetes Research Center, Los Angeles, Calif
- Corresponding author
- Bergman, Richard N.
- Venue
- Journal of Investigative Medicine
- Publisher
- SAGE Publications
- Published
- 2001-01
- Volume
- 49
- Issue
- 1
- Pages
- 119-126
- ISSN
- 1081-5589 (ISSN-L)
- 1708-8267
- OpenAlex
- W1983548385
- Cited by
- 202
- References
- 29
- Citations by year
- 2026: 1 · 2024: 4 · 2023: 2 · 2022: 5 · 2021: 4 · 2020: 2 · 2019: 2 · 2018: 5 · 2017: 6 · 2016: 4 · 2015: 2 · 2014: 6 · 2013: 9 · 2012: 7
- FWCI
- 3.38
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Investigative Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (T32 AG 00093, T32AG000093)
- 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 › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
- Keywords
- metabolic syndrome, insulin resistance, visceral fat, free fatty acids, hepatic insulin resistance, hyperinsulinemia, glucagon-like peptide-1, dyslipidemia, type 2 diabetes
- MeSH terms
- Animals, Diabetes Mellitus, Type 2, Dietary Fats, Dogs, Fatty Acids, Nonesterified, Humans, Insulin Resistance, Models, Biological, Obesity, Adipocytes
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