Increased fat accumulation in liver may link insulin resistance with subcutaneous abdominal adipocyte enlargement, visceral adiposity, and hypoadiponectinemia in obese individuals.
Open accessAbstract
BACKGROUND: Enlargement of adipocytes from subcutaneous abdominal adipose tissue (SAT), increased intrahepatic lipid content (IHL), intramyocellular lipid content (IMCL), and low circulating adiponectin concentrations are associated with insulin resistance. OBJECTIVE: Because adiponectin increases fat oxidation in skeletal muscle and liver, and the expression of the adiponectin gene in SAT is inversely associated with adipocyte size, we hypothesized that hypoadiponectinemia links hypertrophic obesity with insulin resistance via increased IMCL and IHL. DESIGN: Fifty-three obese Pima Indians with a mean (+/-SD) age of 27 +/- 8 y, body fat of 35 +/- 5%, and normal glucose regulation (normal fasting and 2-h glucose concentration per WHO 1999 criteria) underwent euglycemic-hyperinsulinemic clamp, biopsies of SAT and vastus lateralis muscle, and magnetic resonance imaging of the abdomen. RESULTS: Adipocyte diameter (AD) correlated positively with body fat (P < 0.0001) and IHL (estimated from magnetic resonance imaging intensity of liver; P = 0.047). No association was found between AD and plasma adiponectin or IMCL. Plasma adiponectin negatively correlated with type II IMCL (IIA, P = 0.004; IIX, P = 0.009) or IHL (P = 0.02). In a multivariate analysis, plasma adiponectin, AD, and visceral adipose tissue (VAT) independently predicted IHL. Low insulin-mediated glucose disposal was associated with low plasma adiponectin (P = 0.02) and high IHL (P = 0.0003), SAT (P = 0.02), and VAT (P = 0.04). High IHL was the only predictor of reduced insulin-mediated suppression of hepatic glucose production (P = 0.02) and the only independent predictor of insulin-mediated glucose disposal in a multivariate analysis. CONCLUSIONS: Increased lipid content in the liver may independently link hypoadiponectinemia, hypertrophic obesity, and increased visceral adiposity with peripheral and hepatic insulin resistance.
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Hepatic lipid accumulation is associated with obesity in humans, particularly central (abdominal) in location, and in parallel with low adiponectin levels.
“Although the relative roles of each of these possibilities is incompletely understood, hepatic lipid accumulation is associated with obesity in humans, particularly central (abdominal) in location (214, 215), and in parallel with low adiponectin levels (216).”
From The role of mitochondria in the pathogenesis of type 2 diabetes (2010) · cites this paper as [216]
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- Authors
- Koska, J., Stefan, N., Permana, P. A., Weyer, C., Sonoda, M., Bogardus, C., Smith, S. R., Joanisse, D. R., Funahashi, T., Krakoff, J., & Bunt, J. C.
- Affiliations
- Pennington Biomedical Research Center (US)
- Corresponding author
- Krakoff, Jonathan
- Venue
- The American Journal of Clinical Nutrition
- Publisher
- Elsevier BV
- Published
- 2008-02
- Volume
- 87
- Issue
- 2
- Pages
- 295-302
- ISSN
- 0002-9165 (ISSN-L)
- OpenAlex
- W2158870913
- Cited by
- 129
- References
- 48
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 10 · 2023: 1 · 2022: 8 · 2021: 5 · 2020: 4 · 2019: 7 · 2018: 2 · 2017: 5 · 2016: 4 · 2015: 12 · 2014: 14 · 2013: 10 · 2012: 8
- FWCI
- 8.87
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- American Journal of Clinical Nutrition (publishedVersion, public-domain)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Health and Human Services
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Keywords
- insulin resistance, adiponectin, hypoadiponectinemia, subcutaneous abdominal fat, adipocyte hypertrophy, visceral fat, intrahepatic lipid, intramyocellular lipid, hepatic steatosis, hepatic glucose production, insulin-stimulated glucose disposal, Pima Indians, obesity
- MeSH terms
- Adult, Fatty Liver, Female, Humans, Indians, North American, Insulin Resistance, Magnetic Resonance Imaging, Male, Obesity, Glucose Clamp Technique, Multivariate Analysis, Adipocytes, Intra-Abdominal Fat, Subcutaneous Fat, Abdominal, Adiponectin
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