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Liver, muscle, and adipose tissue insulin action is directly related to intrahepatic triglyceride content in obese subjects.
Open accessAbstract
Background & aims Nonalcoholic fatty liver disease is associated with insulin resistance and diabetes. The purpose of this study was to determine the relationship between intrahepatic triglyceride (IHTG) content and insulin action in liver (suppression of glucose production), skeletal muscle (stimulation of glucose uptake), and adipose tissue (suppression of lipolysis) in nondiabetic obese subjects.Methods A euglycemic-hyperinsulinemic clamp procedure and stable isotopically labeled tracer infusions were used to assess insulin action, and magnetic resonance spectroscopy was used to determine IHTG content, in 42 nondiabetic obese subjects (body mass index, 36 +/- 4 kg/m(2)) who had a wide range of IHTG content (1%-46%).Results Hepatic insulin sensitivity, assessed as a function of glucose production rate and plasma insulin concentration, was inversely correlated with IHTG content (r = -0.599; P < .001). The ability of insulin to suppress fatty acid release from adipose tissue and to stimulate glucose uptake by skeletal muscle were also inversely correlated with IHTG content (adipose tissue: r = -0.590, P < .001; skeletal muscle: r = -0.656, P < .001). Multivariate linear regression analyses found that IHTG content was the best predictor of insulin action in liver, skeletal muscle, and adipose tissue, independent of body mass index and percent body fat, and accounted for 34%, 42%, and 44% of the variability in these tissues, respectively (P < .001 for each model).Conclusions These results show that progressive increases in IHTG content are associated with progressive impairment of insulin action in liver, skeletal muscle, and adipose tissue in nondiabetic obese subjects. Therefore, nonalcoholic fatty liver disease should be considered part of a multiorgan system derangement in insulin sensitivity.
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“Interestingly, hepatic lipid accumulation is also a robust predictor of not only hepatic, but also muscle and adipose insulin sensitivity [better than intraabdominal fat, body mass index (BMI), or other obesity measures] (217, 218).”
From The role of mitochondria in the pathogenesis of type 2 diabetes (2010) · cites this paper as [218]
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Design and validation of a histological scoring system for nonalcoholic fatty liver disease†
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Nonalcoholic Fatty Liver Disease
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Nonalcoholic Fatty Liver Disease
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Local and systemic insulin resistance resulting from hepatic activation of IKK-β and NF-κB
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Nonalcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities
Sanyal, A. J., Campbell–Sargent, C., Mirshahi, F., Rizzo, W. B., Contos, M. J., Sterling, R. K., Luketic, V. A., Shiffman, M. L., & Clore, J. N. (2001) · Gastroenterology · doi:10.1053/gast.2001.23256 · Cited by 2,078
Nonalcoholic fatty liver disease
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Self-citationChait, A., & den Hartigh, L. J. (2020) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2020.00022 · Cited by 1,529
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Metadata
- Authors
- Korenblat, K. M., Fabbrini, E., Mohammed, B. S., & Klein, S.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Klein, Samuel
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2008-05
- Volume
- 134
- Issue
- 5
- Pages
- 1369-1375
- ISSN
- 0016-5085 (ISSN-L)
- PMC
- PMC2629391
- OpenAlex
- W2071867050
- Semantic Scholar
- 583ea7ff89ae3ebd20b01708b92228e15c0f7b02
- Cited by
- 592
- References
- 41
- Citations by year
- 2026: 14 · 2025: 20 · 2024: 31 · 2023: 40 · 2022: 36 · 2021: 32 · 2020: 21 · 2019: 27 · 2018: 32 · 2017: 32 · 2016: 32 · 2015: 32 · 2014: 36 · 2013: 38 · 2012: 44
- FWCI
- 30.68
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
- Funders
- National Institutes of Health (DK 37948, DK 56341, RR-00954, RR-00036)
- Topics
- Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Keywords
- intrahepatic triglyceride, insulin resistance, non-alcoholic fatty liver disease, hepatic insulin sensitivity, skeletal muscle glucose uptake, adipose tissue lipolysis, glucose production, obesity
- MeSH terms
- Adipose Tissue, Adult, Energy Metabolism, Female, Humans, Insulin, Insulin Resistance, Liver, Magnetic Resonance Imaging, Male, Magnetic Resonance Spectroscopy, Obesity, Prognosis, Risk Factors, Triglycerides, Glucose Clamp Technique, Biomarkers, Absorptiometry, Photon, Body Mass Index, Muscle, Skeletal
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