Cited by 592Liver Disease Diagnosis and TreatmentDiabetes, Cardiovascular Risks, and LipoproteinsDiet, Metabolism, and Disease

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Liver, muscle, and adipose tissue insulin action is directly related to intrahepatic triglyceride content in obese subjects.

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Korenblat, Kevin M., Fabbrini, Elisa, Mohammed, B. Selma, Klein, Samuel·2008·Gastroenterology

DOI 10.1053/j.gastro.2008.01.075PMC PMC2629391

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Abstract

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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Authors: Korenblat, K. M., Fabbrini, E., Mohammed, B. S., & Klein, S.
Affiliations: Washington University in St. Louis (US)
Corresponding author: Klein, Samuel
ORCID: Korenblat, Kevin M.
Fabbrini, Elisa
Klein, Samuel
Venue: Gastroenterology
Publisher: Elsevier BV
Published: 2008-05
Volume: 134
Issue: 5
Pages: 1369-1375
ISSN: 0016-5085 (ISSN-L)
DOI: 10.1053/j.gastro.2008.01.075
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
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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Liver, muscle, and adipose tissue insulin action is directly related to intrahepatic triglyceride content in obese subjects.

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