Cited by 276Adipokines, Inflammation, and Metabolic DiseasesDiet, Metabolism, and DiseaseLiver Disease Diagnosis and Treatment

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Fatty acid—induced inflammation and insulin resistance in skeletal muscle and liver

Boden, Guenther·2006·Current Diabetes Reports

DOI 10.1007/s11892-006-0031-x

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Abstract

Plasma free fatty acid (FFA) levels are elevated in obesity. FFA, by causing insulin resistance in muscle, liver, and endothelial cells, contributes to the development of type 2 diabetes mellitus (T2DM), hypertension, dyslipidemia, and nonalcoholic fatty liver disease (NAFLD). The mechanism through which FFA induces insulin resistance involves intramyocellular and intrahepatocellular accumulation of triglycerides and diacylglycerol, activation of several serine/threonine kinases, reduction in tyrosine phosphorylation of the insulin receptor substrate (IRS)-1/2, and impairment of the IRS/phosphatidylinositol 3-kinase pathway of insulin signaling. FFA also produces low-grade inflammation in skeletal muscle and liver through activation of nuclear factor-kappaB, resulting in release of several proinflammatory and proatherogenic cytokines. Thus, elevated FFA levels (due to obesity or to high-fat feeding) cause insulin resistance in skeletal muscle and liver, which contributes to the development of T2DM, and produce low-grade inflammation, which contributes to the development of atherosclerotic vascular diseases and NAFLD.

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Authors: Boden, G.
Affiliations: Temple University Hospital (US)
Corresponding author: Boden, Guenther
Venue: Current Diabetes Reports
Publisher: Springer Science and Business Media LLC
Published: 2006-05
Volume: 6
Issue: 3
Pages: 177-181
ISSN: 1534-4827 (ISSN-L)
1539-0829
DOI: 10.1007/s11892-006-0031-x
OpenAlex: W2162614886
Cited by: 276
References: 42
Citations by year: 2026: 4 · 2025: 9 · 2024: 15 · 2023: 9 · 2022: 12 · 2021: 15 · 2020: 14 · 2019: 11 · 2018: 14 · 2017: 9 · 2016: 8 · 2015: 25 · 2014: 14 · 2013: 18 · 2012: 20
FWCI: 11.81
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Current Diabetes Reports (publishedVersion)
PubMed (publishedVersion)
Funders: National Heart, Lung, and Blood Institute (R01 HL 733267)
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK058895)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
Keywords: free fatty acids, insulin resistance, low-grade inflammation, skeletal muscle, liver, type 2 diabetes, non-alcoholic fatty liver disease, obesity, high-fat feeding, diacylglycerol, triglyceride accumulation, insulin receptor substrate, phosphatidylinositol 3-kinase, NF-κB, inflammatory cytokines, atherosclerosis
MeSH terms: Diabetes Mellitus, Type 2, Fatty Acids, Nonesterified, Humans, Inflammation, Insulin Resistance, Liver, Obesity, Muscle, Skeletal

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Fatty acid—induced inflammation and insulin resistance in skeletal muscle and liver

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