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

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

Boden, Guenther·2006·Current Diabetes Reports

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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Crossref · 10.1007/s11892-006-0031-x

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  • The actions of proinflammatory stimuli impair control of numerous signalling pathways regulating skeletal muscle insulin signalling, glucose uptake, mitochondrial fuel oxidation and respiration, impacting negatively upon skeletal muscle energy homeostasis.

    “The actions of these stimuli serve to not only further induce tissue expression and secretion of IL-6 and TNFα (via the NFκB pathway, [3, 4]), but impair control of numerous signalling pathways regulating skeletal muscle insulin signalling, glucose uptake, mitochondrial fuel oxidation and respiration that impact negatively upon skeletal muscle energy homeostasis [2, 5–7].”

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Authors
Boden, G.
Affiliations
Temple University Hospital (US)
Corresponding author
Boden, Guenther
Venue
Current Diabetes Reports
Published
2006-05
Volume
6
Issue
3
Pages
177-181
ISSN
  • 1534-4827 (ISSN-L)
  • 1539-0829
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
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 › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
  • Health Sciences › Medicine › Epidemiology › 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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