Cited by 40Adipose Tissue and MetabolismMetabolism, Diabetes, and CancerPeroxisome Proliferator-Activated Receptors

Role of lipid-derived mediators in skeletal muscle insulin resistance

Taube, Annika, Eckardt, Kristin, Eckel, Juergen·2009·American Journal of Physiology-Endocrinology and Metabolism

Abstract

Imbalance between nutritional intake and energy expenditure has been described to culminate in obesity, which predisposes to insulin resistance and type 2 diabetes mellitus. In such states of energy oversupply, excess amounts of lipids are available in tissues and circulation. Over the past years, an increasingly important role in development of skeletal muscle (SkM) insulin resistance has been attributed to lipids and impaired fatty acid metabolism. In this review, we reflect the current state of knowledge about the effects of various lipid-derived mediators on SkM insulin sensitivity. Furthermore, potential mechanisms underlying the biogenesis of intramyocellular ectopic lipid stores are discussed. Previously, a pivotal role was attributed to mitochondrial dysfunction. However, results of recent studies have suggested an important role for exercise deficiency, accompanied by decreased expression levels of peroxisome proliferator-activated receptor-γ coactivator-1α and subsequent, incomplete β-oxidation. Additionally, we summarize the implications of increased levels of lipid-derived endocannabinoids (ECs) for metabolic control in peripheral tissue and highlight the benefits of targeting the EC system.

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Registry

Crossref · 10.1152/ajpendo.00241.2009

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184 of 184 references verified0 citation errors · 0 not checkable

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  • Free fatty acids and their metabolites (such as DAG and ceramides) are important contributors to lipid-induced insulin resistance in skeletal muscle.

    “The lipotoxic hypothesis proposes that FAs and their metabolites (such as DAG and ceramides) are important contributors to lipid-induced insulin resistance in SkM.”

    From Mitochondrial fatty acid oxidation in obesity (2013) · cites this paper as [159]

  • These molecules activate proinflammatory and nutrient-sensing pathways that lead to the impairment of insulin action.

    “These molecules activate proinflammatory and nutrient-sensing pathways that lead to the impairment of insulin action ([Fig. 6A](#f6)) [for further information, readers are referred to additional reviews ([144](#B144), [159](#B159))].”

    From Mitochondrial fatty acid oxidation in obesity (2013) · cites this paper as [159]

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Authors
Taube, A., Eckardt, K., & Eckel, J.
Affiliations
  • Deutsches Diabetes-Zentrum e.V. (DE)
  • Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Duesseldorf, Germany
Venue
American Journal of Physiology-Endocrinology and Metabolism
Published
2009-11
Volume
297
Issue
5
Pages
E1004-E1012
ISSN
  • 0193-1849 (ISSN-L)
  • 1522-1555
OpenAlex
W2122611471
Cited by
40
References
184
Citations by year
2024: 2 · 2023: 1 · 2018: 1 · 2017: 2 · 2016: 2 · 2014: 2 · 2013: 5 · 2012: 3
FWCI
0.91
Type
journal article
Language
en
Open access
closed
Locations
  • American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
Keywords
skeletal muscle insulin resistance, endocannabinoids, mitochondrial dysfunction, PGC-1α, fatty acid beta-oxidation, obesity, type 2 diabetes, insulin sensitivity
MeSH terms
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Animals, Heat-Shock Proteins, Humans, Insulin Resistance, Lipids, Mitochondria, Muscle, Obesity, Transcription Factors, Oxidative Stress, Muscle, Skeletal, Endothelial Cells

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