Role of lipid-derived mediators in skeletal muscle insulin resistance
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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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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Mitochondrial fatty acid oxidation in obesity
Serra, D., Mera, P., Malandrino, M. I., Mir, J. F., & Herrero, L. (2013) · Antioxidants & Redox Signaling · doi:10.1089/ars.2012.4875 · Cited by 246 · see citing works
Sheng, L., Cho, K. W., Zhou, Y., Shen, H., & Rui, L. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.256677 · Cited by 45 · see citing works
Cho, K. W., Zhou, Y., Sheng, L., & Rui, L. (2011) · Molecular and Cellular Biology · doi:10.1128/mcb.00459-10 · Cited by 42 · see citing works
Lipocalin 13 regulation of glucose and lipid metabolism in obesity
Zhou, Y., & Rui, L. (2013) · Vitamins & Hormones · doi:10.1016/b978-0-12-407766-9.00015-8 · Cited by 28 · see citing works
- 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
- ORCID
- Eckardt, Kristin
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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