Primary defects in lipolysis and insulin action in skeletal muscle cells from type 2 diabetic individuals
Abstract
A decrease in skeletal muscle lipolysis and hormone sensitive-lipase (HSL) expression has been linked to insulin resistance in obesity. The purpose of this study was to identify potential intrinsic defects in lipid turnover and lipolysis in myotubes established from obese and type 2 diabetic subjects. Lipid trafficking and lipolysis were measured by pulse-chase assay with radiolabeled substrates in myotubes from non-obese/non-diabetic (lean), obese/non-diabetic (obese) and obese/diabetic (T2D) subjects. Lipolytic protein content and level of Akt phosphorylation were measured by Western blot. HSL was overexpressed by adenovirus-mediated gene delivery. Myotubes established from obese and T2D subjects had lower lipolysis (-30-40%) when compared to lean, using oleic acid as precursor. Similar observations were also seen for labelled glycerol. Incorporation of oleic acid into diacylglycerol (DAG) and free fatty acid (FFA) level was lower in T2D myotubes, and acetate incorporation into FFA and complex lipids was also lower in obese and/or T2D subjects. Both protein expression of HSL (but not ATGL) and changes in DAG during lipolysis were markedly lower in cells from obese and T2D when compared to lean subjects. Insulin-stimulated glycogen synthesis (-60%) and Akt phosphorylation (-90%) were lower in myotubes from T2D, however, overexpression of HSL in T2D myotubes did not rescue the diabetic phenotype. In conclusion, intrinsic defects in lipolysis and HSL expression co-exist with reduced insulin action in myotubes from obese T2D subjects. Despite reductions in intramyocellular lipolysis and HSL expression, overexpression of HSL did not rescue defects in insulin action in skeletal myotubes from obese T2D subjects.
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HSL and ATGL need to work in concert to regulate lipolysis in skeletal muscle, and their discordant activity are thought to be responsible for dysregulated lipolysis and IR in the skeletal muscle of obese and type II diabetes mellitus (T2DM) individuals.
“HSL and ATGL need to work in concert to regulate lipolysis in skeletal muscle, and their discordant activity are thought to be responsible for dysregulated lipolysis and IR in the skeletal muscle of obese and type II diabetes mellitus (T2DM) individuals.[ 51 ]”
From Pathogenesis of sarcopenia and the relationship with fat mass: descriptive review (2022) · cites this paper as [51]
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- Authors
- Kase, E. T., Feng, Y. Z., Badin, P.-M., Bakke, S. S., Laurens, C., Coue, M., Langin, D., Gaster, M., Thoresen, G. H., Rustan, A. C., & Moro, C.
- Affiliations
- University of Oslo (NO)
- Université Toulouse III - Paul Sabatier (FR)
- Odense University Hospital (DK)
- Oslo University Hospital (NO)
- Corresponding author
- Kase, Eili T.
- Venue
- Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids
- Publisher
- Elsevier BV
- Published
- 2015-09
- Volume
- 1851
- Issue
- 9
- Pages
- 1194-1201
- ISSN
- 1388-1981 (ISSN-L)
- OpenAlex
- W1988825731
- Cited by
- 36
- References
- 34
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 4 · 2022: 5 · 2021: 3 · 2020: 5 · 2019: 4 · 2018: 1 · 2017: 2 · 2016: 6 · 2015: 1
- FWCI
- 1.66
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids (publishedVersion)
- PubMed (publishedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (publishedVersion)
- HAL (submittedVersion)
- Funders
- NBS (Norwegian biochemical society)
- Norwegian Diabetes foundation
- Anders Jahres Foundation
- National Research Agency (ANR-12-JSV1-0010-01)
- Société Francophone du Diabète
- Danish Medical Research Council
- Novo Nordisk Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- insulin resistance, type 2 diabetes, obesity, hormone-sensitive lipase, myotubes, lipid trafficking, diacylglycerol, free fatty acids, oleic acid incorporation, Akt phosphorylation, adipose triglyceride lipase, adenoviral gene transfer
- MeSH terms
- Biological Transport, Carbon Radioisotopes, Sterol Esterase, Diabetes Mellitus, Type 2, Diglycerides, Female, Gene Expression Regulation, Glycerol, Glycogen, Humans, Insulin, Lipolysis, Male, Middle Aged, Obesity, Signal Transduction, Muscle Fibers, Skeletal, Oleic Acid, Proto-Oncogene Proteins c-akt, Primary Cell Culture
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