1-Deoxysphingolipids, Early Predictors of Type 2 Diabetes, Compromise the Functionality of Skeletal Myoblasts

Duyen Tran; Stephen Myers; Courtney McGowan; Darren Henstridge; Rajaraman Eri; Sabrina Sonda; Vanni Caruso

doi:10.3389/fendo.2021.772925

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1-Deoxysphingolipids, Early Predictors of Type 2 Diabetes, Compromise the Functionality of Skeletal Myoblasts

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1-Deoxysphingolipids, Early Predictors of Type 2 Diabetes, Compromise the Functionality of Skeletal Myoblasts

Duyen Tran, Stephen Myers, Courtney McGowan, Darren Henstridge, Rajaraman Eri, Sabrina Sonda and Vanni Caruso

Frontiers in endocrinology (Lausanne), Vol.12, pp.1-12

24/12/2021

DOI: https://doi.org/10.3389/fendo.2021.772925

PMID: 35002962

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Abstract

Animals

Apoptosis - drug effects

Autophagy - drug effects

Cell Line

Cell Movement - drug effects

Glucose - metabolism

Insulin Resistance - physiology

Mice

Muscle, Skeletal - drug effects

Muscle, Skeletal - metabolism

Myoblasts, Skeletal - drug effects

Myoblasts, Skeletal - metabolism

Sphingolipids - pharmacology

1-deoxysphingolipids

glucose uptake

myoblasts

myoblast differentiation

autophagy

myotubes

type 2 diabetes mellitus

Metabolic dysfunction, dysregulated differentiation, and atrophy of skeletal muscle occur as part of a cluster of abnormalities associated with the development of Type 2 diabetes mellitus (T2DM). Recent interest has turned to the attention of the role of 1-deoxysphingolipids (1-DSL), atypical class of sphingolipids which are found significantly elevated in patients diagnosed with T2DM but also in the asymptomatic population who later develop T2DM. studies demonstrated that 1-DSL have cytotoxic properties and compromise the secretion of insulin from pancreatic beta cells. However, the role of 1-DSL on the functionality of skeletal muscle cells in the pathophysiology of T2DM still remains unclear. This study aimed to investigate whether 1-DSL are cytotoxic and disrupt the cellular processes of skeletal muscle precursors (myoblasts) and differentiated cells (myotubes) by performing a battery of assays including cell viability adenosine triphosphate assay, migration assay, myoblast fusion assay, glucose uptake assay, and immunocytochemistry. Our results demonstrated that 1-DSL significantly reduced the viability of myoblasts in a concentration and time-dependent manner, and induced apoptosis as well as cellular necrosis. Importantly, myoblasts were more sensitive to the cytotoxic effects induced by 1-DSL rather than by saturated fatty acids, such as palmitate, which are critical mediators of skeletal muscle dysfunction in T2DM. Additionally, 1-DSL significantly reduced the migration ability of myoblasts and the differentiation process of myoblasts into myotubes. 1-DSL also triggered autophagy in myoblasts and significantly reduced insulin-stimulated glucose uptake in myotubes. These findings demonstrate that 1-DSL directly compromise the functionality of skeletal muscle cells and suggest that increased levels of 1-DSL observed during the development of T2DM are likely to contribute to the pathophysiology of muscle dysfunction detected in this disease.

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Title: 1-Deoxysphingolipids, Early Predictors of Type 2 Diabetes, Compromise the Functionality of Skeletal Myoblasts
Creators: Duyen Tran - University of Tasmania
Stephen Myers - University of Tasmania
Courtney McGowan - University of Tasmania
Darren Henstridge - University of Tasmania
Rajaraman Eri - University of Tasmania
Sabrina Sonda - University of Tasmania
Vanni Caruso - University of Tasmania
Publication Details: Frontiers in endocrinology (Lausanne), Vol.12, pp.1-12
Publisher: Frontiers Research Foundation
Identifiers: 991013065340502368
Copyright: Copyright © 2021 Tran,Myers,McGowan, Henstridge, Eri, Sonda and Caruso. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Academic Unit: Faculty of Health; Human Sciences
Language: English
Resource Type: Journal article

1-Deoxysphingolipids, Early Predictors of Type 2 Diabetes, Compromise the Functionality of Skeletal Myoblasts

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