Physiological and pathophysiological concentrations of fatty acids induce lipid droplet accumulation and impair functional performance of tissue engineered skeletal muscle

Mark C. Turner, Rowan P. Rimington, Neil R.W. Martin, Jacob W. Fleming, Andrew J. Capel, Leanne Hodson, Mark P. Lewis

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Abstract

Fatty acids (FA) exert physiological and pathophysiological effects leading to changes in skeletal muscle metabolism and function, however, in vitro models to investigate these changes are limited. These experiments sought to establish the effects of physiological and pathophysiological concentrations of exogenous FA upon the function of tissue engineered skeletal muscle (TESkM). Cultured initially for 14 days, C2C12 TESkM was exposed to FA-free bovine serum albumin alone or conjugated to a FA mixture (oleic, palmitic, linoleic, and α-linoleic acids [OPLA] [ratio 45:30:24:1%]) at different concentrations (200 or 800 µM) for an additional 4 days. Subsequently, TESkM morphology, functional capacity, gene expression and insulin signaling were analyzed. There was a dose response increase in the number and size of lipid droplets within the TESkM (p <.05). Exposure to exogenous FA increased the messenger RNA expression of genes involved in lipid storage (perilipin 2 [p <.05]) and metabolism (pyruvate dehydrogenase lipoamide kinase isozyme 4 [p <.01]) in a dose dependent manner. TESkM force production was reduced (tetanic and single twitch) (p <.05) and increases in transcription of type I slow twitch fiber isoform, myosin heavy chain 7, were observed when cultured with 200 µM OPLA compared to control (p <.01). Four days of OPLA exposure results in lipid accumulation in TESkM which in turn results in changes in muscle function and metabolism; thus, providing insight ito the functional and mechanistic changes of TESkM in response to exogenous FA.

Original languageEnglish
Pages (from-to)(In-press)
Number of pages12
JournalJournal of Cellular Physiology
Volume(In-press)
Early online date19 Mar 2021
DOIs
Publication statusE-pub ahead of print - 19 Mar 2021

Bibliographical note

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Funder

This study was funded by the NIHR Leicester Biomedical Research Centre. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. Prof. L Hodson is a British Heart Foundation Senior Research Fellow in Basic Science (FS/15/56/31645).

Keywords

  • contraction
  • insulin sensitivity
  • lipids

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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