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

Autor: Turner MC; School of Sport, Exercise and Health Sciences, National Centre for Sport and Exercise Medicine, Loughborough University, Loughborough, UK.; Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust, Leicester, UK.; Centre for Sport, Exercise and Life Sciences, Research Institute for Health and Wellbeing, Coventry University, Coventry, UK., Rimington RP; School of Sport, Exercise and Health Sciences, National Centre for Sport and Exercise Medicine, Loughborough University, Loughborough, UK., Martin NRW; School of Sport, Exercise and Health Sciences, National Centre for Sport and Exercise Medicine, Loughborough University, Loughborough, UK., Fleming JW; School of Sport, Exercise and Health Sciences, National Centre for Sport and Exercise Medicine, Loughborough University, Loughborough, UK., Capel AJ; School of Sport, Exercise and Health Sciences, National Centre for Sport and Exercise Medicine, Loughborough University, Loughborough, UK., Hodson L; Oxford Center for Diabetes, Endocrinology and Metabolism, Oxford Biomedical Research Centre, Radcliffe Department of Medicine, Churchill Hospital, University of Oxford, Oxford, UK., Lewis MP; School of Sport, Exercise and Health Sciences, National Centre for Sport and Exercise Medicine, Loughborough University, Loughborough, UK.
Jazyk: angličtina
Zdroj: Journal of cellular physiology [J Cell Physiol] 2021 Oct; Vol. 236 (10), pp. 7033-7044. Date of Electronic Publication: 2021 Mar 19.
DOI: 10.1002/jcp.30365
Abstrakt: 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.
(© 2021 The Authors. Journal of Cellular Physiology published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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