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In vitro palmitate treatment of myotubes from postmenopausal women leads to ceramide accumulation, inflammation and affected insulin signaling


Abildgaard, J and Henstridge, DC and Pedersen, AT and Langley, KG and Scheele, C and Pedersen, BK and Lindegaard, B, In vitro palmitate treatment of myotubes from postmenopausal women leads to ceramide accumulation, inflammation and affected insulin signaling, PLoS ONE, 9, (7) pp. e101555. ISSN 1932-6203 (2014) [Refereed Article]


Copyright Statement

Copyright 2014 Abildgaard et al. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0)

DOI: doi:10.1371/journal.pone.0101555


Menopause is associated with an increased incidence of insulin resistance and metabolic diseases. In a chronic palmitate treatment model, we investigated the role of skeletal muscle fatty acid exposure in relation to the metabolic deterioration observed with menopause. Human skeletal muscle satellite cells were isolated from premenopausal (n = 6) and postmenopausal (n = 5) women. In an in vitro model, the myotubes were treated with palmitate (300 ÁM) for one-, two- or three days during differentiation. Effects on lipid accumulation, inflammation and insulin signaling were studied. Palmitate treatment led to a 108% (CI 95%: 50%; 267%) increase in intramyocellular ceramide in the myotubes from the postmenopausal women (post-myotubes) compared with a 26% (CI 95%: -57%; 96%) increase in myotubes from the premenopausal women (pre-myotubes), (p < 0.05). Furthermore, post-myotubes had a 22% (CI 95%: 4%; 34%) increase in pJNK (p = 0.04) and a 114% (CI 95%: 50%; 177%) increase in Hsp70 protein expression (p = 0.03) after three days of palmitate treatment, compared with pre-myotubes, in which no increase in either pJNK (-12% (CI 95: -26%; 2%)) or Hsp70 (7% (CI 95: -78%; 91%)) was detected. Furthermore, post-myotubes showed a blunted insulin stimulated phosphorylation of AS160 in response to chronic palmitate treatment compared with pre-myotubes (p = 0.02). The increased intramyocellular ceramide content in the post-myotubes was associated with a significantly higher mRNA expression of Serine Palmitoyltransferase1 (SPT1) after one day of palmitate treatment (p = 0.03) in post-myotubes compared with pre-myotubes. Our findings indicate that post-myotubes are more prone to develop lipid accumulation and defective insulin signaling following chronic saturated fatty acid exposure as compared to pre-myotubes.

Item Details

Item Type:Refereed Article
Keywords:ceramide, heat shock protein 70, insulin, messenger RNA, palmitic acid, serine palmitoyltransferase, serine palmitoyltransferase 1, stress activated protein kinase, unclassified drug, ceramide, heat shock protein 70, insulin, phosphoprotein, adult
Research Division:Biological Sciences
Research Group:Biochemistry and cell biology
Research Field:Cell metabolism
Objective Division:Health
Objective Group:Specific population health (excl. Indigenous health)
Objective Field:Women's and maternal health
UTAS Author:Henstridge, DC (Dr Darren Henstridge)
ID Code:133350
Year Published:2014
Web of Science® Times Cited:13
Deposited By:Health Sciences
Deposited On:2019-06-24
Last Modified:2019-07-10
Downloads:20 View Download Statistics

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