Macrophage markers in skeletal muscle of obese subjects are elevated and inversely relate to insulin sensitivity. The present study aimed to investigate whether short-term high-fat high-calorie (HFHC) diet already increases macrophage markers and affects glucose metabolism in skeletal muscle of healthy lean subjects. Muscle biopsies were obtained from 24 healthy lean young men before and after a 5-day HFHC-diet. mRNA expression levels of relevant genes in muscle and glucose, insulin, C-peptide and cholesteryl ester transfer protein (CETP) levels in plasma were measured. In addition, we assessed hepatic triacylglycerol (‘triglyceride’) (HTG) content by magnetic resonance spectroscopy and subcutaneous white adipose tissue (sWAT) biopsies were analysed histologically from a subset of subjects (n=8). A 5-day HFHC-diet markedly increased skeletal muscle mRNA expression of the general macrophage markers CD68 (3.7-fold, P<0.01) and CD14 (3.2-fold, P<0.01), as well as the M1 macrophage markers MARCO (11.2-fold, P<0.05), CD11c (1.8-fold, P<0.05) and MRC1 (1.7-fold, P<0.05). This was accompanied by down-regulation of SLC2A4 and GYS1 mRNA expression, and elevated plasma glucose (+4%, P<0.001) and insulin (+55%, P<0.001) levels together with homoeostasis model assessment of insulin resistance (HOMA-IR) (+48%, P<0.001), suggesting development of insulin resistance (IR). Furthermore, the HFHC-diet markedly increased HTG (+118%, P<0.001) and plasma CETP levels (+21%, P<0.001), a marker of liver macrophage content, whereas sWAT macrophage content remained unchanged. In conclusion, short-term HFHC-diet increases expression of macrophage markers in skeletal muscle of healthy men accompanied by reduced markers of insulin signalling and development of IR. Therefore, recruitment of macrophages into muscle may be an early event in development of IR in response to short-term HFHC-feeding.
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Research Article|
September 19 2014
Short-term high-fat diet increases macrophage markers in skeletal muscle accompanied by impaired insulin signalling in healthy male subjects
Mariëtte R. Boon;
Mariëtte R. Boon
1
*Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands
†Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands
Correspondence: Dr Mariëtte R. Boon (email [email protected]).
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Leontine E. H. Bakker;
Leontine E. H. Bakker
1
*Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands
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Mariëlle C. Haks;
Mariëlle C. Haks
‡Department of Human Movement Sciences, Maastricht University, Maastricht, The Netherlands
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Edwin Quinten;
Edwin Quinten
‡Department of Human Movement Sciences, Maastricht University, Maastricht, The Netherlands
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Gert Schaart;
Gert Schaart
§Department of of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands
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Lianne Van Beek;
Lianne Van Beek
†Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands
∥Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
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Yanan Wang;
Yanan Wang
*Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands
†Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands
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Linda Van Schinkel;
Linda Van Schinkel
*Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands
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Vanessa Van Harmelen;
Vanessa Van Harmelen
†Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands
∥Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
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A. Edo Meinders;
A. Edo Meinders
*Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands
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Tom H. M. Ottenhoff;
Tom H. M. Ottenhoff
‡Department of Human Movement Sciences, Maastricht University, Maastricht, The Netherlands
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Ko Willems Van Dijk;
Ko Willems Van Dijk
*Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands
†Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands
∥Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
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Bruno Guigas;
Bruno Guigas
¶Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands
**Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands
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Ingrid M. Jazet;
Ingrid M. Jazet
1
*Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands
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Patrick C. N. Rensen
Patrick C. N. Rensen
1
*Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands
†Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands
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Publisher: Portland Press Ltd
Received:
March 19 2014
Revision Received:
August 15 2014
Accepted:
August 22 2014
Accepted Manuscript online:
August 22 2014
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2015 Biochemical Society
2015
Clin Sci (Lond) (2015) 128 (2): 143–151.
Article history
Received:
March 19 2014
Revision Received:
August 15 2014
Accepted:
August 22 2014
Accepted Manuscript online:
August 22 2014
Citation
Mariëtte R. Boon, Leontine E. H. Bakker, Mariëlle C. Haks, Edwin Quinten, Gert Schaart, Lianne Van Beek, Yanan Wang, Linda Van Schinkel, Vanessa Van Harmelen, A. Edo Meinders, Tom H. M. Ottenhoff, Ko Willems Van Dijk, Bruno Guigas, Ingrid M. Jazet, Patrick C. N. Rensen; Short-term high-fat diet increases macrophage markers in skeletal muscle accompanied by impaired insulin signalling in healthy male subjects. Clin Sci (Lond) 1 January 2015; 128 (2): 143–151. doi: https://doi.org/10.1042/CS20140179
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