Abstract

Angiopoietin‐like protein 4 (ANGPTL4) may regulate lipoprotein lipase‐dependent plasma clearance of triacylglycerol from skeletal muscle during exercise. The aim of this study was to examine the importance of muscle in regulating ANGPTL4 in response to exercise. We sampled muscle biopsies and serum before, immediately after, and 2 h after 45 min of ergometer cycling. Sampling was done before and after a 12‐week training intervention in controls and dysglycemic subjects. Moreover, fat biopsies were taken before and after the training intervention. The regulation of ANGPTL4 was also investigated in several tissues of exercising mice, and in cultured myotubes. ANGPTL4 levels in serum and expression in muscle were highest 2 h after exercise in both groups. Whereas ANGPTL4 was higher in muscle of exercising controls as compared to dysglycemic subjects, the opposite was observed in serum. In exercising mice, Angptl4 mRNA showed both higher basal expression and induction in liver compared to muscle. Angptl4 mRNA was much higher in adipose tissue than muscle and was also induced by exercise. We observed two mRNA isoforms of ANGPTL4 in muscle and fat in humans. Both were induced by exercise in muscle; one isoform was expressed 5‐ to 10‐fold higher than the other. Studies in mice and cultured myotubes showed that both fatty acids and cortisol have the potential to increase ANGPTL4 expression in muscle during exercise. In conclusion, ANGPTL4 is markedly induced in muscle in response to exercise. However, liver and adipose tissue may contribute more than muscle to the exercise‐induced increase in circulating ANGPTL4.

Highlights

  • During the last decade, it has become apparent that skeletal muscle is a major endocrine organ (Pedersen and Febbraio 2012)

  • We provide evidence suggesting that Angiopoietin-like protein 4 (ANGPTL4) from muscle has limited impact on the serum level and show that muscle and adipose tissue contain two identical ANGPTL4 mRNA isoforms

  • We show that acute exercise increases ANGPTL4 mRNA levels in muscle and protein in serum

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Summary

Introduction

It has become apparent that skeletal muscle is a major endocrine organ (Pedersen and Febbraio 2012). Skeletal muscle can synthesize and secrete several hundred proteins (Bortoluzzi et al 2006; Henningsen et al 2010; Norheim et al 2011). Proteins that are expressed, synthesized, released by myofibers, and exert either paracrine or endocrine effects, are classified as “myokines” (Pedersen and Febbraio 2012). ANGPTL4 is a multifunctional signal protein synthesized by most tissues (Grootaert et al 2012). It is involved in regulation of angiogenesis, glucose and lipid metabolism,

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