Myostatin decreases with aerobic exercise and associates with insulin resistance.
OBJECTIVE
There is mounting evidence that skeletal muscle produces and secretes biologically active proteins or "myokines" that facilitate metabolic cross talk between organ systems. The increased expression of myostatin, a secreted anabolic inhibitor of muscle growth and development, has been associated with obesity and insulin resistance. Despite these intriguing findings, there have been few studies linking myostatin and insulin resistance.


METHODS
To explore this relationship in more detail, we quantified myostatin protein in muscle and plasma from 10 insulin-resistant, middle-aged (53.1 ± 5.5 yr) men before and after 6 months of moderate aerobic exercise training (1200 kcal·wk−¹ at 40%-55% VO2peak). To establish a cause-effect relationship, we also injected C57/Bl6 male mice with high physiological levels of recombinant myostatin protein.


RESULTS
Myostatin protein levels were shown to decrease in muscle (37%, P = 0.042, n = 10) and matching plasma samples (from 28.7 ng·mL−¹ pretraining to 22.8 ng·mL−¹ posttraining, P = 0.003, n = 9) with aerobic exercise. Furthermore, the strong correlation between plasma myostatin levels and insulin sensitivity (R² = 0.82, P < 0.001, n = 9) suggested a cause-effect relationship that was subsequently confirmed by inducing insulin resistance in myostatin-injected mice. A modest increase (44%) in plasma myostatin levels was also associated with significant reductions in the insulin-stimulated phosphorylation of Akt (Thr308) in both muscle and liver of myostatin-treated animals.


CONCLUSIONS
These findings indicate that both muscle and plasma myostatin protein levels are regulated by aerobic exercise and, furthermore, that myostatin is in the causal pathway of acquired insulin resistance with physical inactivity.
Hittel
Dustin S
DS
Human Performance Laboratory, Faculty of Kinesiology, Roger Jackson Center for Health and Wellness, University of Calgary, Calgary, Alberta, Canada. dhittel@kin.ucalgary.ca
Axelson
Michelle
M
Sarna
Neha
N
Shearer
Jane
J
Huffman
Kim M
KM
Kraus
William E
WE
D000328:Adult; D000818:Animals; D001706:Biopsy; D004797:Enzyme-Linked Immunosorbent Assay; D015444:Exercise / Q000502:physiology*; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism; D055435:Myostatin / Q000097:blood*; D010766:Phosphorylation / Q000502:physiology
C525911:MSTN protein, human; C525912:Mstn protein, mouse; D055435:Myostatin
J Appl Physiol (1985). 2009 Apr;106(4):1079-85
19196913
Nature. 1997 May 1;387(6628):83-90
9139826
Am J Physiol Endocrinol Metab. 2008 May;294(5):E918-27
18334608
Amino Acids. 2009 Jul;37(2):297-308
18661258
J Mol Endocrinol. 2010 Jan;44(1):55-73
19726620
J Appl Physiol (1985). 2004 Jan;96(1):101-6
12972442
Curr Opin Clin Nutr Metab Care. 2004 Jul;7(4):451-7
15192449
PLoS One. 2009;4(3):e4937
19295913
J Clin Invest. 2009 Sep;119(9):2772-86
19726871
Diabetes. 2009 May;58(5):1133-43
19208906
Acta Physiol Scand. 2005 Mar;183(3):299-307
15743390
Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14938-43
9843994
Mol Cell Endocrinol. 2009 Apr 10;302(1):26-32
19356623
J Appl Physiol (1985). 2009 May;106(5):1720-9
19299575
Med Sci Sports Exerc. 2004 Apr;36(4):574-82
15064583
Clin Cancer Res. 2004 Nov 1;10(21):7192-8
15534092
Physiol Genomics. 2006 Oct 11;27(2):114-21
16849634
J Appl Physiol (1985). 2005 Oct;99(4):1613-8
16002776
J Biol Chem. 2000 Dec 22;275(51):40235-43
10976104
J Clin Endocrinol Metab. 2004 Jun;89(6):2724-7
15181048
J Appl Physiol (1985). 2007 Nov;103(5):1744-51
17823296
Biochem Biophys Res Commun. 2005 Nov 11;337(1):248-55
16182246
Am J Physiol Endocrinol Metab. 2005 Jun;288(6):E1110-9
15644458
Proc Natl Acad Sci U S A. 2007 Jan 23;104(4):1348-53
17229845
J Ren Nutr. 2006 Oct;16(4):312-24
17046615
Exp Biol Med (Maywood). 2003 Jun;228(6):706-9
12773702
J Clin Endocrinol Metab. 2006 Apr;91(4):1434-7
16464946
Diabetes. 2009 Jan;58(1):30-8
18835929
J Gerontol A Biol Sci Med Sci. 2009 Sep;64(9):940-8
19483181
Scand J Med Sci Sports. 2011 Apr;21(2):215-23
19903317
Exp Physiol. 2006 Nov;91(6):983-94
16873457
Eur J Clin Invest. 2006 Oct;36(10):713-9
16968467
Med Sci Sports Exerc. 2004 May;36(5):787-93
15126711
Int J Sport Nutr Exerc Metab. 2004 Aug;14(4):461-72
15467103
Oncogene. 2003 Nov 13;22(51):8221-32
14614446
Med Sci Sports Exerc. 2009 May;41(5):1063-71
19346981
Arch Intern Med. 2004 Jan 12;164(1):31-9
14718319
Cell Signal. 2008 Aug;20(8):1452-8
18472397
Dev Biol. 2005 Jul 1;283(1):58-69
15975431