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Scripta Scientifica Pharmaceutica

IMPACT OF SHORT- AND LONG-TERM EXERCISE TRAINING ON BRANCHED-CHAIN AMINO ACID TURNOVER AND INSULIN SENSITIVITY IN PRE-DIABETIC AND NORMAL WEIGHT HUMANS

Sindre Lee, Frode Norheim, Hanne L. Gulseth, Torgrim M. Langleite, Li Yuchuan, Andreas Aker, Thomas E. Gundersen, Jørgen Jensen, Torgeir Holen, Kåre I. Birkeland, Christian A. Drevon

Abstract

Introduction: Obesity is associated with reduced insulin sensitivity (IS), reduced branched-chain amino acids (BCAA) catabolism, and elevated plasma BCAA. Physical exercise is known to enhance IS and influence BCAA metabolism.

Aim: To investigate the relationship between BCAA metabolism and IS in overweight/dysglycemic (pT2D) and normal weight (control) individuals during short- and long-term exercise.

Materials and Methods: We measured IS by hyper-insulinemic–euglycemic clamp, transcriptomics by mRNA sequencing of skeletal muscle and adipose tissue biopsies, and plasma concentration of BCAA by HPLC in 13 control men and 13 men with pT2D. Samples were obtained at rest, directly after and 2h after a bicycle challenge, before as well as after 12 weeks of combined endurance- and strength-exercise intervention. The effect of BCAA on glucose metabolism was analyzed in cultured human myotubes.

Results: IS was lower in pT2D vs. controls and increased significantly following exercise in both groups. Plasma concentration of BCAA was higher, whereas BCAA catabolism based on pathway analyses was lower in both skeletal muscle and adipose tissue in pT2D vs. control men. Plasma concentration of BCAA did not change on average with exercise, whereas BCAA catabolism based on transcriptomics increased in both skeletal muscle and adipose tissue. The increase in BCAA catabolism was higher in pT2D vs. control men in both tissues. Increased skeletal muscle catabolism predicted increased IS, the decrease in molar sum of circulating BCAA predicted improvement in HOMA-IR, and the increase in adipose tissue BCAA catabolism predicted increased expression of adipose tissue citric acids cycle enzyme mRNA. The addition of BCAA to cultured myotubes reduced the fractional glucose oxidation.

Conclusion: A mechanism involving increased BCAA catabolism in adipose tissue and skeletal muscle, may mediate interactions between exercise, BCAA metabolism and IS.





DOI: http://dx.doi.org/10.14748/ssp.v4i1.3950

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About The Authors

Sindre Lee

Frode Norheim

Hanne L. Gulseth

Torgrim M. Langleite

Li Yuchuan

Andreas Aker

Thomas E. Gundersen

Jørgen Jensen

Torgeir Holen

Kåre I. Birkeland

Christian A. Drevon

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