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Upregulation of skeletal muscle PGC-1? through the elevation of cyclic AMP levels by Cyanidin-3-glucoside enhances exercise performance.

ABSTRACT: Regular exercise and physical training enhance physiological capacity and improve metabolic diseases. Skeletal muscles require peroxisome proliferator-activated receptor-gamma coactivator-1? (PGC-1?) in the process of their adaptation to exercise owing to PGC-1?'s ability to regulate mitochondrial biogenesis, angiogenesis, and oxidative metabolism. Cyanidin-3-glucoside (Cy3G) is a natural polyphenol and a nutraceutical factor, which has several beneficial effects on human health. Here, the effect of Cy3G on exercise performance and the underlying mechanisms involved were investigated. ICR mice were given Cy3G (1?mg/kg, orally) everyday and made to perform weight-loaded swimming exercise for 15 days. The endurance of mice orally administered with Cy3G was improved, enabling them to swim longer (time) and while the levels of exercise-induced lactate and fatigue markers (urea nitrogen, creatinine and total ketone bodies) were reduced. Additionally, the expression of lactate metabolism-related genes (lactate dehydrogenase B and monocarboxylate transporter 1) in gastrocnemius and biceps femoris muscles was increased in response to Cy3G-induced PGC-1? upregulation. In vitro, using C2C12 myotubes, Cy3G-induced elevation of intracellular cyclic AMP levels increased PGC-1? expression via the Ca2+/calmodulin-dependent protein kinase kinase pathway. This study demonstrates that Cy3G enhances exercise performance by activating lactate metabolism through skeletal muscle PGC-1? upregulation.

SUBMITTER: Matsukawa T

PROVIDER: S-EPMC5357948 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Upregulation of skeletal muscle PGC-1α through the elevation of cyclic AMP levels by Cyanidin-3-glucoside enhances exercise performance.

Matsukawa Toshiya T Motojima Hideko H Sato Yuki Y Takahashi Shinya S Villareal Myra O MO Isoda Hiroko H

Scientific reports 20170320

Regular exercise and physical training enhance physiological capacity and improve metabolic diseases. Skeletal muscles require peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) in the process of their adaptation to exercise owing to PGC-1α's ability to regulate mitochondrial biogenesis, angiogenesis, and oxidative metabolism. Cyanidin-3-glucoside (Cy3G) is a natural polyphenol and a nutraceutical factor, which has several beneficial effects on human health. Here, the effec ...[more]

PMID: 28317895

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Project description:BackgroundMulti-monocistronic and multi-variate vectors were designed, built, and tested for the improved production of cyanidin 3-O-glucoside (C3G) in Escherichia coli BL21 (DE3). The synthetic bio-parts were designed in such a way that multiple genes can be assembled using the bio-brick system, and expressed under different promoters in a single vector. The vectors harbor compatible cloning sites, so that the genes can be shuffled from one vector to another in a single step, and assembled into a single vector. The two required genes: anthocyanidin synthase (PhANS) from Petunia hybrida, and cyanidin 3-O-glucosyltransferase (At3GT) from Arabidopsis thaliana, were individually cloned under PT7, Ptrc, and PlacUV5 promoters. Both PhANS and At3GT were shuffled back and forth, so as to generate a combinatorial system for C3G production. The constructed systems were further coupled with the genes for UDP-D-glucose synthesis, all cloned in a multi-monocistronic fashion under PT7. Finally, the production of C3G was checked and confirmed using the modified M9 media, and analyzed through various chromatography and spectrometric analyses.ResultsThe engineered strains endowed with newly generated vectors and the genes for C3G biosynthesis and UDP-D-glucose synthesis were fed with 2 mM (+)-catechin and D-glucose for the production of cyanidin, and its subsequent conversion to C3G. One of the engineered strains harboring At3GT and PhANS under Ptrc promoter and UDP-D-glucose biosynthesis genes under PT7 promoter led to the production of ~?439 mg/L of C3G within 36 h of incubation, when the system was exogenously fed with 5% (w/v) D-glucose. This system did not require exogenous supplementation of UDP-D-glucose.ConclusionA synthetic vector system using different promoters has been developed and used for the synthesis of C3G in E. coli BL21 (DE3) by directing the metabolic flux towards the UDP-D-glucose. This system has the potential of generating better strains for the synthesis of valuable natural products.

Dataset Information

Upregulation of skeletal muscle PGC-1? through the elevation of cyclic AMP levels by Cyanidin-3-glucoside enhances exercise performance.

Publications

Upregulation of skeletal muscle PGC-1α through the elevation of cyclic AMP levels by Cyanidin-3-glucoside enhances exercise performance.

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