There is an interesting supplement available on the market: Cyanidin, usually available as Cyanidin-glycoside. This supplement is thought to contribute to hypertrophy whilst activation downstream of AMPK signalling and inhibition of mTOR signalling. Apparently, hypertrophy is thought to be caused by lipid and glucose shuttling into myocytes. The study then goes in detail about FOXO1 and MURF/1 signalling:
Activation of AMPK inhibits cardiomyocyte hypertrophy by modulating of the FOXO1/MuRF1 signaling pathway in vitro.
AbstractAIM:To examine the inhibitory effects of adenosine monophosphate-activated protein kinase (AMPK) activation on cardiac hypertrophy in vitro and to investigate the underlying molecular mechanisms.
METHODS:Cultured neonatal rat cardiomyocytes were treated with the specific AMPK activator 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) and the specific AMPK antagonist Compound C, and then stimulated with phenylephrine (PE). The Muscle RING finger 1 (MuRF1)-small interfering RNA (siRNA) was transfected into cardiomyocytes using Lipofectamine 2000. The surface area of cultured cardiomyocytes was measured using planimetry. The protein degradation was determined using high performance liquid chromatography (HPLC). The expression of beta-myosin heavy chain (beta-MHC) and MuRF1, as well as the phosphorylation levels of AMPK and Forkhead box O 1 (FOXO1), were separately measured using Western blot or real-time polymerase chain reaction.
RESULTS:Activation of AMPK by AICAR 0.5 mmol/L inhibited PE-induced increase in cardiomyocyte area and beta-MHC protein expression and PE-induced decrease in protein degradation. Furthermore, AMPK activation increased the activity of transcription factor FOXO1 and up-regulated downstream atrogene MuRF1 mRNA and protein expression. Treatment of hypertrophied cardiomyocytes with Compound C 1 micromol/L blunted the effects of AMPK on cardiomyocyte hypertrophy and changes to the FOXO1/MuRF1 pathway. The effects of AICAR on cardiomyocyte hypertrophy were also blocked after MuRF1 was silenced by transfection of cardiomyocytes with MuRF1-siRNA.
CONCLUSION:The present study demonstrates that AMPK activation attenuates cardiomyocyte hypertrophy by modulating the atrophy-related FOXO1/MuRF1 signaling pathway in vitro.
More on mTOR
Cyanidin-3-O-β-glucoside and protocatechuic acid activate AMPK/mTOR/S6K pathway and improve glucose homeostasis in mice
Show moreAuthor links open overlay panelVeenaTalagavadiaPaoloRapisardabFabioGalvanocPiergiuseppePelicciaMarcoGiorgioaHighlights•
C3G and PCA activate AMPK and inhibit mTOR and S6K.
•C3G and PCA upregulate glucose transporters.
•C3G and PCA improve glucose tolerance and insulin sensitivity.
•PCA sources are promising protectors for type-2 diabetes.
•Blood orange juice improves insulin sensitivity.
AbstractAMP-activated protein kinase (AMPK) activation is an established treatment for diabetes. Here the effects of anthocyanin extract from blood orange juice, i.e. cyanidin-3-O-β-glucoside (C3G) and its secondary metabolite protocatechuic acid (PCA), on AMPK signalling in murine hepatic cell line and in the liver of C57BL/6 mice were investigated. Results showed for the first time that C3G and PCA activate AMPK and suppress its downstream kinase mTOR/S6K both in vitro and in vivo systems. Then, C3G and particularly PCA increased expression of glut 1 and glut 4 in the liver and improved glucose tolerance in normal and obese mice. Finally, the consumption of blood orange juice was observed to increase insulin sensitivity in mice. These findings indicate that C3G and PCA are natural AMPK activators and dietary consumption of food sources of C3G and PCA improves glucose homeostasis. Mainly, blood orange juice has beneficial effect for type 2 diabetes.
Does it prove that strength and lean mass gain (health span) is compatible with longevity? Are there any other mechanisms of hypertrophy without mTOR signalling?
