Miho Sawada1, Hiroyasu Yamamoto2, Ayako Ogasahara1, Yuya Tanaka1, Shinji Kihara1. 1. Department of Biomedical Informatics, Division of Health Sciences, Osaka University Graduate School of Medicine, Osaka, Japan. 2. Department of Biomedical Informatics, Division of Health Sciences, Osaka University Graduate School of Medicine, Osaka, Japan. Electronic address: yamamoto@sahs.med.osaka-u.ac.jp.
Abstract
BACKGROUD: Among various myocyte-derived bioactive molecules (myokines), β-aminoisobutyric acid (BAIBA) is a unique myokine that attenuates skeletal muscle insulin resistance and inflammation, increases browning of white adipose tissue, and enhances hepatic fatty acid oxidation, resulting in upregulated energy expenditure of the whole body. In the present study, we investigated the effects of BAIBA on the vascular endothelial cell function. METHODS: The mRNA levels of proinflammatory molecules, antioxidants, and their related transcription regulators were examined by quantitative RT-PCR in BAIBA-treated human aortic or umbilical vein endothelial cells (HAEC or HUVEC, respectively), with or without tumor necrosis factor (TNF)-α stimulation. The protein expression and phosphorylation of AMP-activated protein kinase (AMPK) and endothelial nitric oxide synthase (eNOS) were determined by Western blot analysis. RESULTS: BAIBA pretreatment significantly suppressed the mRNA levels of the adhesion molecules in the TNF-α-stimulated HAEC and HUVEC. BAIBA treatment significantly increased the mRNA levels of antioxidant molecules, catalase, superoxide dismutases, thioredoxin, and gamma-glutamylcysteine ligases, together with mitochondrial biogenesis-related molecules, nuclear respiratory factor 1, and mitochondrial transcription factor A. In addition, BAIBA treatment significantly increased the transcription factors that regulated these genes [i.e., peroxisome proliferator-activated receptor (PPAR)-δ, PPAR-γ, estrogen-related receptor α (ERRα), and peroxisome proliferator-activated receptor gamma coactivator (PGC)-1β]. Adenovirus-mediated PGC-1β overexpression significantly increased the mRNA levels of all antioxidant molecules. The phosphorylation levels of AMPK and eNOS were unaltered by BAIBA. CONCLUSIONS: In vascular endothelial cells, BAIBA had antiatherogenic effects through the PGC-1β-ERRα/PPAR-δ and PPAR-γ pathway. This can explain the beneficial effects of exercise on vascular endothelial function.
BACKGROUD: Among various myocyte-derived bioactive molecules (myokines), β-aminoisobutyric acid (BAIBA) is a unique myokine that attenuates skeletal muscle insulin resistance and inflammation, increases browning of white adipose tissue, and enhances hepatic fatty acid oxidation, resulting in upregulated energy expenditure of the whole body. In the present study, we investigated the effects of BAIBA on the vascular endothelial cell function. METHODS: The mRNA levels of proinflammatory molecules, antioxidants, and their related transcription regulators were examined by quantitative RT-PCR in BAIBA-treated human aortic or umbilical vein endothelial cells (HAEC or HUVEC, respectively), with or without tumor necrosis factor (TNF)-α stimulation. The protein expression and phosphorylation of AMP-activated protein kinase (AMPK) and endothelial nitric oxide synthase (eNOS) were determined by Western blot analysis. RESULTS:BAIBA pretreatment significantly suppressed the mRNA levels of the adhesion molecules in the TNF-α-stimulated HAEC and HUVEC. BAIBA treatment significantly increased the mRNA levels of antioxidant molecules, catalase, superoxide dismutases, thioredoxin, and gamma-glutamylcysteine ligases, together with mitochondrial biogenesis-related molecules, nuclear respiratory factor 1, and mitochondrial transcription factor A. In addition, BAIBA treatment significantly increased the transcription factors that regulated these genes [i.e., peroxisome proliferator-activated receptor (PPAR)-δ, PPAR-γ, estrogen-related receptor α (ERRα), and peroxisome proliferator-activated receptor gamma coactivator (PGC)-1β]. Adenovirus-mediated PGC-1β overexpression significantly increased the mRNA levels of all antioxidant molecules. The phosphorylation levels of AMPK and eNOS were unaltered by BAIBA. CONCLUSIONS: In vascular endothelial cells, BAIBA had antiatherogenic effects through the PGC-1β-ERRα/PPAR-δ and PPAR-γ pathway. This can explain the beneficial effects of exercise on vascular endothelial function.
Authors: Mano R Maurya; Shakti Gupta; Julie Yi-Shuan Li; Nassim E Ajami; Zhen B Chen; John Y-J Shyy; Shu Chien; Shankar Subramaniam Journal: Proc Natl Acad Sci U S A Date: 2021-01-26 Impact factor: 12.779
Authors: Natalia Jarzebska; Arduino A Mangoni; Jens Martens-Lobenhoffer; Stefanie M Bode-Böger; Roman N Rodionov Journal: Int J Mol Sci Date: 2019-09-17 Impact factor: 5.923