Backgroud: Among various myocyte-derived bioactive molecules (myokines), beta-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)-alpha 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-alpha-stimulated HAEC and HUVEC. BAIBA treatment significantly increased the mRNA levels of antioxidant molecules, catalase, superoxide dismutases, thioredoxin, and gamma-glutamylcysteine ligases, together with mitochondria! 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)-delta, PPAR-gamma, estrogen related receptor alpha (ERR alpha), and peroxisome proliferator-activated receptor gamma coactivator (PGC)-1 beta] Adenovirus-mediated PGC-1 beta 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-1 beta-ERR alpha/PPAR-delta and PPAR-gamma pathway. This can explain the beneficial effects of exercise on vascular endothelial function. (C) 2019 Elsevier Inc. All rights reserved.