BAIBA Attenuates the Expression of Inflammatory Cytokines and Attachment Molecules and ER Stress in HUVECs and THP-1 Cells

Abstract

Objective: -Aminoisobutyric acid (BAIBA), a myokine, is a thymine catabolite that is induced during exercise, leading to browning of white fat, hepatic fatty acid oxidation, and suppression of hepatic lipogenesis. However, the effects of BAIBA on the progression of atherosclerosis remain unclear. Methods: We performed a Western blot analyses to determine various protein expression. ELISAs (enzyme-linked immunosorbent assays), cell adhesion assays, and cell viability assays were also performed on human umbilical vascular endothelial cells (HUVECs) and human monocytes (THP-1 cells). Results: In the current study, we demonstrate that BAIBA suppresses atherosclerotic reactions caused by lipopolysaccharide (LPS) treatment via an AMPK-dependent pathway. Treatment of HUVECs and THP-1 cells with BAIBA inhibited the LPS-induced phosphorylation of nuclear factor-B (NFB) and the secretion of proinflammatory cytokines. In HUVECs, expression of adhesion molecules and LPS-stimulated adhesion of THP-1 cells to the endothelium were significantly decreased after BAIBA treatment. Furthermore, LPS-induced endoplasmic reticulum (ER) stress and cell toxicity were significantly decreased after BAIBA treatment of HUVECs. Notably, all of these proatherosclerotic effects were fully abrogated by treatment with small interfering RNA targeting AMPK. Conclusion: BAIBA ameliorates LPS-induced atherosclerotic reactions via AMPK-mediated suppression of inflammation and ER stress.