Genetic Control of Fatty Acid β-Oxidation in Chronic Obstructive Pulmonary Disease

摘要: Bioenergetics homeostasis is important for cells to sustain normal functions and defend against injury. The genetic controls of bioenergetics homeostasis, especially lipid metabolism, remain poorly understood in chronic obstructive pulmonary disease (COPD), the third leading cause death world. Additionally, biological function most susceptibility genes identified from genome-wide association studies (GWASs) COPD remains unclear. Here, we aimed address (1) how fatty acid oxidation (FAO), specifically β-oxidation, a key metabolism pathway that provides energy cells, contributes cigarette smoke (CS)-induced COPD; (2) whether-and if so, how-FAM13A (family with sequence similarity 13 member A), well-replicated GWAS gene, modulates FAO pathway. We demonstrated CS induced expression carnitine palmitoyltransferase 1A (CPT1A), mitochondrial enzyme pathway, thereby enhancing FAO. Pharmacological inhibition by etomoxir blunted CS-induced reactive oxygen species accumulation cell lung epithelial cells. FAM13A promoted FAO, possibly interacting activating sirutin 1, increasing CPT1A. Furthermore, was reduced lungs Fam13a-/- mice. Our results suggest FAM13A, shapes cellular metabolic response exposure promoting which may contribute development.