title: Inhibition of Fatty Acid Synthase Reduces Blastocyst Hatching through Regulation of the AKT Pathway in Pigs.
abstract: Fatty acid synthase (FASN) is an enzyme responsible for the de novo synthesis of long-chain fatty acids. During oncogenesis, FASN plays a role in growth and survival rather than acting within the energy storage pathways. Here, the function of FASN during early embryonic development was studied using its specific inhibitor, C75. We found that the presence of the inhibitor reduced blastocyst hatching. FASN inhibition decreased Cpt1 expression, leading to a reduction in mitochondria numbers and ATP content. This inhibition of FASN resulted in the down-regulation of the AKT pathway, thereby triggering apoptosis through the activation of the p53 pathway. Activation of the apoptotic pathway also leads to increased accumulation of reactive oxygen species and autophagy. In addition, the FASN inhibitor impaired cell proliferation, a parameter of blastocyst quality for outgrowth. The level of OCT4, an important factor in embryonic development, decreased after treatment with the FASN inhibitor. These results show that FASN exerts an effect on early embryonic development by regulating both fatty acid oxidation and the AKT pathway in pigs.
authors.affiliation: Department of Animal Sciences, Chungbuk National University, Chungbuk, Cheongju, Republic of Korea.
authors.forename: Jing
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Animal Sciences, Chungbuk National University, Chungbuk, Cheongju, Republic of Korea.
authors.forename: Nam-Hyung
authors.initials: NH
authors.lastname: Kim
authors.affiliation: Department of Animal Sciences, Chungbuk National University, Chungbuk, Cheongju, Republic of Korea.
authors.forename: Xiang-Shun
authors.initials: XS
authors.lastname: Cui
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001755:Blastocyst / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D015536:Down-Regulation; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology; D005455:Fluorescent Antibody Technique; D035683:MicroRNAs / Q000378:metabolism; D018613:Microscopy, Confocal; D051058:Oncogene Protein v-akt / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013552:Swine / Q000196:embryology
chemical_list: D035683:MicroRNAs; D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate; D064429:Fatty Acid Synthases; D051058:Oncogene Protein v-akt