Probing the Acute and Chronic Inflammation in Pcyt2 ETKO Mouse Model of Metabolic Syndrome
CTP: phosphoethanolamine cytidylyltransferase (Pcyt2) catalyzes the rate-limiting step of the Kennedy pathway. Pcyt2 heterozygous knockouts ETKO) suffer from adult onset obesity, liver steatosis, hypertriglyceridemia, and insulin resistance. This thesis project demonstrated that Pcyt2 ETKO obesity increases liver sensitivity to acute inflammation since enhanced LPS induction of hepatic pro-inflammatory cytokine TNFα and suppressed anti-inflammatory cytokine IL-10 genes expression was detected in ETKO mice than wildtype (WT) mice leading to more TNFα damage and less IL-10 protection. ETKO had higher hepatic NF-κBp65 protein level than WT indicating that Pcyt2 ETKO obesity results in chronic hepatic inflammation. Sea buckthorn extract treatment reduced 4 symptoms of metabolic syndrome in Pcyt2 ETKO mice specifically decreased body weight, lowered tissue lipids (and consequently alleviated NAFL) and blood glucose levels.