3,4-Oxo-isopropylidene-shikimic acid promotes adiopkine expression during murine 3T3-L1 fibroblast differentiation into adipocytes

Objective: 3,4-Oxo-isopropylidene-shikimic acid (ISA), a derivative of shikimic acid, has exhibited ameliorative effect on cognitive impairment in experimental animal models of dementia. This study investigated the effect of ISA on lipid accumulation and adipokine secretion during differentiation of 3T3-L1 fibroblasts to adipocytes. Methods: 3T3-L1 cells were cultured and treated with ISA (50–800 μM) from days 3–8. Lipid accumulation and triglyceride content were measured. Gene expression of adipokines (adiponectin, leptin, and resistin), CCAAT/enhancer binding protein (C/EBP) β, C/EBP α and peroxisome proliferator-activated receptor γ (PPAR γ) and PPAR target genes, including adipocyte fatty acid binding protein (aP2) and fatty acid synthase (FAS) were investigated. Results: ISA promoted 3T3-L1 fibroblast differentiation to adipocytes and increased triglyceride content by 26%. On mechanistic levels, ISA increased expressions of C/EBP β, PPAR γ, C/EBP α, aP2 and FAS. Moreover, ISA stimulated expressions of adipokines secreted by adipocytes, including adiponectin, leptin, and resistin. Conclusions: These findings demonstrated that ISA promoted adipogenesis by up-regulating expressions of C/EBP β, PPAR γ, C/EBP α, aP2 and FAS, and also stimulated adipokines during adipocyte differentiation. Further study should clarify the relationship between stimulation of adipokines and cognitive enhancing effect of ISA.