Abstract
Obesity causes a wide range of metabolic diseases including diabetes, cardiovascular disease, and kidney disease. Thus, plenty of studies have attempted to discover naturally derived compounds displaying anti-obesity effects. In this study, we evaluated the inhibitory effects of morolic acid 3-O-caffeate (MAOC), extracted from Betula schmidtii, on adipogenesis. Treatment of 3T3-L1 cells with MAOC during adipogenesis significantly reduced lipid accumulation and decreased the expression of adiponectin, a marker of mature adipocytes. Moreover, the treatment with MAOC only during the early phase (day 0–2) sufficiently inhibited adipogenesis, comparable with the inhibitory effects observed following MAOC treatment during the whole processes of adipogenesis. In the early phase of adipogenesis, the expression level of Wnt6, which inhibits adipogenesis, increased by MAOC treatment in 3T3-L1 cells. To identify the gene regulatory mechanism, we assessed alterations in histone modifications upon MAOC treatment. Both global and local levels on the Wnt6 promoter region of histone H3 lysine 4 trimethylation, an active transcriptional histone marker, increased markedly by MAOC treatment in 3T3-L1 cells. Our findings identified an epigenetic event associated with inhibition of adipocyte generation by MAOC, suggesting its potential as an efficient therapeutic compound to cure obesity and metabolic diseases.
Highlights
Obesity is caused by the accumulation of excessive amounts of fat in adipose tissues in the body due to an imbalance between food intake and energy use over a prolonged period [1]
Viability of 3T3-L1 Cells Treated with Morolic Acid 3-O-Caffeate
Based onofthe fact preadipocytes that ursolic acid, oleanolic acid, and acid betulinic acid, which have structures adipogenesis
Summary
Obesity is caused by the accumulation of excessive amounts of fat in adipose tissues in the body due to an imbalance between food intake and energy use over a prolonged period [1]. This prolonged overnutrition induces de novo adipocyte differentiation from preadipocytes, which contributes adipose tissue expansion [2]. Betula schmidtii, which belongs to the Betulaceae family, contains diverse bioactive compounds including phenolic derivatives [3] and triterpenoids [4]. Morolic acid 3-O-caffeate (MAOC) is one of oleanane-type triterpenoid derivatives (Figure 1A). It has been reported that diverse oleanane triterpenoids, including oleanolic acid, betulinic acid, and ursolic acid, exhibit anti-obesity effects.
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