Abstract
α-Mangostin, isolated from the hulls of Garcinia mangostana L., was found to have in vitro cytotoxicity against 3T3-L1 cells as well as inhibiting fatty acid synthase (FAS, EC 2.3.1.85). Our studies showed that the cytotoxicity of α-mangostin with IC50 value of 20 µM was incomplicated in apoptotic events including increase of cell membrane permeability, nuclear chromatin condensation and mitochondrial membrane potential (ΔΨm) loss. This cytotoxicity was accompanied by the reduction of FAS activity in cells and could be rescued by 50 µM or 100 µM exogenous palmitic acids, which suggested that the apoptosis of 3T3-L1 preadipocytes induced by α-mangostin was via inhibition of FAS. Futhermore, α-mangostin could suppress intracellular lipid accumulation in the differentiating adipocytes and stimulated lipolysis in mature adipocytes, which was also related to its inhibition of FAS. In addition, 3T3-L1 preadipocytes were more susceptible to the cytotoxic effect of α-mangostin than mature adipocytes. Further studies showed that α-mangostin inhibited FAS probably by stronger action on the ketoacyl synthase domain and weaker action on the acetyl/malonyl transferase domain. These findings suggested that α-mangostin might be useful for preventing or treating obesity.
Highlights
Obesity is a complex metabolic disorder, which affects normal functions of the whole body
To identify whether a-mangostin could inhibit the proliferation of 3T3-L1 preadipocytes, the cells were treated with 0–36 mM amangostin and proliferative capability was determined by MTT assay
In order to examine whether the inhibitory effect on 3T3-L1 preadipocytes by a-mangostin was due to it induced apoptotic cell death, several apoptotic events including increase of cell membrane permeability, nuclear chromatin condensation and mitochondrial membrane potential (DYm) loss were tested
Summary
Obesity is a complex metabolic disorder, which affects normal functions of the whole body. Many parts of human body can be served as targets in treating obesity, one of which is aim at fat storage tissue by regulating fat synthesis/lipolysis/adipose differentiation or apoptosis [2]. Fatty acid is an important source of fat synthesis, but excess of their ectopic accumulation in other functional organs will lead to lipotoxicity, fatty liver and insulin resistance or other obesity-related diseases [3]. The de novo synthesis of long chain fatty acids are catalyzed by fatty acid synthase (FAS, EC 2.3.1.85), which has been considered as an anti-obesity target recently. Inhibiting FAS may significantly reduce weight and treat obesity under the dual mechanism [8]
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