Abstract
Ergosterol peroxide is a natural compound of the steroid family found in many fungi, and it possesses antioxidant, anti-inflammatory, anticancer and antiviral activities. The anti-obesity activity of several edible and medicinal mushrooms has been reported, but the effect of mushroom-derived ergosterol peroxide on obesity has not been studied. Therefore, we analyzed the effect of ergosterol peroxide on the inhibition of triglyceride synthesis at protein and mRNA levels and differentiation of 3T3-L1 adipocytes. Ergosterol peroxide inhibited lipid droplet synthesis of differentiated 3T3-L1 cells, expression of peroxisome proliferator-activated receptor gamma (PPARγ) and CCAT/enhancer-binding protein alpha (C/EBPα), the major transcription factors of differentiation, and also the expression of sterol regulatory element-binding protein-1c (SREBP-1c), which promotes the activity of PPARγ, resulting in inhibition of differentiation. It further inhibited the expression of fatty acid synthase (FAS), fatty acid translocase (FAT), and acetyl-coenzyme A carboxylase (ACC), which are lipogenic factors. In addition, it inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs) involved in cell proliferation and activation of early differentiation transcription factors in the mitotic clonal expansion (MCE) stage. As a result, ergosterol peroxide significantly inhibited the synthesis of triglycerides and differentiation of 3T3-L1 cells, and is, therefore, a possibile prophylactic and therapeutic agent for obesity and related metabolic diseases.
Highlights
Obesity is one of the most common diseases worldwide [1]
We evaluated the effect of ergosterol peroxide isolated from the medicinal mushroom Ganoderma lucidum on the differentiation and triacylglycerol synthesis of 3T3-L1 cells
Treatment with ergosterol peroxide significantly inhibited the expression of C/EBPα and PPARγ, key factors in the differentiation of pre-adipocytes, at the protein and mRNA levels
Summary
Obesity is one of the most common diseases worldwide [1]. According to the WHO, obesity worldwide has increased by nearly three times since 1975. Because obesity is associated with many diseases including type 2 diabetes, high blood pressure, cancer and stroke [3], its prevention and treatment are very important. Obesity is caused by excessive accumulation of fatty tissue as a result of an imbalance between energy intake and energy consumption. The increase in adipose tissue is caused by an increase in the number of differentiated adipocytes and an increase in the size of adipocytes due to lipid accumulation. Inhibiting the proliferation and differentiation of adipocytes may be an effective method for the prevention or treatment of obesity and related metabolic diseases [4]
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