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Effects of 23-epi-26-deoxyactein on Adipogenesis in 3T3-L1 Preadipocytes and Diet-Induced Obesity in C57BL/6 Mice

Effects of 23-epi-26-deoxyactein on Adipogenesis in 3T3-L1 Preadipocytes and Diet-Induced Obesity in C57BL/6 Mice

Jingjing Yuan, Qiangqiang Shi, Juan Chen, Jing Lu, Lu Wang, Minghua Qiu, Jian Liu

Phytomedicine. 2020 Jun 5;76:153264.

PMID: 32570112

Abstract:

Background:
The ethanolic extract of Actaea racemosa L. (Cimicifuga racemosa (L.) Nutt.) has recently been reported to ameliorate obesity-related insulin resistance, hyperlipidemia, and fatty liver in rodents. However, it remains unclear which A. racemosa components are responsible for these beneficial effects.
Purpose:
We aimed to examine the anti-obesity potential of 23-epi-26-deoxyactein (DA), which is contained in the ethanolic extracts of A. racemosa.
Study design and methods:
To evaluate the effects of DA on adipogenesis in 3T3-L1 preadipocytes and diet-induced obesity in C57BL/6 mice, in vitro and in vivo tests were performed. For in vitro assessment, we used Oil red O staining that showed lipid accumulation in differentiated 3T3-L1 cells. For in vivo tests, male 5-week-old C57BL/6 mice were fed with low-fat diet (LFD), high-fat diet (HFD), HFD with 10 mg/kg/d luteolin (LU; positive control drug), HFD with 1 mg/kg/d DA, and HFD with 5 mg/kg/d DA for 12 weeks, respectively. Glucose and insulin tolerance tests were performed at week 17. The lipid deposition of adipose tissue and liver was visualized by hematoxylin and eosin staining. Real-time PCR showed mRNA levels of genes involved in adipogenesis, lipogenesis, and lipolysis. AMPK signaling and SIRT1-FOXO1 pathway were assessed by real-time PCR and western blot.
Results:
10 μM DA and 20 μM LU treatments inhibited 3T3-L1 adipogenesis through down-regulating the expression of C/ebpα, C/ebpβ, and Pparγ, which are the critical adipogenic transcription factors. The in vivo results showed that 5 mg/kg/d DA and 10 mg/kg/d LU significantly lowered body weight gain, fat mass, and liver weight in HFD-fed mice. Meanwhile, DA and LU also reduced insulin resistance and serum lipoprotein levels in HFD-fed mice. Mechanistic studies showed that DA and LU promoted adipocyte lipolysis in mice through activating the AMPK signaling and SIRT1-FOXO1 pathway.
Conclusion:
The in vitro results indicate that 10 μM DA suppresses adipogenesis in 3T3-L1 preadipocytes. The in vivo treatment with 5 mg/kg/d DA ameliorates diet-induced obesity in mice, suggesting that DA is a promising natural compound for the treatment of obesity and related metabolic diseases.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP501938018	23-epi-26-Deoxyactein		501938-01-8	Price

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