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Biochim Biophys Acta Gen Subj. 2017 Nov;1861(11 Pt A):2690-2701. doi: 10.1016/j.bbagen.2017.07.013. Epub 2017 Jul 20.

DBZ is a putative PPARγ agonist that prevents high fat diet-induced obesity, insulin resistance and gut dysbiosis.

Author information

1
Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal University, Beijing 100875, China.
2
Shijingshan Teaching Hospital of Capital Medical University, Beijing Shijingshan Hospital, Beijing, 100043, China.
3
Gene Engineering and Biotechnology Beijing Key Laboratory, College of Life Sciences, Beijing Normal University, Beijing, 100875, China.
4
Key Laboratory of Resource Biology and Biotechnology in Western China, College of Life Sciences, Northwest University, Xi'an, 710069, China. Electronic address: Zhengxh@nwu.edu.cn.
5
Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal University, Beijing 100875, China; Key Laboratory for Cell Proliferation and Regulation Biology of State Education Ministry, College of Life Sciences, Beijing Normal University, Beijing, 100875, China. Electronic address: ygzhai@bnu.edu.cn.

Abstract

BACKGROUND:

The nuclear receptor PPARγ is an effective pharmacological target for some types of metabolic syndrome, including obesity, diabetes, nonalcoholic fatty liver disease, and cardiovascular disease. However, the current PPARγ-targeting thiazolidinedione drugs have undesirable side effects. Danshensu Bingpian Zhi (DBZ), also known as tanshinol borneol ester derived from Salvia miltiorrhiza, is a synthetic derivative of natural compounds used in traditional Chinese medicine for its anti-inflammatory activity.

METHODS:

In vitro, investigations of DBZ using a luciferase reporter assay and molecular docking identified this compound as a novel promising PPARγ agonist. Ten-week-old C57BL/6J mice were fed either a normal chow diet (NCD) or a high-fat diet (HFD). The HFD-fed mice were gavaged daily with either vehicle or DBZ (50mg/kg or 100mg/kg) for 10weeks. The gut microbiota composition was assessed by analyzing the 16S rRNA gene V3+V4 regions via pyrosequencing.

RESULTS:

DBZ is an efficient natural PPARγ agonist that shows lower PPARγ-responsive luciferase reporter activity than thiazolidinediones, has excellent effects on the metabolic phenotype and exhibits no unwanted adverse effects in a HFD-induced obese mouse model. DBZ protects against HFD-induced body weight gain, insulin resistance, hepatic steatosis and inflammation in mice. DBZ not only stimulates brown adipose tissue (BAT) browning and maintains intestinal barrier integrity but also reverses HFD-induced intestinal microbiota dysbiosis.

CONCLUSIONS:

DBZ is a putative PPARγ agonist that prevents HFD-induced obesity-related metabolic syndrome and reverse gut dysbiosis.

GENERAL SIGNIFICANCE:

DBZ may be used as a beneficial probiotic agent to improve HFD-induced obesity-related metabolic syndrome in obese individuals.

KEYWORDS:

Gut microbiota; Insulin resistance; Obesity; PPARγ

PMID:
28736228
DOI:
10.1016/j.bbagen.2017.07.013
[Indexed for MEDLINE]

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