Cargando…

Anti-Obesity Effects of Tanshinone I from Salvia miltiorrhiza Bunge in Mice Fed a High-Fat Diet through Inhibition of Early Adipogenesis

Tanshinone I (Tan I) is a diterpenoid isolated from Salvia miltiorrhiza Bunge and exhibits antitumor effects in several cancers. However, the anti-obesity properties of Tan I remain unexplored. Here, we evaluated the anti-obesity effects of Tan I in high-fat-diet (HFD)-induced obese mice and investi...

Descripción completa

Detalles Bibliográficos
Autores principales: Jung, Dae Young, Kim, Ji-Hyun, Jung, Myeong Ho
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281980/
https://www.ncbi.nlm.nih.gov/pubmed/32349456
http://dx.doi.org/10.3390/nu12051242
_version_ 1783544038100566016
author Jung, Dae Young
Kim, Ji-Hyun
Jung, Myeong Ho
author_facet Jung, Dae Young
Kim, Ji-Hyun
Jung, Myeong Ho
author_sort Jung, Dae Young
collection PubMed
description Tanshinone I (Tan I) is a diterpenoid isolated from Salvia miltiorrhiza Bunge and exhibits antitumor effects in several cancers. However, the anti-obesity properties of Tan I remain unexplored. Here, we evaluated the anti-obesity effects of Tan I in high-fat-diet (HFD)-induced obese mice and investigated the underlying molecular mechanisms in 3T3-L1 cells. HFD-induced obese mice were orally administrated Tan I for eight weeks, and body weight, weight gain, hematoxylin and eosin staining and serum biological parameters were examined. The adipogenesis of 3T3-L1 preadipocytes was assessed using Oil Red O staining and measurement of intracellular triglyceride (TG) levels, and mitotic clonal expansion (MCE) and its related signal molecules were analyzed during early adipogenesis of 3T3-L1 cells. The administration of Tan I significantly reduced body weight, weight gain, and white adipocyte size, and improved obesity-induced serum levels of glucose, free fatty acid, total TG, and total cholesterol in vivo in HFD-induced obese mice. Furthermore, Tan I-administered mice demonstrated improvement of glucose metabolism and insulin sensitivity. Treatment with Tan I inhibited the adipogenesis of 3T3-L1 preadipocytes in vitro, with this inhibition mainly occurring at an early phase of adipogenesis through the attenuation of MCE via cell cycle arrest at the G1/S phase transition. Tan I inhibited the phosphorylation of p38, extracellular signal-regulated kinase (ERK), and Akt during the process of MCE, while it stimulated the phosphorylation of AMP-activated protein kinase. Furthermore, Tan I repressed the expression of CCAAT-enhancer-binding protein β (C/EBPβ), histone H3K9 demethylase JMJD2B, and subsequently cell cycle genes. Moreover, Tan I regulated the expression of early adipogenic transcription factors including GATAs and Kruppel-like factor family factors. These results indicate that Tan I prevents HFD-induced obesity via the inhibition of early adipogenesis, and thus improves glucose metabolism and insulin sensitivity. This suggests that Tan I possesses therapeutic potential for the treatment of obesity and obesity-related diseases.
format Online
Article
Text
id pubmed-7281980
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-72819802020-06-15 Anti-Obesity Effects of Tanshinone I from Salvia miltiorrhiza Bunge in Mice Fed a High-Fat Diet through Inhibition of Early Adipogenesis Jung, Dae Young Kim, Ji-Hyun Jung, Myeong Ho Nutrients Article Tanshinone I (Tan I) is a diterpenoid isolated from Salvia miltiorrhiza Bunge and exhibits antitumor effects in several cancers. However, the anti-obesity properties of Tan I remain unexplored. Here, we evaluated the anti-obesity effects of Tan I in high-fat-diet (HFD)-induced obese mice and investigated the underlying molecular mechanisms in 3T3-L1 cells. HFD-induced obese mice were orally administrated Tan I for eight weeks, and body weight, weight gain, hematoxylin and eosin staining and serum biological parameters were examined. The adipogenesis of 3T3-L1 preadipocytes was assessed using Oil Red O staining and measurement of intracellular triglyceride (TG) levels, and mitotic clonal expansion (MCE) and its related signal molecules were analyzed during early adipogenesis of 3T3-L1 cells. The administration of Tan I significantly reduced body weight, weight gain, and white adipocyte size, and improved obesity-induced serum levels of glucose, free fatty acid, total TG, and total cholesterol in vivo in HFD-induced obese mice. Furthermore, Tan I-administered mice demonstrated improvement of glucose metabolism and insulin sensitivity. Treatment with Tan I inhibited the adipogenesis of 3T3-L1 preadipocytes in vitro, with this inhibition mainly occurring at an early phase of adipogenesis through the attenuation of MCE via cell cycle arrest at the G1/S phase transition. Tan I inhibited the phosphorylation of p38, extracellular signal-regulated kinase (ERK), and Akt during the process of MCE, while it stimulated the phosphorylation of AMP-activated protein kinase. Furthermore, Tan I repressed the expression of CCAAT-enhancer-binding protein β (C/EBPβ), histone H3K9 demethylase JMJD2B, and subsequently cell cycle genes. Moreover, Tan I regulated the expression of early adipogenic transcription factors including GATAs and Kruppel-like factor family factors. These results indicate that Tan I prevents HFD-induced obesity via the inhibition of early adipogenesis, and thus improves glucose metabolism and insulin sensitivity. This suggests that Tan I possesses therapeutic potential for the treatment of obesity and obesity-related diseases. MDPI 2020-04-27 /pmc/articles/PMC7281980/ /pubmed/32349456 http://dx.doi.org/10.3390/nu12051242 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Jung, Dae Young
Kim, Ji-Hyun
Jung, Myeong Ho
Anti-Obesity Effects of Tanshinone I from Salvia miltiorrhiza Bunge in Mice Fed a High-Fat Diet through Inhibition of Early Adipogenesis
title Anti-Obesity Effects of Tanshinone I from Salvia miltiorrhiza Bunge in Mice Fed a High-Fat Diet through Inhibition of Early Adipogenesis
title_full Anti-Obesity Effects of Tanshinone I from Salvia miltiorrhiza Bunge in Mice Fed a High-Fat Diet through Inhibition of Early Adipogenesis
title_fullStr Anti-Obesity Effects of Tanshinone I from Salvia miltiorrhiza Bunge in Mice Fed a High-Fat Diet through Inhibition of Early Adipogenesis
title_full_unstemmed Anti-Obesity Effects of Tanshinone I from Salvia miltiorrhiza Bunge in Mice Fed a High-Fat Diet through Inhibition of Early Adipogenesis
title_short Anti-Obesity Effects of Tanshinone I from Salvia miltiorrhiza Bunge in Mice Fed a High-Fat Diet through Inhibition of Early Adipogenesis
title_sort anti-obesity effects of tanshinone i from salvia miltiorrhiza bunge in mice fed a high-fat diet through inhibition of early adipogenesis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281980/
https://www.ncbi.nlm.nih.gov/pubmed/32349456
http://dx.doi.org/10.3390/nu12051242
work_keys_str_mv AT jungdaeyoung antiobesityeffectsoftanshinoneifromsalviamiltiorrhizabungeinmicefedahighfatdietthroughinhibitionofearlyadipogenesis
AT kimjihyun antiobesityeffectsoftanshinoneifromsalviamiltiorrhizabungeinmicefedahighfatdietthroughinhibitionofearlyadipogenesis
AT jungmyeongho antiobesityeffectsoftanshinoneifromsalviamiltiorrhizabungeinmicefedahighfatdietthroughinhibitionofearlyadipogenesis