Next Article in Journal
Assessment of Artemisinin Contents in Selected Artemisia Species from Tajikistan (Central Asia)
Next Article in Special Issue
PharmActa: Empowering Patients to Avoid Clinical Significant Drug–Herb Interactions
Previous Article in Journal
Promising Recent Strategies with Potential Clinical Translational Value to Combat Antibacterial Resistant Surge
Previous Article in Special Issue
Current Status and Major Challenges to the Safety and Efficacy Presented by Chinese Herbal Medicine
Article Menu
Issue 1 (March) cover image

Export Article

Open AccessArticle

Guggulsterone Activates Adipocyte Beiging through Direct Effects on 3T3-L1 Adipocytes and Indirect Effects Mediated through RAW264.7 Macrophages

Department of Animal and Dairy Sciences, University of Georgia, Athens, GA 30605, USA
Department of Foods and Nutrition, University of Georgia, Athens, GA 30605, USA
Department of Pharmaceutical Sciences, School of Pharmacy, Philadelphia College of Osteopathic Medicine-GA Campus, Suwanee, GA 30024, USA
Author to whom correspondence should be addressed.
Both authors contributed equally.
Medicines 2019, 6(1), 22;
Received: 19 December 2018 / Revised: 18 January 2019 / Accepted: 27 January 2019 / Published: 31 January 2019
(This article belongs to the Special Issue Safety of Complementary Medicines)
PDF [2485 KB, uploaded 31 January 2019]


Background: Plant-derived phytochemicals have been of emerging interest as anti-obesity compounds due to their apparent effects on promoting reduced lipid accumulation in adipocytes. Despite such promising evidence, little is known about the potential mechanisms behind their anti-obesity effects. The aim of this study is to establish potential anti-obesity effects of the phytochemical guggulsterone (GS). Methods: Mature 3T3-L1 adipocytes were treated with GS, derived from the guggul plant native in northern India, to investigate its effects on mitochondrial biogenesis and adipocyte “beiging.” Further, to explore the relationship between macrophages and adipocytes, 3T3-L1s were treated with conditioned media from GS-treated RAW264.7 macrophages. Markers of mitochondrial biogenesis and beiging were measured by western blot. Results: GS treatment in adipocytes resulted in increased mitochondrial density, biogenesis (PGC1α and PPARγ), and increased markers of a beige adipocyte phenotype (UCP1, TBX1, and β-3AR). This upregulation in mitochondrial expression was accompanied by increases oxygen consumption. In GS-treated macrophages, markers of M2 polarization were elevated (e.g., arginase and IL-10), along with increased catecholamine release into the media. Lastly, 3T3-L1 adipocytes treated with conditioned media from macrophages induced a 167.8% increase in UCP1 expression, suggestive of a role of macrophages in eliciting an anti-adipogenic response to GS. Conclusions: Results from this study provide the first mechanistic understanding of the anti-obesity effects of GS and suggests a role for both direct GS-signaling and indirect stimulation of M2 macrophage polarization in this model. View Full-Text
Keywords: guggulsterone; obesity; 3T3-L1; beige adipocytes; RAW264.7; M2 polarization guggulsterone; obesity; 3T3-L1; beige adipocytes; RAW264.7; M2 polarization

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Share & Cite This Article

MDPI and ACS Style

Miller, C.N.; Samuels, J.S.; Azhar, Y.; Parmar, A.; Shashidharamurthy, R.; Rayalam, S. Guggulsterone Activates Adipocyte Beiging through Direct Effects on 3T3-L1 Adipocytes and Indirect Effects Mediated through RAW264.7 Macrophages. Medicines 2019, 6, 22.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Medicines EISSN 2305-6320 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top