Seung-Nam Kim1, Dae Hee Kim1, Hyuek Jong Lee2, Joon Seo Lim3, Ju-Hee Lee1, Sung Yun Park1, Young Jun Koh1. 1. College of Korean Medicine, Dongguk University, Goyang, Republic of Korea. 2. Center for Vascular Research, Institute for Basic Science (IBS), Daejeon, Republic of Korea. 3. Clinical Research Center, Asan Medical Center, Seoul, Republic of Korea.
Abstract
OBJECTIVES: Ginsenoside Rg3 (Rg3), a main active component of Panax ginseng, has various therapeutic properties in literatures, and it has been studied for its potential use in obesity control due to its antiadipogenic effects in white adipocytes. However, little is known about its effects on brown adipocytes. METHODS: The mechanisms through which Rg3 inhibits differentiation, adipogenesis, and ER stress-mediated cell death in mouse primary brown adipocytes (MPBAs) are explored. RESULTS: Rg3 significantly induced cytotoxicity in differentiated MPBAs but not in undifferentiated MPBAs. Rg3 treatment downregulated the expression of differentiation and adipogenesis markers and the level of perilipin in MPBAs while upregulating the expression of lipolytic Kruppel-like factor genes. Rg3 also induced lipolysis and efflux of triglycerides from MPBAs and subsequently increased proinflammatory cytokine levels. Notably, Rg3 treatment resulted in elevation of ER stress and proapoptotic markers in MPBAs. CONCLUSIONS: Our results demonstrate that Rg3 is able to selectively exert cytotoxicity in differentiated MPBAs while leaving undifferentiated MPBAs intact, resulting in the induction of ER stress and subsequent cell death in MPBAs via regulation of various genes related to adipocyte differentiation, adipogenesis, lipolysis, and inflammation. These results indicate that further studies on the potential therapeutic applications of Rg3 are warranted.
OBJECTIVES: Ginsenoside Rg3 (Rg3), a main active component of Panax ginseng, has various therapeutic properties in literatures, and it has been studied for its potential use in obesity control due to its antiadipogenic effects in white adipocytes. However, little is known about its effects on brown adipocytes. METHODS: The mechanisms through which Rg3 inhibits differentiation, adipogenesis, and ER stress-mediated cell death in mouse primary brown adipocytes (MPBAs) are explored. RESULTS: Rg3 significantly induced cytotoxicity in differentiated MPBAs but not in undifferentiated MPBAs. Rg3 treatment downregulated the expression of differentiation and adipogenesis markers and the level of perilipin in MPBAs while upregulating the expression of lipolytic Kruppel-like factor genes. Rg3 also induced lipolysis and efflux of triglycerides from MPBAs and subsequently increased proinflammatory cytokine levels. Notably, Rg3 treatment resulted in elevation of ER stress and proapoptotic markers in MPBAs. CONCLUSIONS: Our results demonstrate that Rg3 is able to selectively exert cytotoxicity in differentiated MPBAs while leaving undifferentiated MPBAs intact, resulting in the induction of ER stress and subsequent cell death in MPBAs via regulation of various genes related to adipocyte differentiation, adipogenesis, lipolysis, and inflammation. These results indicate that further studies on the potential therapeutic applications of Rg3 are warranted.
Authors: Anna Ehrlund; Niklas Mejhert; Christel Björk; Robin Andersson; Agné Kulyté; Gaby Åström; Masayoshi Itoh; Hideya Kawaji; Timo Lassmann; Carsten O Daub; Piero Carninci; Alistair R R Forrest; Yoshihide Hayashizaki; Albin Sandelin; Erik Ingelsson; Mikael Rydén; Jurga Laurencikiene; Peter Arner; Erik Arner Journal: Diabetes Date: 2016-11-01 Impact factor: 9.461