title: Anti-Obesity Effects of Spiramycin In Vitro and In Vivo.
abstract: The effects of spiramycin on adipogenesis and high fat diet (HFD)-induced obesity were investigated. Potential mechanisms contributing to these effects were elucidated. The inhibitory effect of spiramycin on adipocyte differentiation was assessed using 3T3-L1 preadipocyte cells, in which several parameters involved in AMPK signal pathways and lipid metabolism were examined. To further investigate the pharmacological effects of spiramycin in vivo, we examined several obesity-related parameters in HFD-induced obese mice. Spiramycin significantly inhibited preadipocyte differentiation by attenuating intracellular lipid accumulation. Spiramycin also reduced the expression of adipogenic master regulators (PPARγ, C/EBPα, and SREBP1c) and their downstream target genes (FAS, aP2, and GLUT4) in 3T3-L1 cells. In addition, AMPK phosphorylation was increased by spiramycin treatment in 3T3-L1 cells during early differentiation. Notably, HFD-induced obese mice administered spiramycin showed substantial decreases in body weight gain, serum leptin levels, adipose tissue mass, and hepatic lipid accumulation. Moreover, the decreased levels of GPT and GOT in the serum indicated that spiramycin attenuated hepatic injury caused by HFD. Taken together, these results demonstrate for the first time that spiramycin effectively attenuates HFD-induced obesity and hepatic steatosis by inhibiting adipogenesis.
authors.affiliation: Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang, Cheongju, Chungbuk, 28116, Korea.
authors.forename: Mun Ock
authors.initials: MO
authors.lastname: Kim
authors.affiliation: Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang, Cheongju, Chungbuk, 28116, Korea.
authors.forename: Hyung Won
authors.initials: HW
authors.lastname: Ryu
authors.affiliation: Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang, Cheongju, Chungbuk, 28116, Korea.
authors.forename: Ji-Hee
authors.initials: JH
authors.lastname: Choi
authors.affiliation: Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang, Cheongju, Chungbuk, 28116, Korea.|College of Pharmacy, Chungbuk National University, Cheongju 28644, Korea.
authors.forename: Tae Hyun
authors.initials: TH
authors.lastname: Son
authors.affiliation: Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang, Cheongju, Chungbuk, 28116, Korea.
authors.forename: Sei-Ryang
authors.initials: SR
authors.lastname: Oh
authors.affiliation: Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang, Cheongju, Chungbuk, 28116, Korea.
authors.forename: Hyun-Sun
authors.initials: HS
authors.lastname: Lee
authors.affiliation: Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang, Cheongju, Chungbuk, 28116, Korea.
authors.forename: Heung Joo
authors.initials: HJ
authors.lastname: Yuk
authors.affiliation: Anticancer Agent Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang, Cheongju, Chungbuk, 28116, Korea.
authors.forename: Sungchan
authors.initials: S
authors.lastname: Cho
authors.affiliation: Bio-Evaluation Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang, Cheongju, Chungbuk, 28116, Korea.
authors.forename: Jong Soon
authors.initials: JS
authors.lastname: Kang
authors.affiliation: Bio-Evaluation Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang, Cheongju, Chungbuk, 28116, Korea.
authors.forename: Chang Woo
authors.initials: CW
authors.lastname: Lee
authors.affiliation: Korean Bioinformation Center (KOBIC), Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong, Daejeon, 34141, Korea.
authors.forename: Jinhyuk
authors.initials: J
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju 28644, Korea.
authors.forename: Chong-Kil
authors.initials: CK
authors.lastname: Lee
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science & Technology, 291 Daehak-ro, Yuseong, Daejeon, 34141, Korea.
authors.forename: Sung-Tae
authors.initials: ST
authors.lastname: Hong
authors.affiliation: Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang, Cheongju, Chungbuk, 28116, Korea.
authors.forename: Su Ui
authors.initials: SU
authors.lastname: Lee
mesh_terms: D041721:3T3-L1 Cells; D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects; D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology* / Q000627:therapeutic use; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics; D059305:Diet, High-Fat / Q000009:adverse effects; D005786:Gene Expression Regulation / Q000187:drug effects; D050356:Lipid Metabolism / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D047495:PPAR gamma / Q000235:genetics; D015572:Spiramycin / Q000494:pharmacology* / Q000627:therapeutic use; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics
chemical_list: D019440:Anti-Obesity Agents; D022763:CCAAT-Enhancer-Binding Protein-alpha; D047495:PPAR gamma; D051780:Sterol Regulatory Element Binding Protein 1; D015572:Spiramycin; D055372:AMP-Activated Protein Kinases