PLoS ONE (Jan 2016)

Anti-Obesity Effects of Spiramycin In Vitro and In Vivo.

  • Mun Ock Kim,
  • Hyung Won Ryu,
  • Ji-Hee Choi,
  • Tae Hyun Son,
  • Sei-Ryang Oh,
  • Hyun-Sun Lee,
  • Heung Joo Yuk,
  • Sungchan Cho,
  • Jong Soon Kang,
  • Chang Woo Lee,
  • Jinhyuk Lee,
  • Chong-Kil Lee,
  • Sung-Tae Hong,
  • Su Ui Lee

DOI
https://doi.org/10.1371/journal.pone.0158632
Journal volume & issue
Vol. 11, no. 7
p. e0158632

Abstract

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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.