Anti-Obesity Effects of Spiramycin In Vitro and In Vivo

PLoS One. 2016 Jul 11;11(7):e0158632. doi: 10.1371/journal.pone.0158632. eCollection 2016.

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.

MeSH terms

  • 3T3-L1 Cells
  • AMP-Activated Protein Kinases / metabolism
  • Adipogenesis / drug effects
  • Animals
  • Anti-Obesity Agents / pharmacology*
  • Anti-Obesity Agents / therapeutic use
  • CCAAT-Enhancer-Binding Protein-alpha / genetics
  • Diet, High-Fat / adverse effects
  • Gene Expression Regulation / drug effects
  • Lipid Metabolism / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Obesity / drug therapy*
  • Obesity / etiology
  • Obesity / metabolism
  • Obesity / pathology
  • PPAR gamma / genetics
  • Spiramycin / pharmacology*
  • Spiramycin / therapeutic use
  • Sterol Regulatory Element Binding Protein 1 / genetics

Substances

  • Anti-Obesity Agents
  • CCAAT-Enhancer-Binding Protein-alpha
  • PPAR gamma
  • Sterol Regulatory Element Binding Protein 1
  • Spiramycin
  • AMP-Activated Protein Kinases

Grants and funding

This work was supported by grants from the Korea Research Institute of Bioscience and Biotechnology Research Initiative Program (KGM1221622) and the Basic Science Research Program of the National Research Foundation (NRF) funded by the Ministry of Science, ICT and Future Planning (NRF-2013R1A1A3008189 and 2013R1A1A3009382). This research was also supported by an NRF of Korea Grant funded by the Korean Government (35B-2011-1-C00033). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.