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.

Effects of various antimicrobial agents on multi-directional differentiation potential of bone marrow-derived mesenchymal stem cells

“…Studies on the effects of this drug on adipogenesis have revealed that spiramycin inhibits adipogenesis both in vivo and in vitro . Spiramycin at con-centrations of 2.5-20 μmol/L inhibited the adipogenic differentiation of 3T3-L1 pre-adipocyte cells in a dose-dependent manner, which was further confirmed in the high-fat diet-induced obese mice model[69]. It is reported in the above study that salinomycin at 10 μmol/L does not affect the osteogenic differentiation potential of human bone marrow-derived MSCs.…”

Anti-Inflammatory Effects of Spiramycin in LPS-Activated RAW 264.7 Macrophages

“…In this study, we confirmed the possibility of applying an old weapon, spiramycin, to various inflammatory diseases, the new enemy. Spiramycin has been shown to exhibit anti-bacterial, anti-viral, and anti-parasitic activities [ 6 , 7 , 8 , 9 , 10 , 11 , 12 ]. However, no study has reported the anti-inflammatory potential of spiramycin in LPS-induced macrophage RAW 264.7 cells.…”

“…Third is the potential of spiramycin as an anti-obesity treatment and cosmeceutical ingredient. Kim et al reported that HFD-induced obese mice administered with spiramycin showed significant reductions in weight gain, serum leptin levels, adipose tissue mass, and liver lipid accumulation, which effectively attenuated high-fat diet (HFD)-induced obesity and hepatic steatosis by inhibiting adipogenesis [ 12 ]. In addition, according to our unreported results, spiramycin has potential as a whitening cosmeceutical ingredient by inhibiting melanin production in B16F10 melanoma cells.…”

“…It has also been reported to exhibit antiviral activity against enterovirus A71 in vitro and in vivo, enabling its safe administration to children [ 11 ]. In regard to drug repurposing, several studies have reported that spiramycin effectively attenuates obesity and hepatic steatosis caused by a high-fat diet (HFD) by inhibiting adipogenesis [ 12 ]. The focus of this study was to investigate the inhibition of inflammatory mediators and cytokines including nitric oxide (NO), interleukin (IL)-6, and IL-1β, which is the anti-inflammatory capability of spiramycin in lipopolysaccharide (LPS)-induced RAW 264.7 macrophage cells.…”

Pharmacological Properties of a Traditional Korean Formula Bojungchiseup-tang on 3T3-L1 Preadipocytes and High-Fat Diet-Induced Obesity Mouse Model

“…3T3-L1 cells are fibroblast-like preadipocytes, which differentiate into adipocytes, and are commonly used to study adipogenesis [35]. Master transcriptional regulators of adipogenesis, including PPARγ, C/EBPα, and SREBP1c, are necessary modulators of target gene expression that are involved in adipocyte differentia-tion at various stages [36]. C/EBPs consists of six different proteins, C/EBPα, C/EBPβ, C/EBPγ, C/EBPδ, C/EBPε, and C/EBPζ, that are widely expressed in numerous tissues and regulate many cellular processes, including cell cycle, inflammation, differentiation, metabolism, and cellular proliferation [37,38].…”