Garlic-derived Exosomes-like Nanoparticles Attenuate Inflammation Response In The White Adipose Of High-fat Diet-fed C57BL/6 Mice

Obesity is a common chronic metabolic disease and a major risk factor for metabolic disorders such as non-alcoholic fatty liver disease,hyperlipidemia,atherosclerosis and type2 diabetes.With the improvement of people’s living conditions and change in lifestyles,the prevalence of obesity is increasing,and it has become a public health problem of general concern.During the occurrence and development of obesity,the continuous expansion of adipose tissue cells leads to the chemotaxis and activation of inflammatory cells,which in turn induces insulin resistance,abnormal liver function,and the formation of other metabolic diseases.Daily exposure of humans to nanoparticles from edible plants is inevitable,but whether edible plant-derived nanoparticles are beneficial to our health keeps to be explored.It has been shown that plant-derived exosome-like nanoparticles(ELNs)can act as a new active ingredient to mediate the host cell-to-cell communication and regulate gene expression,thereby affecting the development of human health and disease.In this study,we screened twenty edible plants derived ELNs and found that garlic-derived exosomes-like nanoparticles(GELNs)attenuated the inflammatory response in lipopolysaccharide(LPS)-induced murine RAW264.7 macrophages by decreasing the production of NO,the levels of M1 pro-inflammatory cytokines including TNF-α,IL-1β,IL-6,i NOS,MCP-1,CLCX10,etc.Moreover,GELNs also increased the m RNA levels of M2 anti-inflammatory cytokines,including IL-10,CD206,Arg1,Mgl1 in LPS-treated RAW264.7 macrophages.In addition,administration of GELNs(i.g.once every other day)for continued 4weeks improved insulin resistance,and decreased the fasting blood glucose and the content of serum insulin in high-fat diet(HFD)-fed C57BL/6 mice.Most importantly,data from H&E and immunofluorescence staining revealed that GELNs supplementation prevented the hypertrophy of adipocytes and the accumulation of macrophages in epididymal white adipose tissue(e WAT)of HFD-fed C57BL/6 mice.Meanwhile,administration of GELNs significantly decreased the m RNA levels of M1 pro-inflammatory cytokines including TNF-α,IL-1β,IL-6,i NOS,and MCP-1,and increased the m RNA levels of M2anti-inflammatory cytokines,such as IL-10,CD206,Arg1,and Ym1 in the e WAT of HFD-fed C57BL/6 mice.All these findings suggest that GELNs may be a new active ingredient in garlic,which show an obvious anti-inflammatory activity in vitro and in vivo,promote the macrophages transformation from M1 pro-inflammation phenotype to M2anti-inflammation,and attenuate the inflammation response in the e WAT of HFD-fed mice,which provided new ideas and targets for the prevention and treatment of obesity,insulin resistance and related metabolic complications.