Adipose-Derived exosome from Diet-Induced-Obese mouse attenuates LPS-Induced acute lung injury by inhibiting inflammation and Apoptosis: In vivo and in silico insight.

BACKGROUND

Acute lung injury (ALI) is a severe clinical condition in the intensive care units, and obesity is a high risk of ALI. Paradoxically, obese ALI patients had better prognosis than non-obese patients, and the mechanism remains largely unknown.

METHODS

Mouse models of ALI and diet-induced-obesity (DIO) were used to investigate the effect of exosomes derived from adipose tissue. The adipose-derived exosomes (ADEs) were isolated by ultracentrifugation, and the role of exosomal miRNAs in the ALI was studied.

RESULTS

Compared with ADEs of control mice (C-Exo), ADEs of DIO mice (D-Exo) increased survival rate and mitigated pulmonary lesions of ALI mice. GO and KEGG analyses showed that the target genes of 40 differentially expressed miRNAs between D-Exo and C-Exo were mainly involved with inflammation, apoptosis and cell cycle. Furthermore, the D-Exo treatment significantly decreased Ly6G cell infiltration, down-regulated levels of pro-inflammatory cytokines (IL-6, IL-12, TNF-α, MCP-1) and chemokines (IL-8 and MIP-2), reduced pulmonary apoptosis and arrest at GG phase (P < 0.01). And the protective effects of D-Exo were better than those of C-Exo (P < 0.05). Compared with the C-Exo mice, the levels of miR-16-5p and miR-335-3p in the D-Exo mice were significantly up-regulated (P < 0.05), and the expressions of IKBKB and TNFSF10, respective target of miR-16-5p and miR-335-3p by bioinformatic analysis, were significantly down-regulated in the D-Exo mice (P < 0.05).

CONCLUSIONS

Exosomes derived from adipose tissue of DIO mice are potent to attenuate LPS-induced ALI, which could be contributed by exosome-carried miRNAs. Our data shed light on the interaction between obesity and ALI.