Plasma Exosomes Aggravate Acute Pancreatitis by Promoting M1 Polarization of Adipose Tissue Macrophages in Obesity-Related Severe Acute Pancreatitis

Background and Aims Obesity may be a risk factor for severe acute pancreatitis (SAP). However, its precise mechanism is not yet fully understood.Methods We fed rats with a standard laboratory diet (SLD) and a high-fat diet (HFD). SAP model rats were established by retrograde injection of sodium taurocholate. Serum non-esterified fatty acids (NEFAs), lipase (LPS), and myeloperoxidase (MPO) were measured, as were adipose IL-1, IL-6, IL-10, and TNF-a levels. HE staining was performed to determine the severity of pancreatitis. Serum exosomes were extracted from rats with obesity-related SAP, verified by transmission electron microscopy (TEM) and western blot analysis, and co-cultured with THP-1 cells. Flow cytometry was used to analyze the M1 and M2 phenotypes of macrophages in adipose tissues and THP-1 cells. Q-PCR was used to analyze the levels of IL-1, IL-6, IL-10, and TNF-a in each group of cells.Results The body weight and serum NEFA concentrations of rats in the HFD group were significantly higher than those in the SLD group. Adipose tissue macrophages in the HFD group exhibited a higher percentage of the M1 type than those in the SLD group. The severity of pancreatitis were significantly increased in the HFD + SAP group. Pro-inflammatory macrophages and cytokines were significantly higher in the HFD + SAP group and THP-1 cells co-cultured with serum exosomes extracted from rats with obesity-related SAP.Conclusions Obesity might worsen the severity of pancreatitis by amplifying the immune response and activating M1 polarization in adipose tissue macrophages via serum exosomes in rats of obesity-related SAP.