Purple corn extract induces long-lasting reprogramming and M2 phenotypic switch of adipose tissue macrophages in obese mice

Background: Obesity is a chronic and systemic infammatory disorder and an important risk factor for the onset of several chronic syndromes. Adipose tissue (AT) plays a crucial role in the development of obesity, promoting the infl‑ tration and accumulation of leukocytes in the tissue and sustaining adipocyte expansion. Anthocyanins exert a broad range of health benefts, but their efect in improving obesity-related infammation in vivo has been poorly character‑ ized. We examined the efects of a purple corn cob extract in the context of AT infammation in a murine diet-induced obesity (DIO) model. Methods: Male C57BL/6J mice were subjected to control diet (CTR+H2O), high fat diet (HF+H2O) or high fat diet plus purple corn extract (HF+RED) for 12 weeks. Blood glucose, AT, and liver gene expression, metabolism, biochem‑ istry, and histology were analysed and fow cytometry was performed on AT leukocytes and Kupfer cells. Results: RED extract intake resulted in lower MCP-1 mediated recruitment and proliferation of macrophages into crown-like structures in the AT. AT macrophages (ATM) of HF+RED group upregulated M2 markers (ArgI, Fizz1, TGFβ), downregulating infammatory mediators (TNF-α, IL-6, IL-1β, COX-2) thanks to the suppression of NF-kB signalling. ATM also increased the expression of iron metabolism-related genes (FABP4, Hmox1, Ferroportin, CD163, TfR1, Ceruloplasmin, FtL1, FtH1) associated with a reduction in iron storage and increased turnover. ATM from HF+RED mice did not respond to LPS treatment ex vivo, confrming the long-lasting efects of the treatment on M2 polarization. Adipocytes of HF+RED group improved lipid metabolism and displayed a lower infammation grade. Liver histology revealed a remarkable reduction of steatosis in the HF+RED group, and Kupfer cell profling displayed a marked switch towards the M2 phenotype. Conclusions: RED extract attenuated AT infammation in vivo, with a long-lasting reprogramming of ATM and adipo‑ cyte profles towards the anti-infammatory phenotype, therefore representing a valuable supplement in the context of obesity-associated disorders.