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

J Transl Med. 2019 Jul 23;17(1):237. doi: 10.1186/s12967-019-1972-6.

Abstract

Background: Obesity is a chronic and systemic inflammatory 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 infiltration and accumulation of leukocytes in the tissue and sustaining adipocyte expansion. Anthocyanins exert a broad range of health benefits, but their effect in improving obesity-related inflammation in vivo has been poorly characterized. We examined the effects of a purple corn cob extract in the context of AT inflammation 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, biochemistry, and histology were analysed and flow cytometry was performed on AT leukocytes and Kupffer 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 inflammatory 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, confirming the long-lasting effects of the treatment on M2 polarization. Adipocytes of HF + RED group improved lipid metabolism and displayed a lower inflammation grade. Liver histology revealed a remarkable reduction of steatosis in the HF + RED group, and Kupffer cell profiling displayed a marked switch towards the M2 phenotype.

Conclusions: RED extract attenuated AT inflammation in vivo, with a long-lasting reprogramming of ATM and adipocyte profiles towards the anti-inflammatory phenotype, therefore representing a valuable supplement in the context of obesity-associated disorders.

Keywords: Adipose tissue; Anthocyanins; Inflammation; Obesity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / cytology
  • Adipocytes / drug effects
  • Adipose Tissue / cytology*
  • Alanine Transaminase / metabolism
  • Animals
  • Anthocyanins / chemistry
  • Blood Glucose / analysis
  • Body Weight
  • Cellular Reprogramming*
  • Diet, High-Fat
  • Gene Expression Regulation
  • Glucose Tolerance Test
  • Inflammation
  • Insulin Resistance
  • Lipopolysaccharides
  • Liver / metabolism
  • Macrophages / cytology
  • Macrophages / drug effects*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Obese
  • Obesity
  • Phenotype
  • Plant Extracts / pharmacology*
  • Zea mays / chemistry*

Substances

  • Anthocyanins
  • Blood Glucose
  • Lipopolysaccharides
  • Plant Extracts
  • Alanine Transaminase