Characterization of distinct subpopulations of hepatic macrophages in HFD/obese mice

Hidetaka Morinaga, Rafael Mayoral, Jan Heinrichsdorff, Olivia Osborn, Niclas Franck, Nasun Hah, Evelyn Walenta, Gautam Bandyopadhyay, Ariane R. Pessentheiner, Tyler J. Chi, Heekyung Chung, Juliane G. Bogner-Strauss, Ronald M. Evans, Jerrold M. Olefsky, Dayoung Oh

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

The current dogma is that obesity-associated hepatic inflammation is due to increased Kupffer cell (KC) activation. However, recruited hepatic macrophages (RHMs) were recently shown to represent a sizable liver macrophage population in the context of obesity. Therefore, we assessed whether KCs and RHMs, or both, represent the major liver inflammatory cell type in obesity. We used a combination of in vivo macrophage tracking methodologies and adoptive transfer techniques in which KCs and RHMs are differentially labeled with fluorescent markers. With these approaches, the inflammatory phenotype of these distinct macrophage populations was determined under lean and obese conditions. In vivo macrophage tracking revealed an approximately sixfold higher number of RHMs in obese mice than in lean mice, whereas the number of KCs was comparable. In addition, RHMs comprised smaller size and immature, monocyte-derived cells compared with KCs. Furthermore, RHMs from obese mice were more inflamed and expressed higher levels of tumor necrosis factor-a and interleukin-6 than RHMs from lean mice. A comparison of the MCP-1/C-C chemokine receptor type 2 (CCR2) chemokine system between the two cell types showed that the ligand (MCP-1) is more highly expressed in KCs than in RHMs, whereas CCR2 expression is approximately fivefold greater in RHMs. We conclude that KCs can participate in obesity-induced inflammation by causing the recruitment of RHMs, which are distinct from KCs and are not precursors to KCs. These RHMs then enhance the severity of obesity-induced inflammation and hepatic insulin resistance.

Original languageEnglish (US)
Pages (from-to)1120-1130
Number of pages11
JournalDiabetes
Volume64
Issue number4
DOIs
StatePublished - Apr 2015

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Fingerprint Dive into the research topics of 'Characterization of distinct subpopulations of hepatic macrophages in HFD/obese mice'. Together they form a unique fingerprint.

  • Cite this

    Morinaga, H., Mayoral, R., Heinrichsdorff, J., Osborn, O., Franck, N., Hah, N., Walenta, E., Bandyopadhyay, G., Pessentheiner, A. R., Chi, T. J., Chung, H., Bogner-Strauss, J. G., Evans, R. M., Olefsky, J. M., & Oh, D. (2015). Characterization of distinct subpopulations of hepatic macrophages in HFD/obese mice. Diabetes, 64(4), 1120-1130. https://doi.org/10.2337/db14-1238