Description

Liver Macrophage Heterogeneity in Health and Metabolic disease

E. Barreby¹, C. Xu¹, X. Li¹, C. Morgantini¹, J. Jager¹, L. Levi¹, A. Sulen¹, ÅL.Dackland², F. Verdegeur^13* and M. Aouadi^1*.

¹KI/AZ Integrated Cardio Metabolic Center, Department of Medicine, Karolinska Institutet, Stockholm, Sweden; ²Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden; ³Department of Molecular Mechanisms of Disease, University of Zurich, Zurich, Switzerland

^*Contributed equally, corresponding authors

Obesity is a major risk factor for the pathogenesis of insulin resistance and Type 2 diabetes, where the immune system plays an important role. Macrophages are essential mediators in these metabolic disorders and contribute significantly to the regulation of adipose tissue, liver homeostasis and metabolism. However, despite their versatile and multiple functions, very little is known about the different phenotypes of macrophages in metabolic tissues and how these might contribute to insulin resistance. In this study, we have characterized macrophage heterogeneity within the liver using single-cell RNA sequencing of isolated macrophages from lean and obese mice. Two distinct subpopulations of liver macrophages were identified using unsupervised cluster analysis with whole genome scale. Specific gene expression signatures were defined using Monocle, with strong unique characters for each individual subpopulation. Furthermore, the gene expression profile of these macrophage sub-populations was regulated by diet-induced obesity. These results have revealed new insight into macrophage heterogeneity in the liver, and could potentially provide new therapeutic targets for insulin resistance and Type 2 diabetes.