Identification and Spatial Visualization of Dysregulated Bile Acid Metabolism in High-Fat Diet-Fed Mice by Mass Spectral Imaging

Qi Zhang; Zhen-Hua Wu; Shan-Shan Zhao; Jing Yang; Lei Chen; Xiao-Yu Wang; Zhan-You Wang; Hui-Xin Liu

doi:10.3389/fnut.2022.858603

Identification and Spatial Visualization of Dysregulated Bile Acid Metabolism in High-Fat Diet-Fed Mice by Mass Spectral Imaging

Front Nutr. 2022 Mar 30:9:858603. doi: 10.3389/fnut.2022.858603. eCollection 2022.

Authors

Qi Zhang^{1

2}, Zhen-Hua Wu^{1

2

3}, Shan-Shan Zhao^{1

2

3}, Jing Yang^{1

2

3}, Lei Chen^{1

2

3}, Xiao-Yu Wang^{1

2

3}, Zhan-You Wang¹, Hui-Xin Liu^{1

2

3}

Affiliations

¹ Health Sciences Institute, China Medical University, Shenyang, China.
² Institute of Life Sciences, China Medical University, Shenyang, China.
³ Liaoning Key Laboratory of Obesity and Glucose/Lipid Associated Metabolic Diseases, China Medical University, Shenyang, China.

Abstract

Changes in overall bile acid (BA) levels and specific BA metabolites are involved in metabolic diseases, gastrointestinal, and liver cancer. BAs have become established as important signaling molecules that enable fine-tuned inter-tissue communication within the enterohepatic circulation. The liver, BAs site of production, displayed physiological and functional zonal differences in the periportal zone versus the centrilobular zone. In addition, BA metabolism shows regional differences in the intestinal tract. However, there is no available method to detect the spatial distribution and molecular profiling of BAs within the enterohepatic circulation. Herein, we demonstrated the application in mass spectrometry imaging (MSI) with a high spatial resolution (3 μm) plus mass accuracy matrix-assisted laser desorption ionization (MALDI) to imaging BAs and N-1-naphthylphthalamic acid (NPA). Our results could clearly determine the zonation patterns and regional difference characteristics of BAs on mouse liver, ileum, and colon tissue sections, and the relative content of BAs based on NPA could also be ascertained. In conclusion, our method promoted the accessibility of spatial localization and quantitative study of BAs on gastrointestinal tissue sections and demonstrated that MALDI-MSI was a valuable tool to investigate and locate several BA molecules in different tissue types leading to a better understanding of the role of BAs behind the gastrointestinal diseases.

Keywords: MALDI; bile acid; enterohepatic circulation; mass spectrometry imaging (MSI); metabolic disease; zonation pattern.