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Casper, a type of transparent mutant-line zebrafish, was generated to overcome the opaque trunk of an adult zebrafish for tumor modeling to realize real-time visualization of transplanted cells in vivo. However, the molecular information at the metabolic level has not received much attention. Herein, a spatially resolved metabolomics method based on an airflow-assisted desorption electrospray ionization–mass spectrometry imaging (AFADESI-MSI) system for whole-body zebrafish was used to investigate small molecules and the distribution of adult casper (Mitfaw2/w2, roya9/a9) and the differences from wild-type zebrafish. Finally, the spatial distribution information of more than 1500 endogenous ions was obtained in positive and negative detection modes, and 186 metabolites belonging to a variety of structural categories were identified or annotated. Compared with wild-type samples, 85 variables, including 37 known metabolites, were screened out. In addition, the disordered metabolic pathways caused by the genetic mutation were excavated, involving downregulation of purine metabolism and arachidonic acid metabolism, upregulation of glycerophospholipid metabolism, and biosynthesis of unsaturated fatty acids. All these results were observed in the most intuitive way through MSI. This study revealed important metabolic characteristics of and perturbation in adult casper zebrafish, and provides indispensable fundamental knowledge for tumor research based on it.

Understanding the renal region-specific metabolic alteration in different animal models of diabetic nephropathy (DN) is critical for uncovering the underlying mechanisms and for developing effective treatments. In the present study, spatially resolved metabolomics based on air flow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI) was used to compare the local metabolic changes in the kidneys of HFD/STZ-induced diabetic rats and db/db mice. As a result, a total of 67 and 59 discriminating metabolites were identified and visualized in the kidneys of the HFD/STZ-induced diabetic rats and db/db mice, respectively. The result showed that there were significant region-specific changes in the glycolysis, TCA cycle, lipid metabolism, carnitine metabolism, choline metabolism, and purine metabolism in both DN models. However, the regional levels of the ten metabolites, including glucose, AMP, eicosenoic acid, eicosapentaenoic acid, Phosphatidylserine (36:1), Phosphatidylserine (36:4), Phosphatidylethanolamine (34:1), Phosphatidylethanolamine (36:4), Phosphatidylcholine (34:2), Phosphatidylinositol (38:5) were changed in reversed directions, indicating significant differences in the local metabolic phenotypes of these two commonly used DN animal models. This study provides comprehensive and in-depth analysis of the differences in the tissue and molecular pathological features in diabetic kidney injury in HFD/STZ-induced diabetic rats and db/db mice.