High fructose and high fat diets have been associated with increased prevalence of metabolic syndrome, yet our understanding of the tissue, cellular, and molecular sensitivities of these two risk diets remains limited. Using single cell RNA sequencing, we examined thousands of individual cells from hypothalamus, liver, adipose, and small intestine from mice fed a high fat diet, a high fructose diet, and a chow diet. We found significant differences between the two diets in terms of the vulnerable tissues, cell types, and molecular pathways: both diets had significant impact on liver hepatocytes; high fructose diet induced stronger gene expression perturbations in hypothalamic neurons; high fat diet had more prominent influence on adipose cell types. We also identified key differences in tissue-tissue and cell-cell interactions between diets. Our results indicate that high fat and high fructose diets engage different tissues, cell types and molecular pathways, and rewire cell-cell networks to promote metabolic syndrome.


D. Arneson: None. S. Majid: None. I. Ahn: None. Z. Kurt: None. G. Diamante: None. G. Zhang: None. F. Gomez-Pinilla: None. X. Yang: None.


National Institutes of Health (R01DK14363)

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