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Abstract: FR-PO1077

Altered Gene Expression Profile in the Jejuna and Kidneys of Mice on High-Fructose or High-Fat Diet

Session Information

Category: Health Maintenance, Nutrition, and Metabolism

  • 1500 Health Maintenance, Nutrition, and Metabolism

Authors

  • Zahedi, Kamyar A., University of New Mexico Health Sciences Center, Albuquerque, New Mexico, United States
  • Barone, Sharon L., University of New Mexico Health Sciences Center, Albuquerque, New Mexico, United States
  • Brooks, Marybeth, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, United States
  • Argyropoulos, Christos, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, United States
  • Soleimani, Manoocher, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, United States

Group or Team Name

  • Soleimani Lab.
Background

Metabolic syndrome (MetS) is a complex disorder characterized by visceral obesity, hypertension, and insulin resistance. The increased prevalence of MetS correlates with enhanced dietary consumption of refined sugars (i.e. high fructose corn syrup), fat, and salt. To ascertain the molecular pathways critical to the development of MetS (and specifically hypertension), we examined the alterations in the renal and jejunal transcriptomes of mice on high fructose or high fat diet.

Methods

Jejunal and kidney transcriptomes of mice on high fructose or high fat diet for 4 weeks were compared with mice on normal diet. Enrichment analyses were performed to identify the affected biological processes and molecular pathways.

Results

Provision of high fructose or high fat diet led to extensive alterations in gene expression patterns in both jejuna and kidneys. Enrichment analyses identified specific GO-biological process pathways in both groups. Major metabolism-associated pathways specific to carbohydrate and fat metabolism were dominant in jejuna of high fructose and high fat mice, respectively. Similarly, pathways associated with insulin response and reaction to stress were prevalent in both groups. Intriguingly, pathways associated with immune and inflammatory responses (e.g., TNF-a response, cytokine response and production) were detected in both high fructose and high fat groups. The latter pathways were significantly enriched in the jejuna of mice on high fat vs. high fructose diet. Enrichment analysis of kidney RNA-seq data revealed fewer overt derangements in high fat vs. high fructose group, which included significant enrichment in pathways associated with the regulation of inflammatory and stress responses. Comparison of high fat to high fructose enrichment terms in the kidney revealed increased enrichment in alterations associate with salt and sugar absorption, stress, and insulin response pathways.

Conclusion

Our studies demonstrate the induction of gene alterations due to increased consumption fat and fructose. These changes include metabolic alterations as well as derangements in inflammatory and stress responses which can contribute to elevated blood pressure. Increased dietary fat and/or fructose, individually or in tandem, can significantly contribute to the onset of pathologies associated with MetS.

Funding

  • Other NIH Support