Nutrigenomic Effects of a High-Fat Diet and a Dietary Change to a Low-Fat Diet in the Pancreas in a Mouse Model of Pancreatic Carcinogenesis †
Department of Nutrition, University of California, Davis, CA 95616, USA
*
Author to whom correspondence should be addressed.
†
Presented at the 14th European Nutrition Conference FENS 2023, Belgrade, Serbia, 14–17 November 2023.
Proceedings 2023, 91(1), 222; https://doi.org/10.3390/proceedings2023091222
Published: 4 February 2024
(This article belongs to the Proceedings of The 14th European Nutrition Conference FENS 2023)
Abstract
:Pancreatic cancer is one of the deadliest cancers, with a 5 year survival rate of around 10% globally. Although obesity is a modifiable risk factor for this cancer, the role of a high-fat diet (HFD) intake in pancreatic carcinogenesis, the effects of the dietary modification from an HFD to a low-fat diet, and the underlying molecular mechanisms of action are poorly defined. To contribute to understanding these relationships, we assessed the pancreatic global gene expression modulations using an LSL-KrasG12D/+p48Cre/+ (KC) mouse model. Five-week-old mice were fed an HFD (60% energy from fat) or a control diet (11% energy from fat) until 6 months old. In an additional group, the mice consumed an HFD until 3 months old, and then switched to a control diet for 3 months to evaluate the effects of a dietary change to a low-fat diet (DC). Pancreata were collected, RNA was extracted and sequenced, and bioinformatic analysis was performed to identify the biological functions affected by the diets. The HFD significantly modulated the expression of 2166 genes involved in regulating cellular metabolism (metabolic pathways, oxidative phosphorylation, and pancreatic secretion), cancer-specific functions (pathways in cancer and transcriptional misregulation in cancer), immune function (Th17, Th1, and Th2 cell differentiations) and cell signaling (cytokine–cytokine receptor interaction and chemokine signaling). The DC altered the expression of 988 genes more compared to that of the HFD, presenting an expression profile similar to the control diet. The modulated genes were linked with metabolic processes (pancreatic secretion, fat digestion, and absorption), cell signaling (chemokine signaling, NFκB, and TNF signaling pathways), and cancer-specific functions (proteoglycans in cancer and pathways in cancer). Over 800 genes, mainly linked with metabolic functions, were identified following both DC and HFD intake and presented opposing expression profiles, suggesting that a DC could counteract some nutrigenomic modulations prompted by an HFD. Moreover, this effect was mirrored in the pancreas and final body weights, with the DC mitigating the HFD-induced increases in both the parameters. In summary, we showed the multi-target mode of action of an HFD in the pancreas of KC mice accompanied by increases in pancreatic and body weights that were all neutralized by a 3-month-long switch to a low-fat diet. Further explorations of the possible regulators driving the observed multi-genomic effects are warranted.
Author Contributions
Conceptualization, J.W., A.S.E., G.G.M., I.K.; investigation and methodology, I.K., J.W., A.S.E., G.G.M.; validation, J.W., A.S.E. and G.G.M.; formal analysis, I.K., J.W.; writing—original draft preparation, I.K.; writing—review and editing, J.W., A.S.E., G.G.M., I.K.; supervision, G.G.M.; project administration and funding acquisition, J.W., G.G.M. All authors have read and agreed to the published version of the manuscript.
Funding
This research was funded by the Oncology Dietetic Practice Group and Research Dietetic Practice Group of the Academy of Nutrition and Dietetics, University of California Davis and NIFA-USDA (CA-D-NUT-2397-H) to G.G.M.
Institutional Review Board Statement
The animal study protocol was approved by the Animal Care and Use Committee of the University of California (approval no. 22057, 21 January 2021).
Informed Consent Statement
Not applicable.
Data Availability Statement
The RNASeq data that support the findings will be deposited in the NCBI GEO database upon submission for publication of the full original research paper.
Conflicts of Interest
The authors declare no conflict of interest.
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MDPI and ACS Style
Krga, I.; Wirkus, J.; Ead, A.S.; Mackenzie, G.G. Nutrigenomic Effects of a High-Fat Diet and a Dietary Change to a Low-Fat Diet in the Pancreas in a Mouse Model of Pancreatic Carcinogenesis. Proceedings 2023, 91, 222. https://doi.org/10.3390/proceedings2023091222
AMA Style
Krga I, Wirkus J, Ead AS, Mackenzie GG. Nutrigenomic Effects of a High-Fat Diet and a Dietary Change to a Low-Fat Diet in the Pancreas in a Mouse Model of Pancreatic Carcinogenesis. Proceedings. 2023; 91(1):222. https://doi.org/10.3390/proceedings2023091222
Chicago/Turabian StyleKrga, Irena, Joanna Wirkus, Aya Samir Ead, and Gerardo Guillermo Mackenzie. 2023. "Nutrigenomic Effects of a High-Fat Diet and a Dietary Change to a Low-Fat Diet in the Pancreas in a Mouse Model of Pancreatic Carcinogenesis" Proceedings 91, no. 1: 222. https://doi.org/10.3390/proceedings2023091222
