RNA-sequencing revealed apple pomace ameliorates expression of genes in the hypothalamus associated with neurodegeneration in female rats fed a Western diet during adolescence to adulthood

ABSTRACT

Objectives

Apple pomace, a waste byproduct of apple processing, is rich in nutrients (e.g. polyphenols and soluble fiber) with the potential to be neuroprotective. The aim of this study was to employ RNA-sequencing (RNASeq) technology to investigate diet-gene interactions in the hypothalamus of rats after feeding a Western diet calorically substituted with apple pomace.

Methods

Adolescent (age 21–29 days) female Sprague–Dawley rats were randomly assigned (n = 8 rats/group) to consume either a purified standard diet, Western (WE) diet, or Western diet calorically substituted with 10% apple pomace (WE/AP) for 8 weeks. RNA-seq was performed (n = 5 rats/group) to determine global differentially expressed genes in the hypothalamus.

Results

RNA-seq results comparing rats fed WE to WE/AP revealed 15 differentially expressed genes in the hypothalamus. Caloric substitution of WE diet with 10% apple pomace downregulated (q < 0.06) five genes implicated in brain aging and neurodegenerative disorders: synuclein alpha, phospholipase D family member 5, NADH dehydrogenase Fe-S protein 6, choline O-acetyltransferase, and frizzled class receptor 6.

Discussion

Altered gene expression of these five genes suggests that apple pomace ameliorated synthesis of the neurotransmitter, acetylcholine, in rats fed a WE diet. Apple pomace, a rich source of antioxidant polyphenols and soluble fiber, has been shown to reverse nonalcoholic fatty liver disease (NAFLD). Diet-induced NAFLD decreases hepatic de novo synthesis of choline, a precursor to acetylcholine. Based on preclinical evidence, apple pomace has the potential to be a sustainable functional food for maintaining brain function and for reducing the risk of neurodegeneration.

KEYWORDS:

• Apple pomace
• diet-gene interaction
• hypothalamus
• neurodegenerative
• sustainable food
• Western diet

Acknowledgements

We thank Swilled Dog Hard Cider Company (Franklin, WV) for donating the apple pomace used in this study. Nariman Ktil, BS is acknowledged for assisting with sample preparation. We would also like to acknowledge the WVU Genomics Core Facility, Morgantown WV for support provided to help make this publication possible.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

Data available on request from the authors.

Additional information

Funding

This work was supported by Hatch WVA [grant number 1017641] and CTSI [WVA00718] which in turn provides financial support to the Core Facility.

Notes on contributors

Ayad A. Alawadi

Ayad Alawadi, MS, was a Graduate Research Assistant in the Nutritional Biochemistry Laboratory in Human Nutrition and Foods in the Division of Animal and Nutritional Sciences at West Virginia University, Morgantown, WV. This research was the result of his completed MS thesis.

Vagner A. Benedito

Vagner Benedito, PhD, is an Associate Professor of Biochemical Genetics in the Division of Plant and Soil Sciences at West Virginia University, Morgantown, WV. He contributed his expertise and trained students in RNA-seq technology and analysis.

R. Chris Skinner

Roy Chris Skinner, PhD, is a Research Project Manager in the USDA ARS Food Systems Unit, University of Vermont, Burlington, VA. This research was an extension of his PhD thesis research.

Derek C. Warren

Derek Warren, PhD, is an Assistant Professor of Biology in the Division of Natural Sciences and Mathematics, University of Ozarks, Clarksville, AR. He contributed his expertise and trained students in RNA-seq technology.

Casey Showman

Casey Showman, MS, is a Technician in the Division of Animal and Nutritional Sciences at West Virginia University, Morgantown, WV. She conducted the fatty acid analysis and provided a review of the manuscript.

Janet C. Tou

Janet Tou, PhD, is a Professor of Human Nutrition and Foods in the Division of Animal and Nutritional Sciences at West Virginia University, Morgantown, WV. She provided funding and served as thesis advisor to Ayad Alawadi.