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

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.