Apple Pomace Favorably Alters Brain Fatty Acid Composition and Gene Expression in the Hypothalamus of Growing Female Sprague-Dawley Rats Fed a Western Diet Ayad A. Alawadi The hypothalamus plays a major role in regulating food-intake and energy-expenditure. Hypothalamic dysfunction implicated in neurodegenerative diseases is characterized by dietinduced neuroinflammation and energy dysregulation. Apple pomace, a waste byproduct of processing, is rich in polyphenols and soluble fibers, has the

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... tential to ameliorate diet-inducing inflammation. The objective of this study was to determine the effects of Western diet and caloric substitution of Western diet with 10% apple pomace on brain fatty acid composition and gene expression related to hypothalamic function and health in growing female rats. Growing female Sprague-Dawley rats (age 22-29 days) were randomly assigned (n=8 rats/group) to consume purified AIN-93G (control), Western diet, or Western calorically substituted with 10% apple pomace (Western/AP) diets for 8 weeks. Brain lipid content and fatty acid profile analysis were measured. Differentially expressed genes were measured in the hypothalamus using RNA-Seq. Results showed Western/AP diet consisted of the highest amount of soluble fibers and polyphenols. Brain oleic acid was highest in rats fed Western/AP diet (p < 0.0005). RNA-seq results comparing the hypothalamus of rats fed Western to Western/AP showed 15 differentially expressed genes, of which 5 genes: phospholipase D family member 5 (PLD5), synuclein alpha (Snca), NADH dehydrogenase (ubiquinone) fe-s protein 6 (Ndufs6), choline O-acetyltransferase (Chat), and frizzled class receptor 6 (Fzd6) were implicated in neurodegenerative diseases. Apple pomace attenuated the upregulation of Snca (q < 0.05), Chat (q < 0.05), and Ndufs6 (q < 0.05) gene expression, as well as downregulated PLD5 (q < 0.06), and Fzd6 (q < 0.05) gene expression. Results suggested apple pomace constitutes reduced neurodegeneration, acetylcholine impairment, and mitochondrial dysfunction through the modulation of brain lipid content and profile. In conclusion, the results provide evidence that caloric substitution of Western diet with apple pomace has the potential to attenuate the pathogenesis of neurodegenerative diseases. Based on pre-clinical evidence, apple pomace has the potential to be a sustainable functional food for brain health. iv