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EBioMedicine. 2016 May;7:157-66. doi: 10.1016/j.ebiom.2016.04.008. Epub 2016 Apr 13.

Systems Nutrigenomics Reveals Brain Gene Networks Linking Metabolic and Brain Disorders.

Author information

1
Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
2
Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Maxillofacial Biomedical Engineering, School of Dentistry, Kyung Hee University, Seoul 130-701, Korea.
3
Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
4
Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Center for Synthetic & Systems Biology, TNLIST, Tsinghua University, Beijing 100084, China.
5
Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA.
6
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York 10029, USA.
7
Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Neurosurgery, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: fgomezpi@mednet.ucla.edu.
8
Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: xyang123@ucla.edu.

Abstract

Nutrition plays a significant role in the increasing prevalence of metabolic and brain disorders. Here we employ systems nutrigenomics to scrutinize the genomic bases of nutrient-host interaction underlying disease predisposition or therapeutic potential. We conducted transcriptome and epigenome sequencing of hypothalamus (metabolic control) and hippocampus (cognitive processing) from a rodent model of fructose consumption, and identified significant reprogramming of DNA methylation, transcript abundance, alternative splicing, and gene networks governing cell metabolism, cell communication, inflammation, and neuronal signaling. These signals converged with genetic causal risks of metabolic, neurological, and psychiatric disorders revealed in humans. Gene network modeling uncovered the extracellular matrix genes Bgn and Fmod as main orchestrators of the effects of fructose, as validated using two knockout mouse models. We further demonstrate that an omega-3 fatty acid, DHA, reverses the genomic and network perturbations elicited by fructose, providing molecular support for nutritional interventions to counteract diet-induced metabolic and brain disorders. Our integrative approach complementing rodent and human studies supports the applicability of nutrigenomics principles to predict disease susceptibility and to guide personalized medicine.

KEYWORDS:

Brain disorders; Brain networks; DHA; Epigenome; Extracellular matrix; Fructose; Metabolic diseases; Omega-3 fatty acid; Systems nutrigenomics; Transcriptome

PMID:
27322469
PMCID:
PMC4909610
DOI:
10.1016/j.ebiom.2016.04.008
[Indexed for MEDLINE]
Free PMC Article

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