Guanglin Zhang1,2, Qingying Meng1, Montgomery Blencowe1,3, Rahul Agrawal1,2,4, Fernando Gomez-Pinilla1,2,4, Xia Yang1,3,5. 1. Department of Integrative Biology and Physiology, University of California, Los Angeles, 610 Charles E. Young Drive East, Los Angeles, CA, 90095, USA. 2. Department of Neurosurgery, University of California, Los Angeles, Los Angeles, CA, 90095, USA. 3. Molecular, Cellular, and Integrative Physiology Interdepartmental Program, University of California, Los Angeles, 610 Charles E. Young Drive East, Los Angeles, CA, 90095, USA. 4. Brain Injury Research Center, University of California, Los Angeles, Los Angeles, CA, 90095, USA. 5. Institute for Quantitative and Computational Biosciences, University of California, Los Angeles, 610 Charles E. Young Drive East, Los Angeles, CA, 90095, USA.
Abstract
SCOPE: The influence of docosahexaenoic acid (DHA) on cardiometabolic and cognitive phenotypes, and multi-omic alterations in the brain under two metabolic conditions is explored to understand context-specific nutritional effects. METHODS AND RESULTS: Rats are randomly assigned to a DHA-rich or a control chow diet while drinking water or high fructose solution, followed by profiling of metabolic and cognitive phenotypes and the transcriptome and DNA methylome of the hypothalamus and hippocampus. DHA reduces serum triglyceride and improves insulin resistance and memory exclusively in the fructose-consuming rats. In hippocampus, DHA affects genes related to synapse functions in the chow group but immune functions in the fructose group; in hypothalamus, DHA alters immune pathways in the chow group but metabolic pathways in the fructose group. Network modeling reveals context-specific regulators of DHA effects, including Klf4 and Dusp1 for chow condition and Lum, Fn1, and Col1a1 for fructose condition in hippocampus, as well as Cyr61, JunB, Ier2, and Pitx2 under chow condition and Hcar1, Cdh1, and Osr1 under fructose condition in hypothalamus. CONCLUSION: DHA exhibits differential influence on epigenetic loci, genes, pathways, and metabolic and cognitive phenotypes under different dietary contexts, supporting population stratification in DHA studies to achieve precision nutrition.
SCOPE: The influence of docosahexaenoic acid (DHA) on cardiometabolic and cognitive phenotypes, and multi-omic alterations in the brain under two metabolic conditions is explored to understand context-specific nutritional effects. METHODS AND RESULTS: Rats are randomly assigned to a DHA-rich or a control chow diet while drinking water or high fructose solution, followed by profiling of metabolic and cognitive phenotypes and the transcriptome and DNA methylome of the hypothalamus and hippocampus. DHA reduces serum triglyceride and improves insulin resistance and memory exclusively in the fructose-consuming rats. In hippocampus, DHA affects genes related to synapse functions in the chow group but immune functions in the fructose group; in hypothalamus, DHA alters immune pathways in the chow group but metabolic pathways in the fructose group. Network modeling reveals context-specific regulators of DHA effects, including Klf4 and Dusp1 for chow condition and Lum, Fn1, and Col1a1 for fructose condition in hippocampus, as well as Cyr61, JunB, Ier2, and Pitx2 under chow condition and Hcar1, Cdh1, and Osr1 under fructose condition in hypothalamus. CONCLUSION: DHA exhibits differential influence on epigenetic loci, genes, pathways, and metabolic and cognitive phenotypes under different dietary contexts, supporting population stratification in DHA studies to achieve precision nutrition.
Authors: Kenneth A Pelkey; Elizabeth Barksdale; Michael T Craig; Xiaoqing Yuan; Madhav Sukumaran; Geoffrey A Vargish; Robert M Mitchell; Megan S Wyeth; Ronald S Petralia; Ramesh Chittajallu; Rose-Marie Karlsson; Heather A Cameron; Yasunobu Murata; Matthew T Colonnese; Paul F Worley; Chris J McBain Journal: Neuron Date: 2016-05-04 Impact factor: 17.173
Authors: Cecilie Morland; Krister A Andersson; Øyvind P Haugen; Alena Hadzic; Liv Kleppa; Andreas Gille; Johanne E Rinholm; Vuk Palibrk; Elisabeth H Diget; Lauritz H Kennedy; Tomas Stølen; Eivind Hennestad; Olve Moldestad; Yiqing Cai; Maja Puchades; Stefan Offermanns; Koen Vervaeke; Magnar Bjørås; Ulrik Wisløff; Jon Storm-Mathisen; Linda H Bergersen Journal: Nat Commun Date: 2017-05-23 Impact factor: 14.919
Authors: Asmaa S Abdelhamid; Tracey J Brown; Julii S Brainard; Priti Biswas; Gabrielle C Thorpe; Helen J Moore; Katherine Ho Deane; Fai K AlAbdulghafoor; Carolyn D Summerbell; Helen V Worthington; Fujian Song; Lee Hooper Journal: Cochrane Database Syst Rev Date: 2018-07-18