Genomic Variants Associated with Resistance to High Fat Diet Induced Obesity in a Primate Model

R. Alan Harris, Callison E. Alcott, Elinor Sullivan, Diana Takahashi, Carrie E. McCurdy, Sarah Comstock, Karalee Baquero, Peter Blundell, Antonio Frias, Maike Kahr, Melissa Suter, Stephanie Wesolowski, Jacob E. Friedman, Kevin Grove, Kjersti M. Aagaard

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Maternal obesity contributes to an increased risk of lifelong morbidity and mortality for both the mother and her offspring. In order to better understand the molecular mechanisms underlying these risks, we previously established and extensively characterized a primate model in Macaca fuscata (Japanese macaque). In prior studies we have demonstrated that a high fat, caloric dense maternal diet structures the offspring's epigenome, metabolome, and intestinal microbiome. During the course of this work we have consistently observed that a 36% fat diet leads to obesity in the majority, but not all, of exposed dams. In the current study, we sought to identify the genomic loci rendering resistance to obesity despite chronic consumption of a high fat diet in macaque dams. Through extensive phenotyping together with exon capture array and targeted resequencing, we identified three novel single nucleotide polymorphisms (SNPs), two in apolipoprotein B (APOB) and one in phospholipase A2 (PLA2G4A) that significantly associated with persistent weight stability and insulin sensitivity in lean macaques. By application of explicit orthogonal modeling (NOIA), we estimated the polygenic and interactive nature of these loci against multiple metabolic traits and their measures (i.e., serum LDL levels) which collectively render an obesity resistant phenotype in our adult female dams.

Original languageEnglish (US)
Article number36123
JournalScientific Reports
Volume6
DOIs
StatePublished - Nov 4 2016

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Macaca
High Fat Diet
Primates
Obesity
Fats
Mothers
Diet
Metabolome
Phospholipases A2
Apolipoproteins B
Single Nucleotide Polymorphism
Insulin Resistance
Exons
Morbidity
Phenotype
Weights and Measures
Mortality
Serum

ASJC Scopus subject areas

  • General

Cite this

Harris, R. A., Alcott, C. E., Sullivan, E., Takahashi, D., McCurdy, C. E., Comstock, S., ... Aagaard, K. M. (2016). Genomic Variants Associated with Resistance to High Fat Diet Induced Obesity in a Primate Model. Scientific Reports, 6, [36123]. https://doi.org/10.1038/srep36123

Genomic Variants Associated with Resistance to High Fat Diet Induced Obesity in a Primate Model. / Harris, R. Alan; Alcott, Callison E.; Sullivan, Elinor; Takahashi, Diana; McCurdy, Carrie E.; Comstock, Sarah; Baquero, Karalee; Blundell, Peter; Frias, Antonio; Kahr, Maike; Suter, Melissa; Wesolowski, Stephanie; Friedman, Jacob E.; Grove, Kevin; Aagaard, Kjersti M.

In: Scientific Reports, Vol. 6, 36123, 04.11.2016.

Research output: Contribution to journalArticle

Harris, RA, Alcott, CE, Sullivan, E, Takahashi, D, McCurdy, CE, Comstock, S, Baquero, K, Blundell, P, Frias, A, Kahr, M, Suter, M, Wesolowski, S, Friedman, JE, Grove, K & Aagaard, KM 2016, 'Genomic Variants Associated with Resistance to High Fat Diet Induced Obesity in a Primate Model', Scientific Reports, vol. 6, 36123. https://doi.org/10.1038/srep36123
Harris, R. Alan ; Alcott, Callison E. ; Sullivan, Elinor ; Takahashi, Diana ; McCurdy, Carrie E. ; Comstock, Sarah ; Baquero, Karalee ; Blundell, Peter ; Frias, Antonio ; Kahr, Maike ; Suter, Melissa ; Wesolowski, Stephanie ; Friedman, Jacob E. ; Grove, Kevin ; Aagaard, Kjersti M. / Genomic Variants Associated with Resistance to High Fat Diet Induced Obesity in a Primate Model. In: Scientific Reports. 2016 ; Vol. 6.
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