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.Obesity results from a complex set of interactions between genetics and the environment, and links behavior, metabolism and early in life exposure modeling. In the last several decades, a global epidemic of increasing rates of obesity in humans has been well described but relatively poorly understood at a genomic level 1 . Obesity is known to be heritable, with the most recent in a wave of meta-analyses of body mass index (BMI) genomewide association studies (GWAS) estimating that 97 loci account for approximately 2.7% of BMI variation, and common variants account for up to 21% of BMI variation 2 . However, these loci only nominally predict obesity (defined as BMI ≥ 30 kg per m 2 ), as measured by an improved area under the receiver-operating characteristic curve from 0.576 to 0.601 in a model including age, sex, and four genotype-based principal components 2 . Similarly, GWAS meta-analysis focused on the waist-to-hip ratio (WHR) as a measure of body fat distribution identified 20 loci with female sexual dimorphism which were associated with WHR adjusted for BMI 3 . Notably, these loci generally mapped to genes expressed in mesenchymal derived tissues that are linked to fat distribution and central obesity. These studies are consistent with prior equally robust GWAS analyses, alongside family, twin and adoption studies, and collectively suggest that a wide range (e.g., 40-70%) of inter-individual variability in BMI may be attributed to genetic factors, with FTO and near-MC4R loci seeming to affect obesity-susceptibility