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Early Life Methyl Donor Supplementation Attenuates Obesity‐Risk
Author(s) -
McKee Sarah E,
Reyes Teresa M
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1149.2
Subject(s) - offspring , weight gain , pregnancy , gestation , obesity , endocrinology , medicine , biology , lactation , physiology , body weight , genetics
Excessive gestational weight gain is defined when women with a normal pre‐pregnancy body mass index gain more weight than recommended during pregnancy. Excessive gestational weight gain (GWG) has a prevalence rate of nearly 50% and it significantly increases the risk for the development of obesity in the offspring. Excessive GWG can be modeled in animals by feeding pregnant dams a high fat diet, leading to increased maternal weight gain and obesity‐promoting phenotypes in the offspring. Using a mouse model of excessive GWG, we have documented in the offspring an increased preference for sucrose and fat, increased expression of genes that underlie reward‐related behaviors, and both global and gene specific decreases in DNA methylation. These changes in reward‐related neural circuitry may contribute to the increased risk for the development of obesity in the offspring by altering the animal's response to highly palatable, energy dense foods. Methyl donor supplementation (MDS) during pregnancy can reverse some of these obesity‐promoting phenotypes in offspring, yet it is unknown whether postnatal MDS can reverse these phenotypes. To determine this, offspring from dams fed either a high fat diet (HFD) or control diet during gestation were fed a methyl donor supplemented diet during early life (3–6 weeks). We find that postnatal MDS significantly decreased body weight in both male and female adult HFD offspring, and does not alter body weights of control diet offspring. Further, postnatal MDS can rescue adult male fat preference and contributes to region specific normalization of global DNA hypomethylation. We also find that MDS can increase motivation to work for palatable reinforcer in adult female offspring. Continued assessment of obesity development, preference for palatable foods, metabolic phenotypes, and expression changes of genes underlying homeostatic and hedonic feeding will elucidate the mechanism by which early postnatal MDS offsets adult obesity risk. Support or Funding Information NIH MH087978, MH100828, MH106330 to TMR and ES019851 to SEM