Young adult mice exposed to postnatal neglect display downregulation of transcription factors in visceral white adipose tissue

Abstract

Exposure to early life stress or adverse childhood experiences is associated with a greater BMI and cardio‐metabolic disease risk. We have previously shown that maternal separation and early weaning (MSEW), a model of early life stress and neglect, exacerbates adipose tissue expansion and metabolic dysfunction during obesity‐induced hypertension in adult female MSEW mice compared with males. Thus, the goal of this study was to determine whether there are sex‐specific changes in fat mass and glucose homeostasis in juvenile and young adult male and female mice exposed to MSEW. We also investigated the status of adipose tissue transcription factors. MSEW was performed by separating the pups from the mother for periods of 4 to 8 hour during postnatal days 2–16. Mice were weaned at postnatal day 17 (P17). Control mice remained undisturbed in the home cage at all times and were weaned at P21. We used 4 control and 4 MSEW li‐‐‐‐tters. All observations were averaged within litters by sex, and analysis was performed with litters as experimental units. Body weight (BW) and fat mass measured by EcoMRI were similar between control and MSEW mice at P17, P21 and P56 when fed a regular chow in both sexes. At P60, one subset of littermates was placed on a low fat diet (LF, 10% kcal from fat) for one week. LF‐fed MSEW and control mice showed similar BW and fat mass; however, the number of pre‐adipocytes isolated from Gonadal white adipose tissue (gWAT) stromal vascular fraction were increased significantly in MSEW mice (p<0.05). The other subset of littermates was placed one week on a high fat diet (HF, 60% kcal from fat). MSEW increased BW and fat mass in HF‐fed mice. Six‐hour fasting glucose was higher in mice exposed to MSEW regardless sex or diet, although the oral glucose tolerance test was not different between groups. Further, gWAT was isolated in mice after one week of LF or HF, and mRNA was isolated for nanoString analysis of transcription factors (nanoString Technologies, Inc, Seattle, WA). We found that one week of HF significantly downregulated: Foxo1 (−1.24±0.07 fold), Sirt1 (−1.51±0.24 fold), Stat5a (−1.53±0.16 fold), Foxp2 (−3.02±0.96 fold), and IL‐6 (−2.74±0.55 fold) compared with controls (p<0.05). Overall, the effect of MSEW on fat mass and glucose metabolism is independent of sex and diet in weanlings and young adults. Downregulation of transcription factors such as Sirt1 could promote lipogenesis by reducing lipolysis. Our study suggests that a chronic HF feeding is required for greater fat expansion and cardio‐metabolic dysfunction in adult female mice.Support or Funding InformationThis study was supported by funds from the NIH National Heart, Lung, and Blood Institute to A.S.L (R00 HL111354), start‐up funds from the University of Kentucky to A.S.L, and the pilot project from the University of Kentucky Center of Research in Obesity and Cardiovascular Disease COBRE P20 GM103527‐06 to A.S.L.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.