Early life stress reduces in vivo lipolysis efficiency in female mice fed a high fat diet

Previously, we have shown that female mice exposed to maternal separation and early weaning (MSEW), a model of postnatal neglect, increases fat mass and worsens the cardiometabolic function in response to high fat diet (HF) feeding. We also found that β3 adrenergic receptor mRNA expression, involved in local lipolysis stimulation, was reduced in gonadal white adipose tissue (gWAT). Thus, the aim of this study was to test the hypothesis that female MSEW mice display reduced lipolysis in‐vivo and in‐vitro. MSEW was performed by separating the pups from the mother for periods of 4–8 hr during postnatal days 2–16. Mice were weaned at P17. Control mice remained undisturbed in the home cage all times and weaned at P21. At weaning, mice were placed on a low fat (10% kcal from fat) or high fat (60% kcal from fat) diet for 16 weeks. At week 14, an in‐vivo lipolysis test was performed by injecting with 1mg/kg BW of isoproterenol, IP. Free fatty acids (FFA) were measured in plasma obtained after 15 minutes of the injection. At week 16, an in‐vitro lipolysis test was performed in gWAT. As such, gWAT was removed from female control and MSEW mice, weighed, and washed with ice‐cold PBS. In‐vitro lipolysis was performed in the presence or absence of isoproterenol (10uM, Sigma Aldrich). Free glycerol kit (Sigma Aldrich) was used to measure lipolytic products and results were normalized to tissue weight. In‐vivo, FFAs were reduced in female MSEW mice fed a HF (102±13 uM/ml) when compared with controls (144±24 uM/ml, p=0.066). In‐vitro, we found similar free glycerol levels in control and MSEW mice fed a LF (9.2±0.8 vs. 10.5±1.4 mg/dl/g tissue, respectively). Although HF reduced isoproterenol‐induced free glycerol levels, control and MSEW mice showed not statistically significant differences (4.4±0.6 vs. 3.5±0.6 mg/dl/g tissue, respectively). Taken together, these data indicate that HF reduced lipolysis capacity either in control and MSEW mice. Also, MSEW reduced lipolysis when determined in‐vivo conditions, suggesting that neuroendocrine and autonomic factors may be implicated in the mechanism by which MSEW mice are prone to increase fat mass. Support or Funding Information This 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 .