Early Life Stress-Induced Increases in Adiposity in Mice are Prevented by the Adipose Tissue-Specific Abrogation of Neuropeptide Y Receptor 2

Stress has long been associated with the physiology of disease, however, its mechanism of action in obesity remains unknown. Neuropeptide Y (NPY) plays a critical role in the regulation of energy homeostasis acting in the central nervous system as an orexigenic agent resulting in feeding that particularly favors the ingestion of foods rich in carbohydrates. Peripherally, NPY stimulates lipid storage in white adipose tissue (WAT) via NPY receptor 2 (NPY2R) promoting adipocyte precursor proliferation, differentiation of preadipocytes into mature adipocytes, as well as lipogenesis and adipose tissue deposition. Under chronic stress, NPY is co‐released with catecholamines by sympathetic axons to stimulate increased fat storage. We have previously discovered that mice exposed to a model of early life stress, maternal separation and early weaning (MSEW), display increased adiposity at weaning. Thus, we hypothesized that knocking down NPY2R in adipose tissue using the cre‐lox technology could prevent increases in adiposity in mice exposed to MSEW. MSEW was performed by separating adipose tissue‐specific floxed NPYR2 pups from the dam for 4 to 8 hours during postnatal days (PD) 2 to 16, and weaned early on PD 17. Control mice remained undisturbed and were weaned on PD 21. Body weight and echoMRI were performed in all litters at postnatal day 21 and tissue samples were taken for genotyping. Despite no changes in BW, wild type (WT, Y2 floxed) mice exposed to MSEW showed a ~30 % increase in adiposity compared with control WT mice (7.5±0.6 vs. 5.6±0.3 % body fat, p<0.05). However, this increase in adiposity was abrogated in MSEW NPYR2 knock out mice (5.7±0.1 vs. 5.5±0.6 % body fat, p=NS). In addition, WT mice exposed to MSEW showed reduced ratio of the adipose tissue norepinephrine/NPY concentrations and increased NPY2R mRNA expression compared with control mice. Taken together, these data suggest that exposure to postnatal MSEW may induce a shift in co‐transmitter release by catecholaminergic neurons innervating the adipose tissue leading to an increase in adiposity. Support or Funding Information R01HF135158 to ASL, R01HL135158‐01A1S1 to JRL This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .