Maternal low‐protein diet up‐regulates the neuropeptide Y system in visceral fat and leads to abdominal obesity and glucose intolerance in a sex‐ and time‐specific manner

Abstract

ABSTRACT Neuropeptide Y (NPY) mediates stress‐induced obesity in adult male mice by activating its Y2 receptor (Y2R) in visceral adipose tissue (VAT). Here, we studied whether the NPY‐Y2R system is also activated by maternal low‐protein diet (LPD) and linked to obesity in offspring. Prenatal LPD offspring had lower birth weights compared to normal‐protein diet (NPD) offspring. Female prenatal and lactation stress (PLS) offspring from mothers fed an LPD developed abdominal adiposity and glucose intolerance associated with a 5‐fold up‐regulation of NPY mRNA and a 6‐fold upregulation of Y2R mRNA specifically in VAT, in addition to elevated platelet‐rich‐plasma (PRP) NPY, compared to control females fed a high‐fat diet (HFD). Conversely, PLS male offspring showed lower NPY in PRP, a 10‐fold decrease of Y2R mRNA in VAT, lower adiposity, and improved glucose tolerance compared to control males. Interestingly, prenatal LPD offspring cross‐fostered to control lactating mothers had completely inverse metabolic and NPY phenotypes. Taken together, these findings suggested that maternal LPD activates the VAT NPY‐Y2R system and increases abdominal adiposity and glucose intolerance in a sex‐ and time‐specific fashion, suggesting that the peripheral NPY system is a potential mediator of programming for the offspring's vulnerability to obesity and metabolic syndrome.—Han, R., Li, A., Li, L., Kitlinska, J. B., Zukowska, Z. Maternal low‐protein diet up‐regulates the neuropeptide Y system in visceral fat and leads to abdominal obesity and glucose intolerance in a sex‐ and time‐specific manner. FASEB J. 26, 3528–3536 (2012). www.fasebj.org