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

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 up-regulation 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