title: 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: 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.
authors.affiliation: Department of Integrative Biology and Physiology, Stress Physiology Center, University of Minnesota, 321 Church St. SE, Minneapolis, MN 55455, USA. rhan@umn.edu
authors.forename: Ruijun
authors.initials: R
authors.lastname: Han
authors.forename: Aiyun
authors.initials: A
authors.lastname: Li
authors.forename: Lijun
authors.initials: L
authors.lastname: Li
authors.forename: Joanna B
authors.initials: JB
authors.lastname: Kitlinska
authors.forename: Zofia
authors.initials: Z
authors.lastname: Zukowska
mesh_terms: D000818:Animals; D059305:Diet, High-Fat; D018753:Diet, Protein-Restricted / Q000009:adverse effects*; D005260:Female; D018149:Glucose Intolerance / Q000235:genetics*; D050152:Intra-Abdominal Fat / Q000378:metabolism*; D007774:Lactation / Q000502:physiology; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D024821:Metabolic Syndrome / Q000235:genetics; D051379:Mice; D009478:Neuropeptide Y / Q000378:metabolism*; D056128:Obesity, Abdominal / Q000209:etiology*; D011247:Pregnancy; D017476:Receptors, Neuropeptide Y / Q000096:biosynthesis*; D015854:Up-Regulation
chemical_list: D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y