title: Maternal protein restriction during pregnancy and lactation alters central leptin signalling, increases food intake, and decreases bone mass in 1 year old rat offspring.
abstract: The effects of perinatal nutrition on offspring physiology have mostly been examined in young adult animals. Aging constitutes a risk factor for the progressive loss of metabolic flexibility and development of disease. Few studies have examined whether the phenotype programmed by perinatal nutrition persists in aging offspring. Persistence of detrimental phenotypes and their accumulative metabolic effects are important for disease causality. This study determined the effects of maternal protein restriction during pregnancy and lactation on food consumption, central leptin sensitivity, bone health, and susceptibility to high fat diet-induced adiposity in 1-year-old male offspring. Sprague-Dawley rats received either a control or a protein restricted diet throughout pregnancy and lactation and pups were weaned onto laboratory chow. One-year-old low protein (LP) offspring exhibited hyperphagia. The inability of an intraperitoneal (i.p.) leptin injection to reduce food intake indicated that the hyperphagia was mediated by decreased central leptin sensitivity. Hyperphagia was accompanied by lower body weight suggesting increased energy expenditure in LP offspring. Bone density and bone mineral content that are negatively regulated by leptin acting via the sympathetic nervous system (SNS), were decreased in LP offspring. LP offspring did not exhibit increased susceptibility to high fat diet induced metabolic effects or adiposity. The results presented here indicate that the programming effects of perinatal protein restriction are mediated by specific decreases in central leptin signalling to pathways involved in the regulation of food intake along with possible enhancement of different CNS leptin signalling pathways acting via the SNS to regulate bone mass and energy expenditure.
authors.affiliation: Department of Pharmaceutical Sciences, Physics and Statistics, University of the Sciences in Philadelphia, Philadelphia, Pennsylvania, USA.
authors.forename: Rani J
authors.initials: RJ
authors.lastname: Qasem
authors.affiliation: Department of Pharmaceutical Sciences, Physics and Statistics, University of the Sciences in Philadelphia, Philadelphia, Pennsylvania, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pharmaceutical Sciences, Physics and Statistics, University of the Sciences in Philadelphia, Philadelphia, Pennsylvania, USA.
authors.forename: Hee Man
authors.initials: HM
authors.lastname: Tang
authors.affiliation: Department of Mathematics, Physics and Statistics, University of the Sciences in Philadelphia, Philadelphia, Pennsylvania, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Pontiggia
authors.affiliation: Department of Pharmaceutical Sciences, Physics and Statistics, University of the Sciences in Philadelphia, Philadelphia, Pennsylvania, USA.
authors.forename: Anil P
authors.initials: AP
authors.lastname: D'mello
mesh_terms: D050154:Adiposity / Q000187:drug effects; D000818:Animals; D001066:Appetite / Q000187:drug effects; D015415:Biomarkers / Q000097:blood; D001823:Body Composition / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects*; D059305:Diet, High-Fat / Q000009:adverse effects; D018753:Diet, Protein-Restricted / Q000009:adverse effects*; D004435:Eating / Q000187:drug effects*; D005260:Female; D007774:Lactation; D020738:Leptin / Q000378:metabolism*; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000097:blood / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D015415:Biomarkers; D020738:Leptin
keywords: areal bone density; central leptin signalling; diet protein restricted; hyperphagia; programming