title: Maternal protein restriction in mice causes adverse metabolic and hypothalamic effects in the F1 and F2 generations.
abstract: Maternal protein restriction causes metabolic alterations associated with hypothalamic dysfunction. Because the consequences of metabolic programming can be passed transgenerationally, the present study aimed to assess whether maternal protein restriction alters the expression of hypothalamic neuropeptides in offspring and to evaluate hormonal and metabolic changes in male offspring from the F1 and F2 generations. Female Swiss mice (F0) were mated and fed either a normal-protein (NP group; 19 % protein) or a low-protein (LP group; 5 % protein) diet throughout gestation of the F1 generation (NP1 and LP1). At 3 months of age, F1 females were mated to produce the F2 generation (NP2 and LP2). Animals from all groups were evaluated at 16 weeks of age. LP1 offspring had significantly lower weights and shorter lengths than NP1 offspring at birth, but they underwent a phase of rapid catch-up growth. Conversely, the LP2 offspring were not significantly different from the NP2 offspring in either weight or length. At 16 weeks, no differences were found in body mass among any of the groups, although LP1 and LP2 offspring showed hypercholesterolaemia, hypertriacylglycerolaemia, hyperglycaemia, glucose intolerance, insulin resistance, increased levels of insulin, leptin and resistin, decreased endogenous leptin sensitivity, increased adiposity with elevated leptin levels and leptin resistance characterised by altered expression of neuropeptide Y and pro-opiomelanocortin without any changes in the leptin receptor Ob-Rb. We conclude that severe maternal protein restriction promotes metabolic programming in F1 and F2 male offspring due to a dysregulation of the adipoinsular axis and a state of hypothalamic leptin resistance.
authors: Laboratory of Morphometry and Cardiovascular Morphology, Biomedical Center, Institute of Biology, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors: Nayara
authors: N
authors: Peixoto-Silva
authors: Eliete Dalla Corte
authors: ED
authors: Frantz
authors: Carlos Alberto
authors: CA
authors: Mandarim-de-Lacerda
authors: Alessandra
authors: A
authors: Pinheiro-Mulder
mesh_terms: D000818:Animals; D001724:Birth Weight; D001835:Body Weight; D018753:Diet, Protein-Restricted; D005260:Female; D006128:Growth; D007031:Hypothalamus / Q000378:metabolism*; D020738:Leptin / Q000378:metabolism*; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D008659:Metabolic Diseases / Q000209:etiology* / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D009478:Neuropeptide Y / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011488:Protein Deficiency / Q000150:complications*; D054411:Receptors, Leptin / Q000378:metabolism
chemical_list: D020738:Leptin; D009478:Neuropeptide Y; D054411:Receptors, Leptin