title: Protein Restriction During the Last Third of Pregnancy Malprograms the Neuroendocrine Axes to Induce Metabolic Syndrome in Adult Male Rat Offspring.
abstract: Metabolic malprogramming has been associated with low birth weight; however, the interplay between insulin secretion disruption and adrenal function upon lipid metabolism is unclear in adult offspring from protein-malnourished mothers during the last third of gestation. Thus, we aimed to study the effects of a maternal low-protein diet during the last third of pregnancy on adult offspring metabolism, including pancreatic islet function and morphophysiological aspects of the liver, adrenal gland, white adipose tissue, and pancreas. Virgin female Wistar rats (age 70 d) were mated and fed a protein-restricted diet (4%, intrauterine protein restricted [IUPR]) from day 14 of pregnancy until delivery, whereas control dams were fed a 20.5% protein diet. At age 91 d, their body composition, glucose-insulin homeostasis, ACTH, corticosterone, leptin, adiponectin, lipid profile, pancreatic islet function and liver, adrenal gland, and pancreas morphology were assessed. The birth weights of the IUPR rats were 20% lower than the control rats (P < .001). Adult IUPR rats were heavier, hyperphagic, hyperglycemic, hyperinsulinemic, hyperleptinemic, and hypercorticosteronemic (P < .05) with higher low-density lipoprotein cholesterol and lower high-density lipoprotein cholesterol, adiponectin, ACTH, and insulin sensitivity index levels (P < .01). The insulinotropic action of glucose and acetylcholine as well as muscarinic and adrenergic receptor function were impaired in the IUPR rats (P < .05). Maternal undernutrition during the last third of gestation disrupts the pancreatic islet insulinotropic response and induces obesity-associated complications. Such alterations lead to a high risk of metabolic syndrome, characterized by insulin resistance, visceral obesity, and lower high-density lipoprotein cholesterol.
authors.affiliation: Laboratory of Secretion Cell Biology, Department of Biotechnology, Cell Biology and Genetics (J.C.deO., R.M.G., R.A.M., L.F.B., A.M., I.P.M., C.C.S.F., A.P., P.C.F.M.), State University of Maringa, Maringá, 87020-900, PR, Brazil; Department of Physiological Sciences (J.C.deO., P.C.L., E.G.deM.), Roberto Alcantara Gomes Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, 20551-030, RJ, Brazil; Institute of Health Sciences (J.C.deO.), Federal University of Mato Grosso, Sinop, 78557-267, MT, Brazil; Department of Physiological Sciences (R.M.G., R.T.), State University of Maringa, Maringá, 87020-900, PR, Brazil; Molecular Signaling Section, Laboratory of Bioorganic Chemistry (L.F.B.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892; and Department of Morphological Sciences (M.R.M.N.), State University of Maringa, Maringá, 87020-900, PR, Brazil.
authors.forename: Júlio Cezar
authors.initials: JC
authors.lastname: de Oliveira
authors.affiliation: Laboratory of Secretion Cell Biology, Department of Biotechnology, Cell Biology and Genetics (J.C.deO., R.M.G., R.A.M., L.F.B., A.M., I.P.M., C.C.S.F., A.P., P.C.F.M.), State University of Maringa, Maringá, 87020-900, PR, Brazil; Department of Physiological Sciences (J.C.deO., P.C.L., E.G.deM.), Roberto Alcantara Gomes Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, 20551-030, RJ, Brazil; Institute of Health Sciences (J.C.deO.), Federal University of Mato Grosso, Sinop, 78557-267, MT, Brazil; Department of Physiological Sciences (R.M.G., R.T.), State University of Maringa, Maringá, 87020-900, PR, Brazil; Molecular Signaling Section, Laboratory of Bioorganic Chemistry (L.F.B.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892; and Department of Morphological Sciences (M.R.M.N.), State University of Maringa, Maringá, 87020-900, PR, Brazil.
authors.forename: Rodrigo Mello
authors.initials: RM
authors.lastname: Gomes
authors.affiliation: Laboratory of Secretion Cell Biology, Department of Biotechnology, Cell Biology and Genetics (J.C.deO., R.M.G., R.A.M., L.F.B., A.M., I.P.M., C.C.S.F., A.P., P.C.F.M.), State University of Maringa, Maringá, 87020-900, PR, Brazil; Department of Physiological Sciences (J.C.deO., P.C.L., E.G.deM.), Roberto Alcantara Gomes Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, 20551-030, RJ, Brazil; Institute of Health Sciences (J.C.deO.), Federal University of Mato Grosso, Sinop, 78557-267, MT, Brazil; Department of Physiological Sciences (R.M.G., R.T.), State University of Maringa, Maringá, 87020-900, PR, Brazil; Molecular Signaling Section, Laboratory of Bioorganic Chemistry (L.F.B.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892; and Department of Morphological Sciences (M.R.M.N.), State University of Maringa, Maringá, 87020-900, PR, Brazil.
authors.forename: Rosiane Aparecida
authors.initials: RA
authors.lastname: Miranda
authors.affiliation: Laboratory of Secretion Cell Biology, Department of Biotechnology, Cell Biology and Genetics (J.C.deO., R.M.G., R.A.M., L.F.B., A.M., I.P.M., C.C.S.F., A.P., P.C.F.M.), State University of Maringa, Maringá, 87020-900, PR, Brazil; Department of Physiological Sciences (J.C.deO., P.C.L., E.G.deM.), Roberto Alcantara Gomes Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, 20551-030, RJ, Brazil; Institute of Health Sciences (J.C.deO.), Federal University of Mato Grosso, Sinop, 78557-267, MT, Brazil; Department of Physiological Sciences (R.M.G., R.T.), State University of Maringa, Maringá, 87020-900, PR, Brazil; Molecular Signaling Section, Laboratory of Bioorganic Chemistry (L.F.B.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892; and Department of Morphological Sciences (M.R.M.N.), State University of Maringa, Maringá, 87020-900, PR, Brazil.
authors.forename: Luiz Felipe
authors.initials: LF
authors.lastname: Barella
authors.affiliation: Laboratory of Secretion Cell Biology, Department of Biotechnology, Cell Biology and Genetics (J.C.deO., R.M.G., R.A.M., L.F.B., A.M., I.P.M., C.C.S.F., A.P., P.C.F.M.), State University of Maringa, Maringá, 87020-900, PR, Brazil; Department of Physiological Sciences (J.C.deO., P.C.L., E.G.deM.), Roberto Alcantara Gomes Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, 20551-030, RJ, Brazil; Institute of Health Sciences (J.C.deO.), Federal University of Mato Grosso, Sinop, 78557-267, MT, Brazil; Department of Physiological Sciences (R.M.G., R.T.), State University of Maringa, Maringá, 87020-900, PR, Brazil; Molecular Signaling Section, Laboratory of Bioorganic Chemistry (L.F.B.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892; and Department of Morphological Sciences (M.R.M.N.), State University of Maringa, Maringá, 87020-900, PR, Brazil.
authors.forename: Ananda
authors.initials: A
authors.lastname: Malta
authors.affiliation: Laboratory of Secretion Cell Biology, Department of Biotechnology, Cell Biology and Genetics (J.C.deO., R.M.G., R.A.M., L.F.B., A.M., I.P.M., C.C.S.F., A.P., P.C.F.M.), State University of Maringa, Maringá, 87020-900, PR, Brazil; Department of Physiological Sciences (J.C.deO., P.C.L., E.G.deM.), Roberto Alcantara Gomes Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, 20551-030, RJ, Brazil; Institute of Health Sciences (J.C.deO.), Federal University of Mato Grosso, Sinop, 78557-267, MT, Brazil; Department of Physiological Sciences (R.M.G., R.T.), State University of Maringa, Maringá, 87020-900, PR, Brazil; Molecular Signaling Section, Laboratory of Bioorganic Chemistry (L.F.B.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892; and Department of Morphological Sciences (M.R.M.N.), State University of Maringa, Maringá, 87020-900, PR, Brazil.
authors.forename: Isabela Peixoto
authors.initials: IP
authors.lastname: Martins
authors.affiliation: Laboratory of Secretion Cell Biology, Department of Biotechnology, Cell Biology and Genetics (J.C.deO., R.M.G., R.A.M., L.F.B., A.M., I.P.M., C.C.S.F., A.P., P.C.F.M.), State University of Maringa, Maringá, 87020-900, PR, Brazil; Department of Physiological Sciences (J.C.deO., P.C.L., E.G.deM.), Roberto Alcantara Gomes Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, 20551-030, RJ, Brazil; Institute of Health Sciences (J.C.deO.), Federal University of Mato Grosso, Sinop, 78557-267, MT, Brazil; Department of Physiological Sciences (R.M.G., R.T.), State University of Maringa, Maringá, 87020-900, PR, Brazil; Molecular Signaling Section, Laboratory of Bioorganic Chemistry (L.F.B.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892; and Department of Morphological Sciences (M.R.M.N.), State University of Maringa, Maringá, 87020-900, PR, Brazil.
authors.forename: Claudinéia Conationi da Silva
authors.initials: CC
authors.lastname: Franco
authors.affiliation: Laboratory of Secretion Cell Biology, Department of Biotechnology, Cell Biology and Genetics (J.C.deO., R.M.G., R.A.M., L.F.B., A.M., I.P.M., C.C.S.F., A.P., P.C.F.M.), State University of Maringa, Maringá, 87020-900, PR, Brazil; Department of Physiological Sciences (J.C.deO., P.C.L., E.G.deM.), Roberto Alcantara Gomes Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, 20551-030, RJ, Brazil; Institute of Health Sciences (J.C.deO.), Federal University of Mato Grosso, Sinop, 78557-267, MT, Brazil; Department of Physiological Sciences (R.M.G., R.T.), State University of Maringa, Maringá, 87020-900, PR, Brazil; Molecular Signaling Section, Laboratory of Bioorganic Chemistry (L.F.B.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892; and Department of Morphological Sciences (M.R.M.N.), State University of Maringa, Maringá, 87020-900, PR, Brazil.
authors.forename: Audrei
authors.initials: A
authors.lastname: Pavanello
authors.affiliation: Laboratory of Secretion Cell Biology, Department of Biotechnology, Cell Biology and Genetics (J.C.deO., R.M.G., R.A.M., L.F.B., A.M., I.P.M., C.C.S.F., A.P., P.C.F.M.), State University of Maringa, Maringá, 87020-900, PR, Brazil; Department of Physiological Sciences (J.C.deO., P.C.L., E.G.deM.), Roberto Alcantara Gomes Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, 20551-030, RJ, Brazil; Institute of Health Sciences (J.C.deO.), Federal University of Mato Grosso, Sinop, 78557-267, MT, Brazil; Department of Physiological Sciences (R.M.G., R.T.), State University of Maringa, Maringá, 87020-900, PR, Brazil; Molecular Signaling Section, Laboratory of Bioorganic Chemistry (L.F.B.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892; and Department of Morphological Sciences (M.R.M.N.), State University of Maringa, Maringá, 87020-900, PR, Brazil.
authors.forename: Rosana
authors.initials: R
authors.lastname: Torrezan
authors.affiliation: Laboratory of Secretion Cell Biology, Department of Biotechnology, Cell Biology and Genetics (J.C.deO., R.M.G., R.A.M., L.F.B., A.M., I.P.M., C.C.S.F., A.P., P.C.F.M.), State University of Maringa, Maringá, 87020-900, PR, Brazil; Department of Physiological Sciences (J.C.deO., P.C.L., E.G.deM.), Roberto Alcantara Gomes Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, 20551-030, RJ, Brazil; Institute of Health Sciences (J.C.deO.), Federal University of Mato Grosso, Sinop, 78557-267, MT, Brazil; Department of Physiological Sciences (R.M.G., R.T.), State University of Maringa, Maringá, 87020-900, PR, Brazil; Molecular Signaling Section, Laboratory of Bioorganic Chemistry (L.F.B.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892; and Department of Morphological Sciences (M.R.M.N.), State University of Maringa, Maringá, 87020-900, PR, Brazil.
authors.forename: Maria Raquel Marçal
authors.initials: MR
authors.lastname: Natali
authors.affiliation: Laboratory of Secretion Cell Biology, Department of Biotechnology, Cell Biology and Genetics (J.C.deO., R.M.G., R.A.M., L.F.B., A.M., I.P.M., C.C.S.F., A.P., P.C.F.M.), State University of Maringa, Maringá, 87020-900, PR, Brazil; Department of Physiological Sciences (J.C.deO., P.C.L., E.G.deM.), Roberto Alcantara Gomes Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, 20551-030, RJ, Brazil; Institute of Health Sciences (J.C.deO.), Federal University of Mato Grosso, Sinop, 78557-267, MT, Brazil; Department of Physiological Sciences (R.M.G., R.T.), State University of Maringa, Maringá, 87020-900, PR, Brazil; Molecular Signaling Section, Laboratory of Bioorganic Chemistry (L.F.B.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892; and Department of Morphological Sciences (M.R.M.N.), State University of Maringa, Maringá, 87020-900, PR, Brazil.
authors.forename: Patrícia Cristina
authors.initials: PC
authors.lastname: Lisboa
authors.affiliation: Laboratory of Secretion Cell Biology, Department of Biotechnology, Cell Biology and Genetics (J.C.deO., R.M.G., R.A.M., L.F.B., A.M., I.P.M., C.C.S.F., A.P., P.C.F.M.), State University of Maringa, Maringá, 87020-900, PR, Brazil; Department of Physiological Sciences (J.C.deO., P.C.L., E.G.deM.), Roberto Alcantara Gomes Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, 20551-030, RJ, Brazil; Institute of Health Sciences (J.C.deO.), Federal University of Mato Grosso, Sinop, 78557-267, MT, Brazil; Department of Physiological Sciences (R.M.G., R.T.), State University of Maringa, Maringá, 87020-900, PR, Brazil; Molecular Signaling Section, Laboratory of Bioorganic Chemistry (L.F.B.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892; and Department of Morphological Sciences (M.R.M.N.), State University of Maringa, Maringá, 87020-900, PR, Brazil.
authors.forename: Paulo Cezar de Freitas
authors.initials: PC
authors.lastname: Mathias
authors.affiliation: Laboratory of Secretion Cell Biology, Department of Biotechnology, Cell Biology and Genetics (J.C.deO., R.M.G., R.A.M., L.F.B., A.M., I.P.M., C.C.S.F., A.P., P.C.F.M.), State University of Maringa, Maringá, 87020-900, PR, Brazil; Department of Physiological Sciences (J.C.deO., P.C.L., E.G.deM.), Roberto Alcantara Gomes Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, 20551-030, RJ, Brazil; Institute of Health Sciences (J.C.deO.), Federal University of Mato Grosso, Sinop, 78557-267, MT, Brazil; Department of Physiological Sciences (R.M.G., R.T.), State University of Maringa, Maringá, 87020-900, PR, Brazil; Molecular Signaling Section, Laboratory of Bioorganic Chemistry (L.F.B.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892; and Department of Morphological Sciences (M.R.M.N.), State University of Maringa, Maringá, 87020-900, PR, Brazil.
authors.forename: Egberto Gaspar
authors.initials: EG
authors.lastname: de Moura
mesh_terms: D000311:Adrenal Glands / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000502:physiology; D002784:Cholesterol / Q000097:blood; D018753:Diet, Protein-Restricted; D004435:Eating / Q000502:physiology; D005260:Female; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D020738:Leptin / Q000097:blood; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena / Q000502:physiology*; D024821:Metabolic Syndrome / Q000209:etiology* / Q000378:metabolism; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001786:Blood Glucose; D007328:Insulin; D020738:Leptin; D002784:Cholesterol