Consequences on anthropometry and metabolism of offspring maintenance with low-protein diet since pregnancy to adult age / Consequências sobre a antropometria e o metabolismo em ratos submetidos a dieta com baixo teor de proteínas da gravidez até a idade adulta


  • Elizabeth do Nascimento Brazilian Journals Publicações de Periódicos, São José dos Pinhais, Paraná
  • Laércio Marques da Luz Neto
  • Nathália Cavalcanti de Morais Araújo
  • Eryvelton de Souza Franco
  • Giselia de Santana Muniz



low-protein diet, catch-up growth, metabolismo, rats.


The pre and early post natal is a period high susceptible to environmental insults for instance nutrition. There is a high metabolic demand necessary for the multiplication and differentiation of cells for the formation of tissues and organs and unbalanced diets affect metabolism at long term. The present study aimed to analyze physiological and metabolic parameters in male offspring submitted to the low protein diet in the perinatal life followed by a normoprotein diet or kept on the same maternal low protein diet after weaning. 12 female Wistar rats were matched with male of same strainand according maternal diet forming normoproteic and low-protein groups during gestation and lactation. At weaning three groups were randomly formed: CC (control-control), LP (low-protein-low protein) and LPC (low-protein-control). Somatic growth, feed intake, organ weight, biochemical parameters, liver fat, blood cell count and glucose tolerance test were analysed. The post-weaning "nutritional recovery" diet improved body mass and longitudinal length. But, the maintenance with low protein diet post weaning caused weight and length deficiency (P<0.001). Other parameters such as food intake, murinometric measurements, fasting gliscemia, visceral fat, organ weight, OGTT and biochemical parameters observed in the LPC were similar to CC. The LP groups caused lower area under the glycemic curve, lower visceral fat, but similar blood count, tibial growth and liver fat compared to control. The parameters evaluated in offspring submitted to nutritional recovery corroborate previous study, but the maintenance of offspring with low protein diet minimizes catch-up growth, but alters metabolic response to glucose.


Abad V, Uyeda JA, Temple HT, De Luca F, Baron J. Determinants of spatial polarity in the growth plate. Endocrinology. 140(2): 958-962, 1999.

Alexandre-Gouabau M C, Bailly E, Coupé B, Le Drean G, Rogniaux HJ, Parnet P. Postnatal growth velocity modulates alterations of proteins involved in metabolism and neuronal plasticity in neonatal hypothalamus in rats born with intrauterine growth restriction. J Nutr Biochem. 23(2): 140-152, 2012. doi:10.1016 / j.jnutbio.2010.11.008

Ballock RT, O'Keefe RJ. Physiology and pathophysiology of the growth plate. Birth Defects Res C Embryo Today. 69(2): 123-143, 2003.

Barker, D J. The malnourished baby and infant. Br Med Bull 60: 69-88, 2001. doi: 10.1093 / bmb / 60.1.69

Barker D J. The origins of the developmental origins theory. J Intern Med. 261(5): 412-417, 2007.

Bayne K. Revised Guide for the Care and Use of Laboratory Animals available. Americ Physiolog Soc. The Physiologist. 39(4): 199-208, 1996.

Bayol S, Jones D, Goldspink G, Stickland NC. The influence of undernutrition during gestation on skeletal muscle cellularity and on the expression of genes that control muscle growth. Br J Nutr. 91(3): 331-339, 2004. DOI: 10.1079 / BJN20031070

Bellinger L, Lilley C, Langley-Evans SC. Prenatal exposure to a maternal low-protein diet programmes a preference for high-fat foods in the young adult rat. Br J Nutr. 92(3): 513-520, 2004. doi: 10.1079 / bjn20041224

Berends LM, Fernandez-Twinn DS, Martin-Gronert MS, Cripps RL, Ozanne SE. Catch-up growth following intra-uterine growth-restriction programmes an insulin-resistant phenotype in adipose tissue. Int J Obes (Lond). 37(8): 1051-1057, 2013. doi: 10.1038/ijo.2012.196

Bharne A P, Borkar CD, Subhedar NK, Kokare DM. Differential expression of CART in feeding and reward circuits in binge eating rat model. Behav Brain Res. 291: 219-231, 2015. DOI: 10.1016 / j.bbr.2015.05.030

Bugianesi E, Moscatiello S, Ciaravella MF, Marchesini G. Insulin resistance in nonalcoholic fatty liver disease. Curr Pharm Des. 16(17): 1941-1951, 2010. doi: 10.2174/38161210791208875

Carr S K, Chen JH, Cooper WN, Constância M, Yeo GSH, Ozanne SE. Maternal diet amplifies the hepatic aging trajectory of Cidea in male mice and leads to the development of fatty liver. The FASEB Journal. 28 (5): 2191-2201, 2014.

Coupe, B., Grit I, Darmaun D, Parnet P. The timing of "catch-up growth" affects metabolism and appetite regulation in male rats born with intrauterine growth restriction. Am J Physiol Regul Integr Comp Physiol. 297(3): R813-824, 2009. doi:10.1152 / ajpregu.00201.2009

Dahri S, Snoeck A, Reusens-Billen B, Remacle C, Hote JJ. Islet function in offspring of mothers on low-protein diet during gestation. Diabetes. 40 (Suppl 2): 115-120, 1991. doi:

Santana Muniz, G, Silva AMA, Cavalcanti TCF, França AKS, Ferraz KM, Nascimento E. Early physical activity minimizes the adverse effects of a low-energy diet on growth and development parameters. Nutr Neurosci. 16(3): 113-124, 2013. doi: 10.1179/1476830512Y.0000000037.

Nascimento E, Santana Muniz G, Santana Muniz MG, Alexandre LS, Rocha LS, Leandro CG, Castro RM, Bolaños-Jimenez F. Unlimited access to low-energy diet causes acute malnutrition in dams and alters biometric and biochemical parameters in offspring. J Dev Orig Health Dis. 5(1): 45-55, 2014.

Dudele A, Lund S, Jessen N, Wegener G, et al. Maternal protein restriction before pregnancy reduces offspring early body mass and affects glucose metabolism in C57BL/6JBom mice. J Dev Orig Health Dis. 3(5): 364-374, 2012. DOI:

Even-Zohar N, Jacob J, Amariglio N, Rechavi G, Potievsky O, Philip M, Gat-Yablonski G. Nutrition-induced catch-up growth increases hypoxia inducible factor 1alpha RNA levels in the growth plate. Bone. 42(3): 505-515, 2008. doi: 10.1016 / j.bone.2007.10.015

Gluckman PD, Hanson MA. The developmental origins of the metabolic syndrome. Trends Endocrinol Metab. 15(4): 183-187, 2004. doi 10.1016 / j.tem.2004.03.002

Gluckman PD, Hanson MA. Developmental plasticity and human disease: research directions. J Intern Med. 261(5): 461-471, 2007. doi: 10.1111 / j.1365-2796.2007.01802.x

Gluckman PD, Hanson MA, Spencer HG. Predictive adaptive responses and human evolution. Trends Ecol Evol. 20(10): 527-533, 2005. doi:10.1016 / j.tree.2005.08.001

Guzman-Quevedo O, Silva Aragao R, Garcia GP, Matos RJB, Oliveira ASB, Bolaños-Jiménez F. Impaired hypothalamic mTOR activation in the adult rat offspring born to mothers fed a low-protein diet. PLoS One 8(9): e74990, 2013.

Hales C N, Barker DJ, Clark PM, Cox LJ, Fall C, Osmond C, Winter PD. Fetal and infant growth and impaired glucose tolerance at age 64." BMJ 303(6809): 1019-1022, 1991. doi: 10.1136 / bmj.303.6809.1019

Hunziker EB, Schenk RK. Physiological mechanisms adopted by chondrocytes in regulating longitudinal bone growth in rats. J Physiol. 414: 55-71, 1989.

Instituto Adolfo Lutz. Métodos físico-químicos para análise de alimentos /coordenadores Odair Zenebon, Neus Sadocco Pascuet e Paulo Tiglea -- São Paulo: Instituto Adolfo Lutz, 2008.

Jimenez-Chillaron J C, Ramon- Krauel M, Ribo S, Diaz R. Transgenerational epigenetic inheritance of diabetes risk as a consequence of early nutritional imbalances. Proceedings of the Nutrition Society, v. 75, n. 1, p. 78–89, 2016. doi:

Latorraca MQ, Carneiro EM, Mello MAR, Boschero AC. Reduced insulin secretion in response to nutrients in islets from malnourished young rats is associated with a diminished calcium uptake. J Nutr Biochem. 10(1): 37-43, 1999.

Le Floch J P, Escuyer P, Baudin E, Baudon D, Perlemuter L. Blood glucose area under the curve. Methodological aspects. Diabetes Care 13(2): 172-175, 1990.

Lesage J, Sebaai N, Leonhardt M., Dutriez-Casteloot I, Breton C, Deloof S, Vieau D. Perinatal maternal undernutrition programs the offspring hypothalamo-pituitary-adrenal (HPA) axis. Stress 9(4): 183-198. doi: 10.1080 / 10253890601056192

Liu D, Veit HP, Wilson JH, Denbow DM. Maternal dietary lipids alter bone chemical composition, mechanical properties, and histological characteristics of progeny of Japanese quail. Poult Sci 82(3): 463-473, 2003.

Martins J, Olorunju SAS, Murray LM, Pillay TS. Comparison of equations for the calculation of LDL-cholesterol in hospitalized patients. Clin Chim Acta. 444: 137-142, 2015. doi: 10.1016 / j.cca.2015.01.037

Mathews CE, Xue S, Posgai A, Lightfoot YL, Li X, Lin A, Wasserfall C, Haller MJ, Schatz D, Atkinson AA. Acute Versus Progressive Onset of Diabetes in NOD Mice: Potential Implications for Therapeutic Interventions in Type 1 Diabetes. Diabetes 64(11): 3885-3890, 2015. doi: 10.2337 / db15-0449

Nakamoto T, Miller SA. The effect of protein-energy malnutrition on the development of bones in newborn rats. J Nutr. 109(8): 1469-1476, 1979.

Norman A M, Miles-Chan JL, Thompson NM, Breier BH, Huber K. Postnatal development of metabolic flexibility and enhanced oxidative capacity after prenatal undernutrition. Reprod Sci. 19(6): 607-614, 2012. doi:10.1177 / 1933719111428519

Orman M A, Androulakis IP, Berthiaume F, Ierapetritou M. Metabolic network analysis of perfused livers under fed and fasted states: incorporating thermodynamic and futile-cycle-associated regulatory constraints. J Theor Biol 293: 101-110, 2012.doi: 10.1016 / j.jtbi.2011.10.019

Orozco-Solis R, Lopes de Souza S, Barbosa RJ, Grit I, Le Volch J, Nguyen P, Manhães de Castro, R, Bolaños-Jiménez F. Perinatal undernutrition-induced obesity is independent of the developmental programming of feeding. Physiol Behav. 96(3): 481-492, 2009.

Ozanne SE, Jensen CB, Tingey kJ, Storgaard H, Madsbad S, Vaag AA. Low birthweight is associated with specific changes in muscle insulin-signalling protein expression. Diabetologia. 48(3): 547-552, 2005. doi: 10.1007 / s00125-005-1669-7

Ozanne SE, Smith GD, Tikerpae J, Hales CN. Altered regulation of hepatic glucose output in the male offspring of protein-malnourished rat dams. Am J Physiol. 270(4 Pt 1): E559-564, 1996. doi: 10.1152 / ajpendo.1996.270.4.E559

Ravelli GP, Stein ZA, Susser MW. Obesity in young men after famine exposure in utero and early infancy. N Engl J Med. 295(7): 349-353, 1976. doi: 10.1056/EJM197608122950701

Reeves PG. Components of the AIN-93 Diets as Improvements in the AIN-76A Diet. The Journal of Nutrition. 127 (5): 838S–841S, 1997.

Reeves PG, Nielsen FH, Fahey GC. AIN-93 Purified Diets for Laboratory Rodents: Final Report of the American Institute of Nutrition Ad Hoc Writing Committee on the Reformulation of the AIN-76A Rodent Diet. The Journal of Nutrition, v. 123, n. 11, p. 1939–1951, 1993.

Song, L, Johnson MD, Tamashiro K.L.K. Maternal and Epigenetic Factors That Influence Food Intake and Energy Balance in Offspring. Appetite and Food Intake: Central Control. 2nd edition, 2017.

Symonds M E, Sebert SP, Budge H.The impact of diet during early life and its contribution to later disease: critical checkpoints in development and their long-term consequences for metabolic health. Proc Nutr Soc 68(4): 416-421, 2009. doi:10.1017 / S0029665109990152

Von Ehr, J. and Von Versen-Hoynck F. Implications of maternal conditions and pregnancy course on offspring's medical problems in adult life. Arch Gynecol Obstet. 294(4): 673-679, 2016. doi: 10.1007 / s00404-016-4178-7

West-Eberhard M J. Evolution in the light of developmental and cell biology, and vice versa. Proc Natl Acad Sci U S A 95(15): 8417-8419, 1998. doi: 10.1073 / pnas.95.15.8417.

Zheng J, Xiao X, Zhang Q, Wang T, Yu M, Xu J. Maternal low-protein diet modulates glucose metabolism and hepatic microRNAs expression in the early life of offspring. Nutrients. 9 (3): 205, 2017. doi: 10.3390 / nu9030205.

Ziegler EE. Nutrient Needs for Catch-Up Growth in Low-Birthweight Infants. Nestle Nutr Inst Workshop Ser. 81: 135-143, 2015. doi: 10.1159/000365902.






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