Correlation of serum leptin and insulin levels of pregnant protein-restricted rats with predictive obesity variables

During pregnancy and protein restriction, changes in serum insulin and leptin levels, food intake and several metabolic parameters normally result in enhanced adiposity. We evaluated serum leptin and insulin levels and their correlations with some predictive obesity variables in Wistar rats (90 days), up to the 14th day of pregnancy: control non-pregnant (N = 5) and pregnant (N = 7) groups (control diet: 17% protein), and low-protein non-pregnant (N = 5) and pregnant (N = 6) groups (low-protein diet: 6%). Independent of the protein content of the diet, pregnancy increased total (F1,19 = 22.28, P < 0.001) and relative (F1,19 = 5.57, P < 0.03) food intake, the variation of weight (F1,19 = 49.79, P < 0.000) and final body weight (F1,19 = 19.52, P < 0.001), but glycemia (F1,19 = 9.02, P = 0.01) and the relative weight of gonadal adipose tissue (F1,19 = 17.11, P < 0.001) were decreased. Pregnancy (F1,19 = 18.13, P < 0.001) and low-protein diet (F1,19 = 20.35, P < 0.001) increased the absolute weight of brown adipose tissue. However, the relative weight of this tissue was increased only by protein restriction (F1,19 = 15.20, P < 0.001) and the relative lipid in carcass was decreased in low-protein groups (F1,19 = 4.34, P = 0.05). Serum insulin and leptin levels were similar among groups and did not correlate with food intake. However, there was a positive relationship between serum insulin levels and carcass fat depots in low-protein groups (r = 0.37, P < 0.05), while in pregnancy serum leptin correlated with weight of gonadal (r = 0.39, P < 0.02) and retroperitoneal (r = 0.41, P < 0.01) adipose tissues. Unexpectedly, protein restriction during 14 days of pregnancy did not alter the serum profile of adiposity signals and their effects on food intake and adiposity, probably due to the short term of exposure to low-protein diet.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Brazilian Foundations FAPEMATUniversidade Federal de Mato Grosso Faculdade de Ciências MédicasUniversidade Federal de Mato Grosso Faculdade de Nutrição Departamento de Alimentos e NutriçãoUniversidade Estadual de Campinas Instituto de Biologia Departamento de Fisiologia e BiofísicaUniversidade Federal de São Paulo (UNIFESP) Departamento de Fisiologia da NutriçãoUNIFESP, Depto. de Fisiologia da NutriçãoBrazilian Foundations FAPEMAT: 175/04CNPq: 479138/2003-6SciEL

Nutritional Recovery with a Soybean Diet after Weaning Reduces Lipogenesis but Induces Inflammation in the Liver in Adult Rats Exposed to Protein Restriction during Intrauterine Life and Lactation

We evaluated the effects of postweaning nutritional recovery with a soybean flour diet on de novo hepatic lipogenesis and inflammation in adult rats exposed to protein restriction during intrauterine life and lactation. Rats from mothers fed with protein (casein) in a percentage of 17% (control, C) or 6% (low, L) during pregnancy and lactation were fed with diet that contained 17% casein (CC and LC groups, resp.) or soybean (CS and LS groups, resp.) after weaning until 90 days of age. LS and CS rats had low body weight, normal basal serum triglyceride levels, increased ALT concentrations, and high HOMA-IR indices compared with LC and CC rats. The soybean diet reduced PPARγ as well as malic enzyme and citrate lyase contents and activities. The lipogenesis rate and liver fat content were lower in LS and CS rats relative to LC and CC rats. TNFα mRNA and protein levels were higher in LS and CS rats than in LC and CC rats. NF-κB mRNA levels were lower in the LC and LS groups compared with the CC and LC groups. Thus, the soybean diet prevented hepatic steatosis at least in part through reduced lipogenesis but resulted in TNFα-mediated inflammation

Effect of soybean flour in the nutritional recovery and in the insulin secretion of rats submitted to protein restriction during pregnancy and lactation period

Orientadores: Everardo Magalhães Carneiro, Marcia Queiroz LatorracaTese (doutorado) - Universidade Estadual de Campinas, Instituto de BiologiaResumo: A restrição protéica materna reduz o crescimento e promove alterações permanentes na estrutura e função de órgãos da prole, contribuindo para o desenvolvimento de doenças cardiovasculares, obesidade e diabetes. O consumo de alimentos à base de soja está associado a um menor risco de desenvolver diabetes pelo seu conteúdo de isoflavonas e pela composição de aminoácidos de sua proteína que contribuem para uma melhora na secreção de insulina. Tem sido sugerido que a genisteína, uma isoflavona da soja, modula a secreção de insulina através das vias AMPc/PKA e PLC/PKC. Deste modo, nós avaliamos o valor biológico da dieta à base de farinha de soja e seus efeitos sobre o crescimento de órgãos, o perfil de aminoácidos, insulina e metabólitos séricos em ratos submetidos à restrição protéica na infância e recuperados com essa dieta após o desmame, bem como o efeito da dieta à base de soja sobre a secreção de insulina em resposta a glicose e a ativadores do adenilato ciclase e proteína quinase C, além da expressão da PKAa e PKCa em ilhotas pancreáticas de ratos adultos. Ratos de mães alimentadas com 17% ou 6% de proteína (caseína) durante a gestação e lactação foram mantidos com dieta contendo 17% de proteína à base de caseína (grupos CC e RC) ou dieta com 17% de proteína à base de farinha de soja (grupos CS e RS) e dieta com 6% de proteína (grupo HP). Após 90 dias de idade, proles de mães alimentadas com dieta hipoprotéica exibiram déficit permanente de peso corpóreo e de concentrações séricas de insulina, taurina, glutamina, fenilserina e lisina, porém apresentaram um aumento no peso relativo dos órgãos, exceto do fígado. A dieta à base de farinha de soja reduziu o peso relativo do fígado e aumentou as concentrações séricas de insulina, taurina, ornitina e fenilserina. Embora ratos recuperados com soja (RS) tenham ingerido mais dieta proporcionalmente ao peso corpóreo do que os ratos recuperados com caseína (RC) eles mostraram menor coeficiente de eficácia alimentar, e resultou em peso corpóreo final similar entre esses grupos. As concentrações séricas de albumina e proteínas totais não diferiram entre os grupos RS e RC. A dieta à base de soja melhorou a resposta de células beta de ratos controles em concentrações fisiológicas de glicose, enquanto em ilhotas de ratos recuperados isso ocorreu na presença de concentrações suprafisiológicas de glicose. A presença de PMA induziu uma resposta secretória com potência similar em ilhotas dos grupos RS e CS e a expressão de PKC foi similar em todos os grupos, exceto no grupo HP, que expressou menores concentrações dessa proteína. A adição de forskolin ao meio de incubação aumentou a secreção de insulina em ratos recuperados e naqueles mantidos com caseína e a expressão de PKAa foi maior no grupo RS em relação ao grupo CS. Esses resultados sugerem que dieta à base de farinha de soja é capaz de promover a recuperação nutricional em animais submetidos à restrição protéica em fases críticas de desenvolvimento, melhorando o perfil de aminoácidos séricos que estimulam a secreção de insulina. Além disso, a melhora na secreção de insulina parece não ser devido a ativação das vias AMPc/PKA e inositol fosfato/PKCAbstract: Maternal protein restriction leads to reduction in the growth of organs, permanent changes in their structure and functions contributing to development of cardiovascular disease, obesity and diabetes. Consumption of soy-based foods is associated to lower risk of diabetes by its isoflavone content and amino acid composition of its protein that contribute to improve of insulin secretion. It has been suggested that genistein, soy isoflavone, modulates the insulin secretion through of cAMP/PKA and PLC/PKC pathways. Thus, we evaluated the biological value of soybean flour diet and its effects on organ growth, serum amino acids, insulin and metabolites profile in rats submitted to protein restriction in early life and recovered with those diet after weaning, as well as, the effect of soybean diet on insulin secretion in response to glucose and activators of adenylate cyclase and PKC, besides the expression of PKA and PKC in pancreatic islets from adult rats. Rats from mothers fed with 17% or 6% protein (casein) during pregnancy and lactation were maintained with 17% casein (CC and CR groups) or soybean (SC and SR groups) diet and with 6% casein (LP groups) diet. At 90d of age offspring of protein-restricted-mothers exhibited permanent deficit of body weight, serum insulin, taurine, glutamine, phenylserine and lysine concentrations, but increased relative organs¿ weight, except liver. Soybean flour diet reduced the relative liver weight and increased serum insulin, taurine, ornithine and phenylserine concentrations. Although SR rats had eaten proportionally to body weight more diet than CR rats they showed lower feed conversion efficiency which resulted in the final body weight similar between these groups. The SR and CR also exhibited similar serum albumin and protein concentrations. Soybean diet improved the response of ß-cells from control rats to a physiological concentration of glucose, whereas in islets from recovered rats this occurred in presence of a supra-physiological glucose concentration. PMA induced similar potent secretory response in islets from SR and SC groups and PKC expression was similar in all groups, except LP that expressed lower levels this protein. Forskolin increased the insulin secretion in recovered rats and in those maintained with casein diet and PKA expression was higher in SR than in SC rats. These results suggest that soybean flour diet is able to promote the nutritional recovery in animals submitted to protein restriction in critical phase of development improving serum amino acid levels that have the stimulatory effect on insulin release. Moreover the improve of insulin secretion seemed does not to be due the activation of the cAMP/PKA and inositol phosphate/PKC pathwaysDoutoradoFisiologiaDoutor em Biologia Funcional e Molecula

Nutritional Recovery with a Soybean Diet after Weaning Reduces Lipogenesis but Induces Inflammation in the Liver in Adult Rats Exposed to Protein Restriction during Intrauterine Life and Lactation

We evaluated the effects of postweaning nutritional recovery with a soybean flour diet on de novo hepatic lipogenesis and inflammation in adult rats exposed to protein restriction during intrauterine life and lactation. Rats from mothers fed with protein (casein) in a percentage of 17% (control, C) or 6% (low, L) during pregnancy and lactation were fed with diet that contained 17% casein (CC and LC groups, resp.) or soybean (CS and LS groups, resp.) after weaning until 90 days of age. LS and CS rats had low body weight, normal basal serum triglyceride levels, increased ALT concentrations, and high HOMA-IR indices compared with LC and CC rats. The soybean diet reduced PPARγ as well as malic enzyme and citrate lyase contents and activities. The lipogenesis rate and liver fat content were lower in LS and CS rats relative to LC and CC rats. TNFα mRNA and protein levels were higher in LS and CS rats than in LC and CC rats. NF-κB mRNA levels were lower in the LC and LS groups compared with the CC and LC groups. Thus, the soybean diet prevented hepatic steatosis at least in part through reduced lipogenesis but resulted in TNFα-mediated inflammation

A Low-protein Diet During Pregnancy Prevents Modifications In Intercellular Communication Proteins In Rat Islets.

Gap junctions between β-cells participate in the precise regulation of insulin secretion. Adherens junctions and their associated proteins are required for the formation, function and structural maintenance of gap junctions. Increases in the number of the gap junctions between β-cells and enhanced glucose-stimulated insulin secretion are observed during pregnancy. In contrast, protein restriction produces structural and functional alterations that result in poor insulin secretion in response to glucose. We investigated whether protein restriction during pregnancy affects the expression of mRNA and proteins involved in gap and adherens junctions in pancreatic islets. An isoenergetic low-protein diet (6% protein) was fed to non-pregnant or pregnant rats from day 1-15 of pregnancy, and rats fed an isocaloric normal-protein diet (17% protein) were used as controls. The low-protein diet reduced the levels of connexin 36 and β-catenin protein in pancreatic islets. In rats fed the control diet, pregnancy increased the levels of phospho-[Ser(279/282)]-connexin 43, and it decreased the levels of connexin 36, β-catenin and beta-actin mRNA as well as the levels of connexin 36 and β-catenin protein in islets. The low-protein diet during pregnancy did not alter these mRNA and protein levels, but avoided the increase of levels of phospho-[Ser(279/282)]-connexin 43 in islets. Insulin secretion in response to 8.3 mmol/L glucose was higher in pregnant rats than in non-pregnant rats, independently of the nutritional status. Short-term protein restriction during pregnancy prevented the Cx43 phosphorylation, but this event did not interfer in the insulin secretion.48