Early exposure to distinct sources of lipids affects differently the development and hepatic inflammatory profiles of 21-day-old rat offspring

Introduction: Maternal diet composition of fatty acids during pregnancy and lactation seems to modify the fetal programming, epigenetic pattern and offspring phenotype. Aim: Herein, we investigated the effects of maternal consumption of normal-fat diets with distinct lipid sources during pregnancy and lactation on the somatic development and proinflammatory status of 21-day-old rat offspring. Materials and Methods: On the first day of pregnancy, female Wistar rats were divided into four groups as follows: soybean oil (M-SO), lard (M-L), hydrogenated vegetable fat (M-HVF) and fish oil (M-FO). Diets were maintained during pregnancy and lactation. Male offspring constituted the SO, L, HVF and FO groups. Pups were weighed and measured weekly. Lipopolysaccharide serum concentration was determined. Tumor necrosis factor alpha, interleukin (IL)-6 and IL-10 in the liver were evaluated by enzyme-linked immunosorbent assay. Liver gene expressions were determined by real-time polymerase chain reaction. Protein expressions in the liver were analyzed by Western blotting. Results: We observed an increase in body weight and adiposity in L and HVF groups. Moreover, HVF group showed an increase in the toll-like receptor 4 mRNA levels, IL10R alpha and phosphorylated form of I kappa B kinase (IKKp-IKK alpha+beta) protein expression. The FO group presented a decrease in body weight, relative weight of retroperitoneal adipose tissue, ADIPOR2 gene expression, lipopolysaccharide and p-IKK alpha+beta and phosphorylated form of nuclear transcription factor kappa B (NF kappa B) p50 (p-NF kappa B p50) protein expression. Conclusion: Summarily, whereas maternal intake of normal-fat diets based on L and HVF appear to affect the somatic development negatively, only early exposure to HVF impairs the pups' proinflammatory status. In contrast, maternal diets based on FO during pregnancy and lactation have been more beneficial to the adiposity and toll-like receptor 4 signaling pathway of the 21-day-old rat offspring, particularly when compared to L or HVF diets.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fed Univ Sao Paulo UNIFESP, PhD Program Interdisciplinar Hlth Sci, Santos, SP, BrazilFed Univ Sao Paulo UNIFESP, Discipline Nutr Physiol, Dept Physiol, Sao Paulo, SP, BrazilFed Univ Sao Paulo UNIFESP, Inst Hlth & Soc, Dept Biosci, Santos, SP, BrazilFed Univ Sao Paulo UNIFESP, PhD Program Interdisciplinar Hlth Sci, Santos, SP, BrazilFed Univ Sao Paulo UNIFESP, Discipline Nutr Physiol, Dept Physiol, Sao Paulo, SP, BrazilFed Univ Sao Paulo UNIFESP, Inst Hlth & Soc, Dept Biosci, Santos, SP, BrazilFAPESP: 2014/10683-0Web of Scienc

Hydrogenated fat diet intake during pregnancy and lactation modifies the PAI-1 gene expression in white adipose tissue of offspring in adult life

We examine whether feeding pregnant and lactating rats hydrogenated fats rich in trans fatty acids modifies the plasma lipid profiles and the expression of adipokines involved with insulin resistance and cardiovascular disease in their 90-day-old offspring. Pregnant and lactating Wistar rats were fed with either a control diet (C group) or one enriched with hydrogenated vegetable fat (T group). Upon weaning, the male pups were sorted into four groups: CC, mothers were receiving C and pups were kept on C; CT, mothers were receiving C and pups were fed with T; TT, mothers were receiving T and pups were kept on T; TC, mothers were receiving T and pups were fed with C. Pups' food intake and body weight were quantified weekly and the pups were killed at day 90 of life by decapitation. Blood and carcass as well as retroperitoneal, epididymal, and subcutaneous white adipose tissues were collected. Food intake and body weight were lower in TC and TT, and metabolic efficiency was reduced in TT. Offspring of TT and TC rats had increased white adipose tissue PAI-1 gene expression. Insulin receptor was higher in TT than other groups. Ingestion of hydrogenated vegetable fat by the mother during gestation and lactation could promote deleterious consequences, even after the withdrawal of the causal factor

Supplementing alpha-tocopherol (vitamin E) and vitamin D3 in high fat diet decrease IL-6 production in murine epididymal adipose tissue and 3T3-L1 adipocytes following LPS stimulation

<p>Abstract</p> <p>Background</p> <p>It is well known that high fat diets (HFDs) induce obesity and an increase in proinflammatory adipokines. Interleukin-6 (IL-6) is considered the major inflammatory mediator in obesity. Obesity is associated with a vitamin deficiency, especially of vitamins E and D3. We examined the effects of vitamin D3 and vitamin E supplementation on levels of IL-6 and IL-10 (as a marker of anti-inflammatory cytokines since, a balance between pro- and anti-inflammatory cytokines is maintained) protein expression in adipose tissue of mice provided with an HFD. Additionally, we measured the effects of vitamin E and vitamin D3 treatment on LPS-stimulated 3T3-L1 adipocytes IL-6 and IL-10 secretion.</p> <p>Results</p> <p>IL-6 protein levels and the IL-6/IL-10 ratio were decreased in epididymal white adipose tissue in groups receiving vitamins E and D3 supplementation compared to the HFD group. A 24-hour treatment of vitamin D3 and vitamin E significantly reduced the IL-6 levels in the adipocytes culture medium without affecting IL-10 levels.</p> <p>Conclusions</p> <p>Vitamin D3 and vitamin E supplementation in an HFD had an anti-inflammatory effect by decreasing IL-6 production in epididymal adipose tissue in mice and in 3T3-L1 adipocytes stimulated with LPS. Our results suggest that vitamin E and D3 supplementation can be used as an adjunctive therapy to reduce the proinflammatory cytokines present in obese patients.</p

Recuperação nutricional com farelo de arroz não modificou o balanço energético e os níveis de leptina e insulina

OBJECTIVE: To investigate the effect of nutritional recovery with rice bran on energy balance, leptin and insulin levels. METHODS: Weaned Wistar rats were fed on a 17% (Control - C) or 0.5% (Aproteic - A) protein diet for 12d. After this, rats were kept on a C diet (C) or recovered with control (Recovered Control - RC) or control plus recovered rice bran diet (Recovered Rice Bran - RRB). RESULTS: Despite the increased food intake, group A exhibited lower carcass fat associated to low serum leptin. RRB and RC groups showed lower carcass weight and energy intake and expenditure. Energy expenditure was positively associated with food intake and carcass weight. Negative correlations between HOMA-IR and energy expenditure and energy intake were observed. CONCLUSION: Nutritional recovery with rice bran did not modify energy balance, leptin and insulin levels.OBJETIVO: Investigar o efeito da recuperação nutricional com farelo de arroz sobre o balanço energético e níveis de leptina e insulina. MÉTODOS: Ratos Wistar recém-desmamados foram alimentados com 17% (Controle - C) ou 0,5% (Aproteico - A) de proteína (caseína) durante 12 dias. Em seguida, ratos permaneceram com dieta controle (C) ou foram recuperados com controle (Recuperados Controle - RC) ou controle mais 5% de farelo de arroz (Recuperados com Farelo de Arroz - RFA) durante 21 dias. RESULTADOS: Apesar de a ingestão alimentar ter sido maior em A, a gordura na carcaça foi reduzida, sendo associada com menor nível de leptina. Os grupos RFA e RC tiveram redução no peso da carcaça, no gasto e ingestão de energia. O gasto energético foi correlacionado com a ingestão de alimentos e o peso da carcaça fresco. Foi observada correlação negativa entre HOMA-IR com gasto energético e com ingestão de energia. CONCLUSÃO: A recuperação nutricional com farelo de arroz não modificou o balanço energético, nem os níveis de leptina e insulina.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de Mato Grosso Faculdade de NutriçãoUniversidade Federal de São Paulo (UNIFESP) Departamento de Fisiologia da NutriçãoUNIFESP, Depto. de Fisiologia da NutriçãoSciEL

A Identidade Europeia de Segurança e Defesa : alguns elementos sobre a evolução da posição portuguesa

A posição portuguesa é hoje claramente favorável à Identidade Europeia de Segurança e Defesa, propugnando o emprego pela UEO dos meios da NATO e apoiando o objectivo de progressiva integração da UEO na União Europeia. Esta orientação insere-se num desenvolvimento gradual da doutrina desde que Portugal aderiu à União Europeia. Nesta, Portugal tem reagido à percepção da ameaça de marginalização relativamente aos principais centros de decisão. Daí a vontade política no sentido de evitar a condenação de Portugal a um estatuto de "perifericidade". Neste contexto não é exagerado afirmar que a evolução da posição portuguesa em matéria de identidade europeia de segurança e defesa se explica basicamente pelas mesmas razões que levaram Portugal a integrar desde o início o sistema de Schengen e a aderir ao Sistema Monetário Europeu, e que hoje conduzem o governo a declarar como primeira prioridade a inclusão de Portugal no núcleo fundador do euro. Com efeito, a preocupação de Lisboa tem sido a de evitar que um qualquer "núcleo duro" venha a remeter Portugal para uma segunda divisão europeia

Hydrogenated fat intake during pregnancy and lactation caused increase in TRAF-6 and reduced AdipoR1 in white adipose tissue, but not in muscle of 21 days old offspring rats

<p>Abstract</p> <p>Background</p> <p>Although lipids transfer through placenta is very limited, modification in dietary fatty acids can lead to implications in fetal and postnatal development. <it>Trans </it>fatty acid (TFA) intake during gestation and lactation have been reported to promote dyslipidemia and increase in pro- inflammatory adipokines in offspring. The aim of this study was to evaluate whether the alterations on pro-inflammatory cytokines and dyslipidemia observed previously in 21-d-old offspring of rats fed a diet containing hydrogenated vegetable fat during gestation and lactation were related to alterations in TLR-4, TRAF-6 and adipo-R1 receptor in white adipose tissue and muscle. On the first day of gestation, rats were randomly divided into two groups: (C) received a control diet, and (T) received a diet enriched with hydrogenated vegetable fat, rich in <it>trans </it>fatty acids. The diets were maintained throughout gestation and lactation. Each mother was given eight male pups. On the 21st day of life the offspring were killed. Blood, soleus and extensor digital longus (EDL) muscles, and retroperitoneal (RET) white adipose tissue were collected.</p> <p>Results</p> <p>21-d-old of T rats had higher serum triacylglycerols, cholesterol, and insulin. The Adipo R1 protein expression was lower in RET and higher in EDL of T group than C. TLR-4 protein content in all studied tissues were similar between groups, the same was verified in TRAF-6 protein expression in soleus and EDL. However, TRAF-6 protein expression in RET was higher in T than C.</p> <p>Conclusion</p> <p>These results demonstrated that maternal ingestion of hydrogenated vegetable fat rich in TFAs during gestation and lactation decrease in Adipo R1 protein expression and increase in TRAF-6 protein expression in retroperitoneal adipose tissue, but not in skeletal muscle, which could contributed for hyperinsulinemia and dyslipidemia observed in their 21-d-old offspring.</p

Both adiponectin and interleukin-10 inhibit LPS-induced activation of the NF-kappa B pathway in 3T3-L1 adipocytes

Adiponectin and interleukin 10 (IL-10) are adipokines that are predominantly secreted by differentiated adipocytes and are involved in energy homeostasis, insulin sensitivity, and the anti-inflammatory response. These two adipokines are reduced in obese subjects, which favors increased activation of nuclear factor kappa B (NF-kappa B) and leads to elevation of pro-inflammatory adipokines. However, the effects of adiponectin and IL-10 on NF-kappa B DNA binding activity (NF-kappa Bp50 and NF-kappa Bp65) and proteins involved with the toll-like receptor (TLR-2 and TLR-4) pathway, such as MYD88 and TRAF6 expression, in lipopolysaccharide-treated 3T3-L1 adipocytes are unknown. Stimulation of lipopolysaccharide-treated 3T3-L1 adipocytes for 24 h elevated IL-6 levels; activated the NF-kappa B pathway cascade; increased protein expression of IL-6R, TLR-4, MYD88, and TRAF6; and increased the nuclear activity of NF-kappa B (p50 and p65) DNA binding. Adiponectin and IL-10 inhibited the elevation of IL-6 levels and activated NF-kappa B (p50 and p65) DNA binding. Taken together, the present results provide evidence that adiponectin and IL-10 have an important role in the anti-inflammatory response in adipocytes. in addition, inhibition of NF-kappa B signaling pathways may be an excellent strategy for the treatment of inflammation in obese individuals. (C) 2011 Elsevier B.V. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Dept Fis, BR-04023060 São Paulo, BrazilUniv São Paulo, Inst Biomed Sci, Canc & Metab Grp, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Fis, BR-04023060 São Paulo, BrazilFAPESP: 08/54733-0Web of Scienc

Lipases and lipid droplet-associated protein expression in subcutaneous white adipose tissue of cachectic patients with cancer

Background: Cancer cachexia is a multifactorial metabolic syndrome characterized by marked loss of adipose tissue and skeletal muscle. Fat loss from adipose tissue in cancer cachexia is partly the result of increased lipolysis. Despite the growing amount of studies focused on elucidating the mechanisms through which lipolysis-related proteins regulate the lipolytic process, there are scarce data concerning that profile in the adipose tissue of cancer cachectic patients. Considering its fundamental importance, it was our main purpose to characterize the expression of the lipolysis-related proteins in the white adipose tissue of cachectic cancer patients. Methods: Patients from the University Hospital were divided into three groups: control, cancer cachexia (CC), and weight-stable cancer patients (WSC). To gain greater insight into adipose tissue wasting during cancer cachexia progression, we have also analyzed an experimental model of cachexia (Walker 256 carcinosarcoma). Animals were divided into: control, intermediate cachexia (IC) and terminal cachexia (TC). Subcutaneous white adipose tissue of patients and epidydimal white adipose tissue of animals were investigated regarding molecular aspects by determining the protein content and gene expression of hormone-sensitive lipase (HSL), adipose triglyceride lipase (ATGL), comparative gene identification-58 (CGI-58), perilipin 1, leptin, adiponectin, visfatin, and tumour necrosis factor alpha (TNF-alpha). Results: We found augmented lipolysis in CC associated with increased HSL expression, as well as upregulation of ATGL expression and reduction in perilipin 1 content. In IC, there was an imbalance in the secretion of pro-and anti-inflammatory factors. The alterations at the end-stage of cachexia were even more profound, and there was a reduction in the expression of almost all proteins analyzed in the animals. Conclusions: Our findings show that cachexia induces important morphological, molecular, and humoral alterations in the white adipose tissue, which are specific to the stage of the syndrome.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Univ São Paulo, Canc Metab Res Grp, Inst Biomed Sci, Dept Surg,Fac Med, São Paulo, BrazilSão Paulo State Univ UNESP, Exercise & Immunometab Res Grp, Dept Phys Educ, Presidente Prudente, SP, BrazilUniv Fed São Paulo, UNIFESP, Dept Fisiol, São Paulo, BrazilUniv São Paulo, Univ Hosp, Dept Clin Surg, São Paulo, BrazilUniv Mogi das Cruzes, Lab Adipose Tissue Biol, Ctr Integrated Biotechnol, Mogi Das Cruzes, BrazilUniv São Paulo, Inst Biomed Sci, Ave Prof Lineu Prestes 1524,Lab 434, BR-05508900 São Paulo, SP, BrazilUniv Fed São Paulo, UNIFESP, Dept Fisiol, São Paulo, BrazilFAPESP: 2012/50079-0Web of Scienc