Hepatic Epigenetic Reprogramming After Liver Resection in Offspring Alleviates the Effects of Maternal Obesity.

Obesity has become a public health problem in recent decades, and during pregnancy, it can lead to an increased risk of gestational complications and permanent changes in the offspring resulting from a process known as metabolic programming. The offspring of obese dams are at increased risk of developing non-alcoholic fatty liver disease (NAFLD), even in the absence of high-fat diet consumption. NAFLD is a chronic fatty liver disease that can progress to extremely severe conditions that require surgical intervention with the removal of the injured tissue. Liver regeneration is necessary to preserve organ function. A range of pathways is activated in the liver regeneration process, including the Hippo, TGFß, and AMPK signaling pathways that are under epigenetic control. We investigated whether microRNA modulation in the liver of the offspring of obese dams would impact gene expression of Hippo, TGFß, and AMPK pathways and tissue regeneration after partial hepatectomy (PHx). Female Swiss mice fed a standard chow or a high-fat diet (HFD) before and during pregnancy and lactation were mated with male control mice. The offspring from control (CT-O) and obese (HF-O) dams weaned to standard chow diet until day 56 were submitted to PHx surgery. Prior to the surgery, HF-O presented alterations in miR-122, miR-370, and Let-7a expression in the liver compared to CT-O, as previously shown, as well as in its target genes involved in liver regeneration. However, after the PHx (4 h or 48 h post-surgery), differences in gene expression between CT-O and HF-O were suppressed, as well as in microRNA expression in the liver. Furthermore, both CT-O and HF-O presented a similar regenerative capacity of the liver within 48 h after PHx. Our results suggest that survival and regenerative mechanisms induced by the partial hepatectomy may overcome the epigenetic changes in the liver of offspring programmed by maternal obesity.

Maternal high-fat diet consumption programs male offspring to mitigate complications in liver regeneration.

In the last decades, obesity and nonalcoholic fatty liver disease (NAFLD) have become increasingly prevalent in wide world. Fatty liver can be detrimental to liver regeneration (LR) and offspring of obese dams (HFD-O) are susceptible to NAFLD development. Here we evaluated LR capacity in HFD-O after partial hepatectomy (PHx). HFD-O re-exposed or not to HFD in later life were evaluated for metabolic parameters, inflammation, proliferation, tissue repair markers and survival rate after PHx. Increasing adiposity and fatty liver were observed in HFD-O. Despite lower IL-6 levels, Ki67 labeling, cells in S phase and Ciclin D1/PCNA protein content, a lower impact on survival rate was found after PHx, even when re-exposed to HFD. However, no difference was observed between offspring of control dams (SC-O) and HFD-O after surgery. Although LR impairment is dependent of steatosis development, offspring of obese dams are programmed to be protected from the damage promoted by HFD.

MicroRNA Let-7 targets AMPK and impairs hepatic lipid metabolism in offspring of maternal obese pregnancies.

Nutritional status during gestation may lead to a phenomenon known as metabolic programming, which can be triggered by epigenetic mechanisms. The Let-7 family of microRNAs were one of the first to be discovered, and are closely related to metabolic processes. Bioinformatic analysis revealed that Prkaa2, the gene that encodes AMPK α2, is a predicted target of Let-7. Here we aimed to investigate whether Let-7 has a role in AMPKα2 levels in the NAFLD development in the offspring programmed by maternal obesity. Let-7 levels were upregulated in the liver of newborn mice from obese dams, while the levels of Prkaa2 were downregulated. Let-7 levels strongly correlated with serum glucose, insulin and NEFA, and in vitro treatment of AML12 with glucose and NEFA lead to higher Let-7 expression. Transfection of Let-7a mimic lead to downregulation of AMPKα2 levels, while the transfection with Let-7a inhibitor impaired both NEFA-mediated reduction of Prkaa2 levels and the fat accumulation driven by NEFA. The transfection of Let-7a inhibitor in ex-vivo liver slices from the offspring of obese dams restored phospho-AMPKα2 levels. In summary, Let-7a appears to regulate hepatic AMPKα2 protein levels and lead to the early hepatic metabolic disturbances in the offspring of obese dams.

Lipid overload during gestation and lactation can independently alter lipid homeostasis in offspring and promote metabolic impairment after new challenge to high-fat diet.

BACKGROUND: Nutritional status in early life is critically involved in the metabolic phenotype of offspring. However the changes triggered by maternal consumption of high-fat diet (HFD) in pre- or postnatal period should be better understood. Here we evaluated whether maternal HFD consumption during gestation and lactation could differently affect liver miR-122 and miR-370 expression leading to metabolic damages observed in offspring. Moreover, we investigate whether early overnutrition program offspring to more harmful response to HFD in later life. METHODS: Female mice were fed either a standard chow (SC) diet or a HFD three weeks before and during mating, gestation and/or lactation. Offspring were evaluated on the delivery day (d0), in a cross-fostering model at day 28 (d28) and in adult life, after a re-challenge with a HFD (d82). RESULTS: In vitro analysis using liver cell line showed that palmitate could induced decrease in miR-122 and increase in miR-370 expression. Newborn pups (d0) from obese dams showed a decrease in lipid oxidation markers (Cpt1a and Acadvl), an increase in triacylglycerol synthesis markers (Agpat and Gpam), as well as lower miR-122 and higher miR-370 hepatic content that was inversely correlated to maternal serum NEFA and TAG. Pups fostered to SC dams presented an increase in body weight and Agpat/Gpam expression at d28 compared to pups fostered to HFD dams and an inverse correlation was observed between miR-122 hepatic expression and offspring serum TAG. In adult life (d82), the reintroduction of HFD resulted in higher body weight gain and hepatic lipid content. These effects were accompanied by impairment in lipid and glucose metabolism, demonstrated by reduced Cpt1a/Acadvl and increased Agpat/Gpam expression, lower glucose tolerance and insulin sensitivity. CONCLUSION: Our data suggest that both gestational and lactation overnutrition results in metabolic changes that can permanently alter lipid homeostasis in offspring. The presence of fatty acids in maternal blood and milk seem to be responsible for modulating the expression of miR-122 and miR-370, which are involved in liver metabolism. These alterations significantly increase susceptibility to obesity and ectopic lipid accumulation and lead to a more harmful response to HFD in offspring.

Assessment of plant development, morphology and flavonoid content in different cultivation treatments of Calendula officinalis L: , Asteraceae

O objetivo deste estudo foi avaliar a influência dos tratos culturais no desenvolvimento vegetal, morfologia e teor de flavonóides para Calendula officinalis L., Asteraceae. Os tratos culturais foram: calagem (CA), calagem + adubação orgânica (CAO) e calagem + adubação química NPK (CAQ). O experimento foi inteiramente casualizado com sessenta repetições e a comparação das médias realizada por ANOVA e teste de Duncan (significância de 95 por cento). Os resultados apontam que CAO e CAQ apresentaram maior desenvolvimento vegetal comparados com tratamento CA. O tratamento CAO produziu ainda, plantas com maior homogeneidade, massa fresca e número de capítulos florais por planta, mas menor biomassa de flores produzidas por cada indivíduo. Observou-se também, variações morfoanatômicas com flores tubulares com centro amarelado (TCA) e tubulares com centro acastanhado (TAC) que produziram maior teor de flavonóides (1,41 e 1,44 por cento respectivamente) comparadas com flores ligulares com centro amarelado (LCA) e ligulares com centro acastanhado (LAC) (0,89 e 0,95 por cento respectivamente). Os compostos químicos nas flores de calêndula, visualizados por cromatografia em camada delgada, demonstraram que os tratamentos não têm influencia sobre o perfil químico qualitativo do vegetal. Entretanto, cultivares de calêndula submetidas ao tratamento CAQ produziram maior quantidade de flavonóides totais (1,14 por cento) contra 1,04 por cento do CAO e 1,03 por cento de CA.

The objective of this study was to examine the influence of cultivation treatments on plant development, morphology and flavonoid content in Calendula officinalis L., Asteraceae. The cultivation treatments were liming (LIM), liming + organic fertilizer (LORG) and liming + NPK chemical fertilizer (LCHEM). The experiment was completely randomized with sixty repetitions and the means were compared by ANOVA and Duncan's test (significance of 95 percent). The results show that LORG and LCHEM produced greater plant development compared with LIM treatment. The LORG treatment also produced plants with greater homogeneity, fresh mass, and higher numbers of flowers per plant, but lower biomass of flower produced by each individual. Morphoanatomical variations were also observed with tubular flowers with yellow centres (TCA) and tubular flowers with brown centres (TAC) that produced a higher content of flavonoids (1.41 and 1.44 percent respectively), compared with ligulate flowers with yellow centres (LCA) and ligulate flowers with brown centres (LAC) (0.89 and 0.95 percent respectively). The chemical compounds in the flowers of calendula viewed by thin-layer chromatography showed that the treatments did not have any influence on the qualitative chemical profile of the plant. However, cultivars of calendula that underwent treatment LCHEM produced a greater quantity of total flavonoids (1.14 percent) against 1.04 percent for LORG and 1.03 percent for LIM.

Uptake of breast cancer screening measures among immigrant and Swiss women in Switzerland.

BACKGROUND: Early detection of breast cancer plays a crucial role in survival, and in most developed countries immigrant women present for treatment at a later stage of the disease. Compared to the indigenous population, immigrant women have a lower uptake of breast cancer prevention services. The situation for immigrant women in Switzerland is compounded by the fact that all women living in Switzerland are at major risk of developing breast cancer during their lifetime. QUESTION UNDER STUDY: Our study aimed to detect disparities in uptake of preventive methods such as mammography, clinical breast examination (CBE) and breast self-examination (BSE) among women from the four major immigrant groups Italy, Spain, former Yugoslavia and Portugal, compared to the native population in Switzerland. METHODS: This study is a secondary analysis of data from the 2002 Swiss Health Survey, a nationwide cross-sectional telephone survey. The self-reported questionnaires addressed immigrant and Swiss women of age 20 and over (n = 9,790). Descriptive statistics were used to describe the demographic characteristics of the sample. The dichotomous variables of interest, mammography, CBE and BSE were adjusted for nationality and further sociodemographic factors using logistic regression, with Swiss women serving as the comparison group. RESULTS: Main predictors for mammography uptake were higher income and older age. For the use of CBE, lower age, higher income and nationality were the strongest predictors. Women from former Yugoslavia (OR = 2.6) and Portugal (OR = 2.8) more frequently stated that they did not receive CBE compared to Swiss females (p = .011). BSE is linked to a higher socioprofessional status and to nationality. Women from Italy (OR = 1.62) and former Yugoslavia (OR = 2.6) perform BSE significantly less often than Swiss women (p = .0001). CONCLUSION: Differences exist in the use of mammography, CBE and BSE among the four major foreign nationality groups living in Switzerland compared to Swiss nationals. Immigrant and low-income women might draw benefit from a systematic and culturally adapted breast cancer screening programme to overcome disparities in access to screening.