Luciana Pellegrini Pisani

Type of fatty acids in maternal diets during pregnancy and/or lactation and metabolic consequences of the offspring

During pregnancy and/or lactation, maternal nutrition is related to the adequate development of the fetus, newborn and future adult, likely by modifications in fetal programming and epigenetic regulation. Fetal programming is characterized by adaptive responses to specific environmental conditions during early life stages, which may alter gene expression and permanently affect the structure and function of several organs and tissues, thus influencing the susceptibility to metabolic disorders. Regarding lipid metabolism during the first two trimesters of pregnancy, the maternal body accumulates fat, whereas in late pregnancy, the lipolytic activity in the maternal adipose tissue is increased. However, an excess or deficiency of certain fatty acids may lead to adverse consequences to the fetuses and newborns. Fetal exposure to trans fatty acids appears to promote early deleterious effects in the offsprings health, thereby increasing the individual risk for developing metabolic diseases throughout life. Similarly, the maternal intake of saturated fatty acids seems to trigger alterations in the liver and adipose tissue function associated with insulin resistance and diabetes. The polyunsaturated fatty acids (PUFAs), particularly long-chain PUFAs (long-chain PUFA-arachidonic acid, eicosapentaenoic acid and docosahexaenoic acid), play an important and beneficial physiologic role in the offspring who receive this fatty acid during critical periods of development. Therefore, the maternal nutritional condition and fatty acid intake during pregnancy and/or lactation are critical factors that are strongly associated with normal fetal and postnatal development, which influence the modifications in fetal programming and in the individual risk for developing metabolic diseases throughout life.

Hydrogenated fat intake during pregnancy and lactation modifies serum lipid profile and adipokine mRNA in 21-day-old rats.

OBJECTIVE We examined 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 21-d-old offspring. METHODS Pregnant and lactating Wistar rats were fed with a control diet (C group) or one enriched with hydrogenated vegetable fat (T group). After delivery, male offspring were weighed weekly and killed at day 21 of life by decapitation. Blood and retroperitoneal, epididymal, and subcutaneous white adipose tissues were collected. RESULTS Offspring of T-group rats had increased serum triacylglycerols and cholesterol, white adipose tissue plasminogen activator inhibitor-1, and tumor necrosis factor-alpha gene expression, and carcass lipid content and decreased blood leptin and adiponectin and adiponectin gene expression. CONCLUSION Ingestion of hydrogenated vegetable fat by the mother during gestation and lactation alters the blood lipid profiles and the expression of proinflammatory adipokynes by the adipose tissue of offspring aged 21 d.

Anthocyanins as inflammatory modulators and the role of the gut microbiota

The health benefits of consuming fruits that are rich in polyphenols, especially anthocyanins, have been the focus of recent in vitro and in vivo investigations. Thus, greater attention is being directed to the reduction of the inflammatory process associated with the intestinal microbiota and the mechanism underlying these effects because the microbiota has been closely associated with the metabolism of these compounds in the gastrointestinal tract. Further interest lies in the ability of these metabolites to modulate the growth of specific intestinal bacteria. Thus, this review examines studies involving the action of the anthocyanins that are present in many fruits and their effect in the modulating the inflammatory process associated with the interaction between the host and the gut microbiota. The findings of both in vitro and in vivo studies suggest a potential antiinflammatory effect of these compounds, which seem to inhibit activation of the signaling pathway mediated by the transcription factor NFκB. This effect is associated with modulation of a beneficial gut microbiota, particularly an increase in Bifidobacterium strains.

Is the neck circumference an emergent predictor for inflammatory status in obese adults

Background:  Plasminogen Activator Inhibitor 1 (PAI‐1) is a prothrombotic adipokine involved in the coagulation cascade and fibrinolysis that associated with proinflammatory adipokines may increase the risk related to obesity. Anthropometric measures are commonly used in clinical practice and, currently, neck circumference (NC) has been used as a marker of cardiovascular risk that can favour inflammatory factors.

Fructose alters adiponectin, haptoglobin and angiotensinogen gene expression in 3T3-L1 adipocytes

Fructose- or sucrose-rich diets can cause insulin resistance and increase the risk of cardiovascular disease. Adipokines are correlated with the development of these diseases in obesity. We hypothesize that fructose and sucrose induce insulin resistance via effects on adipokine gene expression in adipocytes. This study analyzed the effect of fructose or glucose on adiponectin, haptoglobin, and angiotensinogen gene expression in 3T3-L1 adipocytes. Ten days after differentiation, the cells were pretreated with serum- and glucose-free medium. Twenty-four hours later, fructose or glucose (0, 5, 10, or 20 mmol) was added into the medium, and the cells were collected after a further 24 hours. Adiponectin, haptoglobin, and angiotensinogen gene expression were determined. Adiponectin gene expression increased when 10 or 20 mmol glucose was added compared with that observed for the non-hexose-treated cells. A similar effect occurred when 5 mmol fructose was added. Glucose (10 mmol) and fructose (20 mmol) stimulated haptoglobin gene expression in 3T3-L1 adipocytes compared with 0 mmol, with glucose producing a more pronounced effect. Although 20 mmol fructose caused an increase in angiotensinogen gene expression, glucose did not. In conclusion, in this study of 2 hexoses revealed an increase in adiponectin gene expression, suggesting that the effect of a glucose-rich diet on the development of insulin resistance is not related to the effect of these hexoses on adipocyte adiponectin gene expression. However, insulin resistance and cardiovascular disease promoted by fructose-rich diets could be partially related to the effect of fructose on adiponectin and angiotensinogen gene expression.

Jussara (Euterpe edulis Mart.) Supplementation during Pregnancy and Lactation Modulates the Gene and Protein Expression of Inflammation Biomarkers Induced by trans-Fatty Acids in the Colon of Offspring

Maternal intake of trans-fatty acids (TFAs) in the perinatal period triggers a proinflammatory state in offspring. Anthocyanins contained in fruit are promising modulators of inflammation. This study investigated the effect of Jussara supplementation in the maternal diet on the proinflammatory state of the colon in offspring exposed to perinatal TFAs. On the first day of pregnancy rats were divided into four groups: control diet (C), control diet with 0.5% Jussara supplementation (CJ), diet enriched with hydrogenated vegetable fat, rich in TFAs (T), or T diet supplemented with 0.5% Jussara (TJ) during pregnancy and lactation. We showed that Jussara supplementation in maternal diet (CJ and TJ groups) reduced carcass lipid/protein ratios, serum lipids, glucose, IL-6, TNF-α, gene expression of IL-6R, TNF-αR (P < 0.05), TLR-4 (P < 0.01), and increase Lactobacillus spp. (P < 0.05) in the colon of offspring compared to the T group. The IL-10 (P = 0.035) and IL-10/TNF-α ratio (P < 0.01) was higher in the CJ group than in the T group. The 0.5% Jussara supplementation reverses the adverse effects of perinatal TFAs, improving lipid profiles, glucose levels, body composition, and gut microbiota and reducing low-grade inflammation in the colon of 21-day-old offspring, and could contribute to reducing chronic disease development.

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

BackgroundAlthough lipids transfer through placenta is very limited, modification in dietary fatty acids can lead to implications in fetal and postnatal development. Trans 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 trans 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.Results21-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.ConclusionThese 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.

Fatty-acid-mediated hypothalamic inflammation and epigenetic programming

A high-fat diet is the main environmental cue that has been studied in the hypothalamus since the discovery of its connection with hypothalamic inflammation. Current evidence shows hypothalamic inflammation as a likely mechanism for the dysregulation on the homeostatic control of energy balance, which leads to metabolic alterations and obesity. Although this mechanism seems to be reversible when set during adulthood, we argue whether dietary fatty acids, during critical periods of development, could affect hypothalamic function permanently and set an increased susceptibility to obesity. We found few experimental studies that looked at programming induced by different fatty acids on the hypothalamus. They clearly showed a connection between maternal fat diet, hypothalamic inflammation and metabolic alterations in the offspring. We found that not only a high-fat diet but also a normolipidic diet with unbalanced quantities of different fatty acids produced diverse inflammatory responses on the hypothalamus. Therefore, strategies of manipulating dietary fatty acids in pregnant and lactating women may have great impact on the populations future health. However, more research is still needed on the effects of fatty acids and the hypothalamic inflammation on programming.

The Role of Leptinemia State as a Mediator of Inflammation in Obese Adults

Hyperleptinemia has emerged as a marker of proinflammatory status, while the adiponectin/leptin ratio has been used to identify anti-inflammatory state. In this context, the aims of the present study were to investigate the role of leptinemia, adjusted by tertiles, on inflammatory state in obese adults according to obesity degree. This is a cross-sectional study comprised of 43 obese adults. The anthropometric variables and body composition were analyzed, as well as markers of inflammation such as leptin, adiponectin, and plasminogen activator inhibitor. Subjects were grouped using adjusted tertiles of the leptin levels. The major finding was the negative correlation between leptin concentration with adiponectin/leptin ratio (r=-0.622, p=0.000) and the positive correlation with leptin/adiponectin ratio (r=0.622, p=0.000). Indeed, both ratios were decreased and increased, respectively, according to the obesity degree. Furthermore, in the stepwise multiple linear regression analysis, the high degree of obesity was an independent predictor of leptinemia when adjusted for age and BMI (β=0.588, p=0.000 and β=0.778, p=0.005). Finally, the strong negatively correlation between the leptinemia with adiponectin/leptin ratio and the positive correlation with leptin/adiponectin ratio reinforce the role of this adipokine as a biomarker of inflammation in obese adults, according to obesity degree. Our findings can elucidate that hyperleptinemic status was a major factor in the proinflammatory status related to higher obesity degree. All together, these data reinforce the role of leptinemia state as a mediator of inflammation in obese adults.

Oligofructose supplementation (10%) during pregnancy and lactation does not change the inflammatory effect of concurrent trans fatty acid ingestion on 21-day-old offspring

BackgroundPreviously, we demonstrated that trans fatty acid ingestion during pregnancy and lactation caused a pro-inflammatory effect on the newborn. The opposite effect was described for gestational prebiotic intake. In the present study, we examined whether supplementation of the diet of the dams with 10% of oligofructose with or without hydrogenated vegetable fat during pregnancy and lactation affected the pro-inflammatory status on the pups at age 21 days.MethodsOn the first day of pregnancy, rats were divided into four groups, each of which received one of four diets: a control diet (C group), a control diet supplemented with 10% oligofructose (CF group), a diet enriched with hydrogenated vegetable fat containing trans fatty acids (T group) or a diet enriched with hydrogenated vegetable fat containing trans fatty acids supplemented with 10% oligofructose (TF group). The pups were weighed at birth and at 7, 14 and 21 days of life and were euthanized on post-natal day 21. The serum glucose, insulin and adiponectin concentrations were analyzed. The IL-6, IL-10 and TNF-α contents of the retroperitoneal white adipose tissue, liver, soleus and extensor digital longus muscles were analyzed by ELISA. The results are presented as the means ± standard error of the mean. Statistical significance was assessed using two-way ANOVA, followed by Tukeys test and considered significant at p < 0.05ResultsThe body weights of the 21-day old pups in the CF and TF groups were significant lower than those of the C (27% and 21%) and T (25% and 19%, respectively) groups. The serum levels of adiponectin in the CF, T and TF groups were lower than in the C group (41%; 34% and 31%, respectively). In the retroperitoneal adipose tissue, the IL-6 content was increased in TF group relative to the C and CF groups (74% for both), and the TNF-α content was higher in the T and TF groups than in the C group (62% and 98%, respectively). In the liver, the TNF-α (56% and 104%) and IL-10 (52% and 73%) contents were increased in the CF group relative to the C and TF groups.ConclusionsSupplementation of the diet of the dams with 10% of oligofructose during pregnancy and lactation, independent of supplementation with hydrogenated vegetable fat, adversely affected the development of the offspring and contributed to development of a pro-inflammatory status in the pups on postnatal day 21.