Débora Estadella

Lipotoxicity: Effects of Dietary Saturated and Transfatty Acids

The ingestion of excessive amounts of saturated fatty acids (SFAs) and transfatty acids (TFAs) is considered to be a risk factor for cardiovascular diseases, insulin resistance, dyslipidemia, and obesity. The focus of this paper was to elucidate the influence of dietary SFA and TFA intake on the promotion of lipotoxicity to the liver and cardiovascular, endothelial, and gut microbiota systems, as well as on insulin resistance and endoplasmic reticulum stress. The saturated and transfatty acids favor a proinflammatory state leading to insulin resistance. These fatty acids can be involved in several inflammatory pathways, contributing to disease progression in chronic inflammation, autoimmunity, allergy, cancer, atherosclerosis, hypertension, and heart hypertrophy as well as other metabolic and degenerative diseases. As a consequence, lipotoxicity may occur in several target organs by direct effects, represented by inflammation pathways, and through indirect effects, including an important alteration in the gut microbiota associated with endotoxemia. Interactions between these pathways may perpetuate a feedback process that exacerbates an inflammatory state. The importance of lifestyle modification, including an improved diet, is recommended as a strategy for treatment of these diseases.

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.

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.

A palatable hyperlipidic diet causes obesity and affects brain glucose metabolism in rats

BackgroundWe have previously shown that either the continuous intake of a palatable hyperlipidic diet (H) or the alternation of chow (C) and an H diet (CH regimen) induced obesity in rats. Here, we investigated whether the time of the start and duration of these feeding regimens are relevant and whether they affect brain glucose metabolism.MethodsMale Wistar rats received C, H, or CH diets during various periods of their life spans: days 30-60, days 30-90, or days 60-90. Experiments were performed the 60th or the 90th day of life. Rats were killed by decapitation. The glucose, insulin, leptin plasma concentration, and lipid content of the carcasses were determined. The brain was sliced and incubated with or without insulin for the analysis of glucose uptake, oxidation, and the conversion of [1-14C]-glucose to lipids.ResultsThe relative carcass lipid content increased in all of the H and CH groups, and the H30-60 and H30-90 groups had the highest levels. Groups H30-60, H30-90, CH30-60, and CH30-90 exhibited a higher serum glucose level. Serum leptin increased in all H groups and in the CH60-90 and CH30-90 groups. Serum insulin was elevated in the H30-60, H60-90, CH60-90, CH30-90 groups. Basal brain glucose consumption and hypothalamic insulin receptor density were lower only in the CH30-60 group. The rate of brain lipogenesis was increased in the H30-90 and CH30-90 groups.ConclusionThese findings indicate that both H and CH diet regimens increased body adiposity independent treatment and the age at which treatment was started, whereas these diets caused hyperglycemia and affected brain metabolism when started at an early age.

Effects of a Diet Enriched with Polyunsaturated, Saturated, or Trans Fatty Acids on Cytokine Content in the Liver, White Adipose Tissue, and Skeletal Muscle of Adult Mice

This study analyzed the effect of diet enriched with 30% lipids on cytokines content in different tissues. Swiss male mice were distributed into four groups treated for 8 weeks with control (C, normolipidic diet); soybean oil (S); lard (L); and hydrogenated vegetable fat (H). We observed an increase in carcass fat in groups S and L, and the total amount of fatty deposits was only higher in group L compared with C group. The serum levels of free fatty acids were lower in the L group, and insulin, adiponectin, lipid profile, and glucose levels were similar among the groups. IL-10 was lower in group L in mesenteric and retroperitoneal adipose tissues. H reduced IL-10 only in retroperitoneal adipose tissue. There was an increase in IL-6 in the gastrocnemius muscle of the L group, and a positive correlation between TNF-α and IL-10 was observed in the livers of groups C, L, and H and in the muscles of all groups studied. The results suggested relationships between the quantity and quality of lipids ingested with adiposity, the concentration of free fatty acids, and cytokine production in white adipose tissue, gastrocnemius muscle, and liver.

Nonalcoholic Fatty Liver Disease (NAFLD), a Manifestation of the Metabolic Syndrome: New Perspectives on the Nutritional Therapy

Nonalcoholic fatty liver disease (NAFLD) is a multifactorial hepatic disease that develops through complex mechanisms that may be strongly influenced by dietary composition. NAFLD treatment is based on multidisciplinary intervention, which includes nutritional aspects. The objective of this review was to elucidate the influence and role of dietary composition, including fatty acid types, antioxidant nutrients, pre and probiotics and vitamin D in the nutritional treatment and prevention of NAFLD. Increased intake of Monounsaturated fatty acids (MUFAs) and omega-3 polyunsaturated fatty acid (PUFA), particularly as replacements for saturated fat and in a higher proportion than carbohydrates, is beneficial to NAFLD patients, improving insulin resistance; increasing plasma levels of adiponectin and its synthesis by the adipose tissue; and restoring the expression of hepatic peroxisome proliferator-activated receptor alpha (PPAR-I±), which in turn reduces cholesterol levels and triacylglycerol accumulation. n-3 PUFAs can reduce lipotoxicity caused by excessive saturated and trans fatty acid ingestion and exert a protective role in inflammatory pathways, promoting resolvins and protectins. Several mechanisms linking gut flora to NAFLD have been proposed, such as inflammation and energy extraction. Studies are often designed to explore the beneficial effects of probiotics, prebiotics and vitamin D in these pathways. The results of this review reveal that the strong positive influence bioactive compounds have on these inflammatory processes must be considered when developing treatment and prevention plans for NAFLD patients.

Proteomic profiling of the rat hypothalamus

BackgroundThe hypothalamus plays a pivotal role in numerous mechanisms highly relevant to the maintenance of body homeostasis, such as the control of food intake and energy expenditure. Impairment of these mechanisms has been associated with the metabolic disturbances involved in the pathogenesis of obesity. Since rodent species constitute important models for metabolism studies and the rat hypothalamus is poorly characterized by proteomic strategies, we performed experiments aimed at constructing a two-dimensional gel electrophoresis (2-DE) profile of rat hypothalamus proteins.ResultsAs a first step, we established the best conditions for tissue collection and protein extraction, quantification and separation. The extraction buffer composition selected for proteome characterization of rat hypothalamus was urea 7 M, thiourea 2 M, CHAPS 4%, Triton X-100 0.5%, followed by a precipitation step with chloroform/methanol. Two-dimensional (2-D) gels of hypothalamic extracts from four-month-old rats were analyzed; the protein spots were digested and identified by using tandem mass spectrometry and database query using the protein search engine MASCOT. Eighty-six hypothalamic proteins were identified, the majority of which were classified as participating in metabolic processes, consistent with the finding of a large number of proteins with catalytic activity. Genes encoding proteins identified in this study have been related to obesity development.ConclusionThe present results indicate that the 2-DE technique will be useful for nutritional studies focusing on hypothalamic proteins. The data presented herein will serve as a reference database for studies testing the effects of dietary manipulations on hypothalamic proteome. We trust that these experiments will lead to important knowledge on protein targets of nutritional variables potentially able to affect the complex central nervous system control of energy homeostasis.

Lateral hypothalamic serotonin is not stimulated during central leptin hypophagia.

Whether leptin targets the hypothalamic serotonergic system to inhibit food intake is not established. We examined the effect of a short-term i.c.v. leptin treatment on serotonin microdialysate levels in rat lateral hypothalamus. Adipose tissue gene expression was also evaluated. Male rats received four daily injections of leptin (5 μg) or vehicle (with pair-feeding to leptin-induced intake) and a fifth injection during collection of LH microdialysates. We found that serotonin and 5-HIAA levels were not affected by the leptin pre-treatment, as basal levels were similar between the leptin and the pair-fed group. These levels remained unaltered after the acute leptin injection. For gene expression studies, rats were pre-treated with five daily injections of either leptin (5 μg) or vehicle (with either pair-feeding or ad libitum intake). mRNA levels of resistin, adiponectin, lipoprotein lipase, and PPAR-gamma were unaltered by either leptin or pair-feeding. Leptin gene expression was significantly reduced by leptin but not by pair-feeding, in both the retroperitoneal (-74%) and the epididymal (-99%) depots while no differences were observed in the subcutaneous depot. The observations confirmed the absence of an acute stimulatory effect of central leptin on serotonin release in the lateral hypothalamus and showed that the pre-treatment with leptin failed to modify this pattern. This indicates that components of the serotonergic system are probably not directly affected by leptin. Additionally, the central effect of leptin was able to downregulate its own adipose tissue gene expression in a depot-specific manner while other adipokine genes were not affected.

Role of vitamin D in pregnancy and Toll-like receptor pathway

HighlightsVitamin D deficiency may exacerbate inflammation.Vitamin D regulates cell‐signaling pathways altering cytokine secretion.Vitamin D decreases LPS‐induced inflammation reducing NF‐&kgr;B expression.Early activation of the proinflammatory pathway plays a critical role in labor. Abstract There is a growing concern about the impacts of hypovitaminosis D on the health of pregnant woman, fetal development, childhood, and adult life. Variations in maternal nutrition during gestation and/or lactation play a critical role in the physiological and metabolic development of the fetus and neonate, which can induce phenotypic changes and trigger important consequences throughout life, such as type 2 diabetes, cardiovascular disease, obesity, and hypertension. Vitamin D plays a role in regulating cell proliferation and differentiation and in modulating the innate and adaptive immune response. Also, vitamin D correlates with changes in cytokines, anti and proinflammatory, as well as prevents inflammation induced by changes in myometrial cells mediated by the nuclear factor kappa B pathway. Further investigation is required regarding these relationship.

Serum myristic fatty acid negatively correlates with anti-inflammatory adiponectin/leptin ratio in obese adolescents: effects of long- term therapy

Obesity is related to metabolic disorders partially mediated by inflammatory state. In this way, adiponectin/leptin ratio is considered an anti-inflammatory biomarker related to cardiovascular risks. Evidence suggest that decrease in saturated fatty acid intake is an important dietary recommendation to reduce cardiovascular risk factors. Thus, the purpose of the present study was to evaluate if serum myristic fatty acid can modulate metabolic profile and inflammatory process in obese adolescents after weight-loss therapy. Twenty-nine obese post-pubertal obese adolescents, aged 14 to 19 years, were submitted to the long-term interdisciplinary treatment, including physical exercise, clinic, nutritional and psychological intervention. The blood samples were collected to glycaemia, insulin, lipid profile, leptin and adiponectin analysis. Serum fatty acid composition was performed by technical of chromatography in fizzy phase. The therapy promoted significant improvement in body mass, BMI, subcutaneous and visceral fat, insulin, lipid profile, leptin and leptin/adiponectin ratio. Significant decrease in myristic fatty acid was observed. Simple linear regression analysis showed that myristic fatty acid was positively associated with changes in triglycerides and very low density lipoprotein cholesterol, and was negatively associated with adiponectin/leptin ratio. In summary, we observed that long-term weight loss therapy was effective to improve metabolic/inflammatory profile and serum myristic fatty acid. Moreover, our results suggested the relation between changes in serum myristic fatty acids with the anti-inflammatory adiponectin/ leptin ratio, which may modulate metabolic and inflammatory process related to obesity.