Structuration of lipid bases zero-trans and palm oil-free for food applications.

This work evaluated structured lipids (SLs) through chemical and enzymatic interesterification (CSLs and ESLs). Blends of soybean oil and peanut oil 1:1 wt% were used, with gradual addition of fully hydrogenated crambe to obtain a final behenic acid concentration of 6, 12, 18, and 24 %. Chemical catalysis used sodium methoxide (0.4 wt%) at 100 °C for 30 min, while enzymatic catalysis used Lipozyme TL IM (5 wt%) at 60 °C for 6 h. Major fatty acids identified were C16:0, C18:0, and C22:0. It was observed that with gradual increase of hard fat, the CSLs showed high concentrations of reaction intermediates, indicating further a steric hindrance, unlike ESLs. Increased hard fat also altered crystallization profile and triacylglycerols composition and ESLs showed lower solid fat, unlike CSLs. Both methods effectively produced SLs as an alternative to trans and palm fats, view to potential future applications in food products.

Enzymatic production process of capric acid-rich structured lipids: Development of formulation as a new therapeutic approach.

The present work reports an optimization of the synthesis of MLM-type (medium, long, medium) structured lipids (SL) through an acidolysis reaction of grape seed oil with capric acid catalyzed by Rhizopus oryzae lipase immobilized. At first, tests were carried out by preparing the biocatalysts using enzyme loadings (0.15 to 1 g of enzymatic powder) for each gram of support. Enzyme loading was used 0.3 g of enzymatic powder, and hydrolytic activity of 1860 ± 23.4 IU/g was reached. Optimized conditions determined by the Central Composite Rotatable Design (CCRD) revealed that the acidolysis reaction reached approximately 59 % incorporation degree (%ID) after 24 h, in addition to the fact that the biocatalyst could maintain the incorporation degree in five consecutive cycles. From this high incorporation degree, cell viability assays were performed with murine fibroblast cell lines and human cervical adenocarcinoma cell lines. Concerning the cytotoxicity assays, the concentration of MLM-SL to 1.75 and 2 % v/v were able to induce cell death in 56 % and 64 % of adenocarcinoma cells, respectively. Human cervical adenocarcinoma cells showed greater sensitivity to the induction of cell death when using emulsions with MLM-SL > 1.75 % v/v compared to emulsions with lower content indicating a potential for combating carcinogenic cells.

Solvent-Free Enzymatic Synthesis of Dietary Triacylglycerols from Cottonseed Oil in a Fluidized Bed Reactor.

The synthesis of structured lipids with nutraceutical applications, such as medium-long-medium (MLM) triacylglycerols, via modification of oils and fats represents a challenge for the food industry. This study aimed to synthesize MLM-type dietary triacylglycerols by enzymatic acidolysis of cottonseed oil and capric acid (C10) catalyzed by Lipozyme RM IM (lipase from Rhizomucor miehei) in a fluidized bed reactor (FBR). After chemical characterization of the feedstock and hydrodynamic characterization of the reactor, a 22 central composite rotatable design was used to optimize capric acid incorporation. The independent variables were cycle number (20-70) and cottonseed oil/capric acid molar ratio (1:2-1:4). The temperature was set at 45 °C. The best conditions, namely a 1:4 oil/acid molar ratio and 80 cycles (17.34 h), provided a degree of incorporation of about 40 mol%, as shown by compositional analysis of the modified oil. Lipozyme RM IM showed good operational stability (kd = 2.72 × 10-4 h-1, t1/2 = 2545.78 h), confirming the good reuse capacity of the enzyme in the acidolysis of cottonseed oil with capric acid. It is concluded that an FBR configuration is a promising alternative for the enzymatic synthesis of MLM triacylglycerols.

Recent Advances in the Microencapsulation of Essential Oils, Lipids, and Compound Lipids through Spray Drying: A Review.

In recent decades, the microcapsules of lipids, compound lipids, and essential oils, have found numerous potential practical applications in food, textiles, agricultural products, as well as pharmaceuticals. This article discusses the encapsulation of fat-soluble vitamins, essential oils, polyunsaturated fatty acids, and structured lipids. Consequently, the compiled information establishes the criteria to better select encapsulating agents as well as combinations of encapsulating agents best suited to the types of active ingredient to be encapsulated. This review shows a trend towards applications in food and pharmacology as well as the increase in research related to microencapsulation by the spray drying of vitamins A and E, as well as fish oil, thanks to its contribution of omega 3 and omega 6. There is also an increase in articles in which spray drying is combined with other encapsulation techniques, or modifications to the conventional spray drying system.

Potencial quimiopreventivo de lipídios estruturados obtidos da Tributirina e Tricaprilina na fase de promoção da hepatocarcinogênese experimental / Chemopreventive potential of structured lipids obtained from Tributyrin and Tricaprylin in the promotion phase of experimental hepatocarcinogenesis

A quimioprevenção do câncer refere-se ao uso de compostos naturais ou sintéticos para prevenir o desenvolvimento das neoplasias antes do estabelecimento da malignidade. O ácido butirico (AB) atua como um potente quimiopreventivo na hepatocarcinogênese, reduzindo o número e o tamanho de lesões pré neoplásicas persistentes (pLPN), induzindo a apoptose e modulando mecanismos epigenéticos. Já o ácido caprílico (AC), além da sua atuação como potencializador de absorção, vem sendo investigado na área da prevenção do câncer. Neste cenário, o objetivo do trabalho visa avaliar a atividade quimiopreventiva de lipídios estruturados (EST) obtidos por interesterificação enzimática da tributirina com a tricaprilina, na fase de promoção da hepatocarcinogênese experimental. Após o processo de interesterificação, o produto final apresentou novos triacilgliceróis com composição de duas moléculas de ácido butírico para uma de ácido caprilíco. Ratos machos isogênicos da linhagem Fischer 344 foram submetidos ao modelo do hepatócito resistente, sendo distribuídos em dois grupos e tratados diariamente por via intragástrica com lipídios estruturados (EST) ou com o seu controle isocalórico, a maltodextrina (MD), durante a fase de promoção. Como esperado, não houve diferença estatística (p>0,05) em relação ao peso inicial e final dos animais dos grupos MD e EST, o que indica ausência de toxicidade dos compostos administrados. Na análise macroscópica do fígado, foi observada uma redução de 33,3% no grupo EST em relação ao número médio de nódulos macroscópicos em comparação ao grupo MD, porém essa redução não atingiu diferença estatística (p>0,05). Para a avaliação das lesões pré neoplásicas (LPN) foi utilizada a marcação imunoistoquímica para glutationa-S-transferase (GST-P). O grupo EST apresentou uma redução no número de lesões em remodelação e total GSTP-P+, quando comparado com o grupo MD (p<0,05). Quando avaliada a % de corpúsculos apoptóticos e índice de proliferação celular, não houve diferença estatística entre os grupos (p>0,05). Animais tratados com lipídios estruturados apresentaram maiores (p<0,05) concentrações de AC e AB por grama de tecido hepático em relação ao tratamento com maltodextrina. Em relação aos danos no DNA, o grupo EST resultou em cometas de comprimentos menores (p<0,05), menores níveis de γ-H2AX (p<0,05) e maiores concentrações de p53 nuclear, quando comparados aos animais que receberam maltodextrina, sugerindo uma proteção contra danos no DNA no grupo tratado com EST. Os resultados mostraram que o tratamento com EST resultou em ações efetivas na fase de promoção da hepatocarcinogênese experimental

Cancer chemoprevention refers to the use of natural or synthetic compounds to prevent the development of neoplasms before the establishment of malignancy. Butyric acid (AB) acts as a potent chemopreventive in hepatocarcinogenesis, reducing the number and size of persistent preneoplastic lesions (pLPN), inducing apoptosis and modulating epigenetic mechanisms. Caprylic acid (CA), in addition to its role as an absorption enhancer, has been investigated in the area of cancer prevention. In this scenario, the objective of this work was to evaluate the chemopreventive activity of structured lipids (EST) obtained by enzymatic interesterification of tributyrin with tricaprylin, in the phase of promotion experimental hepatocarcinogenesis. After the interesterification process, the final product presented new triacylglycerols with a composition of two molecules of butyric acid to one of caprylic acid. Isogenic male Fischer 344 rats were submitted to the resistant hepatocyte model, divided into two groups and treated daily intragastrically with structured lipids (EST) or with its isocaloric control, maltodextrin (MD), during the promotion phase. As expected, there was no statistical difference (p>0.05) in relation to the initial and final weight of the animals in the MD and EST groups, which indicates the absence of toxicity of the administered compounds. In the macroscopic analysis of the liver, a reduction of 33.3% was observed in the EST group in relation to the mean number of macroscopic nodules compared to the MD group, but this reduction did not reach a statistical difference (p>0.05). For the evaluation of pre-neoplastic lesions (PNL) immunohistochemical staining for glutathione-Stransferase (GST-P) was used. The EST group showed a reduction in the number of remodeling lesions and total GSTP-P+, when compared to the MD group (p<0.05). Animals treated with structured lipids had higher (p<0.05) concentrations of AC and AB per gram of liver tissue compared to treatment with maltodextrin. Regarding DNA damage, the EST group resulted in comets of shorter lengths (p<0.05), lower levels of γ-H2AX (p<0.05) and high concentration of nuclear p53, when compared to animals that received maltodextrin, suggesting protection against DNA damage in the EST treated group. The results showed that EST treatment resulted in effective actions in the promotion phase of experimental hepatocarcinogenesis

Enzymatic synthesis of structured lipids from grape seed (Vitis vinifera L.) oil in associated packed bed reactors.

Triacylglycerols (TAGs) can be modified to increase the absorption of fatty acids, prevent obesity, and treat fat malabsorption disorders and metabolic diseases. Medium-long-medium (MLM)-type TAGs, which contain medium-chain fatty acids in the sn-1 and sn-3 positions of the glycerol backbone and a long-chain fatty acid in the sn-2 position, show particularly interesting nutritional characteristics. This study aimed to synthesize MLM-type TAGs by enzymatic acidolysis of grape seed oil with medium-chain capric acid (C10:0) in associated packed bed reactors. The reaction was carried out during 120 H, at 45 °C, using lipase from Rhizomucor miehei (Lipozyme® RM IM). The residence time distribution of reagents in the reactor was quantified to evaluate the reactor behavior and to diagnose the existence of preferential paths. The reaction progress was monitored by analyzing TAG composition and, at the steady state (after 48 H of reaction), the incorporation degree achieved a value of 39.91 ± 2.77%. To enhance the capric acid incorporation, an acidolysis reaction in associated packed bed reactors was performed. The results showed a good operational stability of the biocatalyst, revealing values of half-life 209.64 H, 235.63 H of packed bed and associated packed bed reactor, respectively, and a deactivation coefficient 0.0061 H-1 .

Evaluation of Nanostructured Lipid Carriers Produced with Interesterified Buriti Oil.

RESEARCH BACKGROUND: Extracted from the pulp of an Amazonian fruit, buriti oil is rich in micronutrients with antioxidant properties and high biological value. The few studies available indicate that this oil could be used in a wide range of applications; however, there are no studies that work on the improvement in the characteristics of this oil for commercial application. The enzymatic interesterification is one of the tools available to improve the properties of oils and fats and our recent studies have demonstrated that the lipase could specifically act on buriti oil to produce structured lipids rich in oleic acid, while preserving most of the minor compounds present in this oil. Still looking for ways to expand the applicability of this raw oil, in this work, we are interested in studying the behaviour of this structured oil in nanostructured lipid carriers (NLCs). EXPERIMENTAL APPROACH: The NLCs were produced with interesterified buriti oil and the stability, droplet size, electrical charge, microstructure, polymorphism and antioxidant activity of the samples were evaluated by ORAC and FRAP methods. RESULTS AND CONCLUSIONS: The results showed that the interesterification formed more unsaturated triacylglycerols (TAGs), and NLCs prepared with interesterified buriti oil had smaller droplets than NLCs with crude buriti oil. Particles remained stable throughout the storage period and NLCs exhibited complex polymorphism with the presence of three crystalline forms. The oxygen radical absorbance capacity (ORAC) value was approx. 23% higher in nanolipid carries with structured lipids than in the nanolipid carriers with crude buriti oil, and the ferric reducing antioxidant power (FRAP) value 16% higher, demonstrating the influence of interesterification on the antioxidant activity of nanocarriers. Thus, NLCs prepared with interesterified buriti oil had small droplets, high stability and antioxidant capacity, and have a potential for nutritional and biological applications. NOVELTY AND SCIENTIFIC CONTRIBUTION: This research showed that interesterification positively influenced the physicochemical properties of NLCs, producing the oil rich in oleic acid, high stability and antioxidant capacity. Therefore, it may be interesting to use these nanocarriers to obtain efficient carrier systems for future applications.

Interesterified palm oil impairs glucose homeostasis and induces deleterious effects in liver of Swiss mice.

BACKGROUND: Interesterified fats have largely replaced the partially hydrogenated oils which are the main dietary source of trans fat in industrialized food. This process promotes a random rearrangement of the native fatty acids and the results are different triacylglycerol (TAG) molecules without generating trans isomers. The role of interesterified fats in metabolism remains unclear. We evaluated metabolic parameters, glucose homeostasis and inflammatory markers in mice fed with normocaloric and normolipidic diets or hypercaloric and high-fat diet enriched with interesterified palm oil. METHODS: Male Swiss mice were randomly divided into four experimental groups and submitted to either normolipidic palm oil diet (PO), normolipidic interesterified palm oil diet (IPO), palm oil high-fat diet (POHF) or interesterified palm oil high-fat diet (IPOHF) during an 8 weeks period. RESULTS: When compared to the PO group, IPO group presented higher body mass, hyperglycemia, impaired glucose tolerance, evidence of insulin resistance and greater production of glucose in basal state during pyruvate in situ assay. We also observed higher protein content of hepatic PEPCK and increased cytokine mRNA expression in the IPO group when compared to PO. Interestingly, IPO group showed similar parameters to POHF and IPOHF groups. CONCLUSION: The results indicate that substitution of palm oil for interesterified palm oil even on normocaloric and normolipidic diet could negatively modulate metabolic parameters and glucose homeostasis as well as cytokine gene expression in the liver and white adipose tissue. This data support concerns about the effects of interesterified fats on health and could promote further discussions about the safety of the utilization of this unnatural fat by food industry.

Evaluation of cytotoxicity of nanolipid carriers with structured Buriti oil in the Caco-2 and HepG2 cell lines.

Buriti oil is rich in monounsaturated fatty acids, carotenoids and tocopherols and it is used for the treatment of various diseases. One strategy to restructure the triglycerides is enzymatic interesterification and nanocarriers have been employed to improve the solubility, bioavailability and stability of active compounds. This work aims to investigate the in vitro cytotoxicity of this structured oil in nanoemulsions and nanostructured lipid carriers to expand the applicability of the crude oil. None of the samples had a cytotoxic effect on Caco-2 and HepG2 cell lines at the concentrations tested. Structured lipids acted protecting against oxidative stress and lipid peroxidation. Additionally, no consumption of glutathione has been observed in both cells, and the compounds present in buriti oil are possibly acting as antioxidants. Thus, nanoparticles prepared with interesterified buriti oil had low cytotoxicity and high oxidative stability, with great potential for future applications.

Incorporation of Caprylic Acid into a Single Cell Oil Rich in Docosahexaenoic Acid for the Production of Specialty Lipids.

RESEARCH BACKGROUND: New sources of docosahexaenoic acid have recently been investigated aiming at infant formula fortification and dietary supplementation, among which the single cell oil with 40-50% of this acid. EXPERIMENTAL APPROACH: For this purpose, such an oil was blended with caprylic acid in amount substance ratio ranging from 1:1 to 5:1 and the blends were interesterified using either Novozym 435 or Lipozyme TL IM as the catalyst. The influence of the amount of excess free caprylic acid in the substrate, as well as the type of enzyme on the triacylglycerol rearrangement resulting from the synthesis of the structured lipids were evaluated. RESULTS AND CONCLUSIONS: The regiospecific lipase Lipozyme TL IM seemed to induce transesterification among single cell oil triacylglycerols preferably by acidolysis with caprylic acid, which was directly proportional to the ratio of this acid in the substrate. In reactions catalyzed by the non-regiospecific lipase Novozym 435, a higher incorporation of caprylic acid into single cell oil triacylglycerols was observed than when using Lipozyme TL IM, independently of the oil/caprylic acid molar ratio. NOVELTY AND SCIENTIFIC CONTRIBUTION: These results revealed the importance of combining the choice of the type of lipase, either regiospecific or not, with the amount ratios of free fatty acids and the substrate in acidolysis when aiming to produce structured lipids as a source of docosahexaenoic acid.

Physicochemical characterization and antimicrobial activity in novel systems containing buriti oil and structured lipids nanoemulsions.

Buriti oil nanoemulsions were prepared using non-interesterified buriti oil or buriti oil interesterified for 6 or 24 h (NBO, NBO6h, and NBO24 h), respectively. The aim was to investigate the effects of interesterified oils on the physicochemical and biological properties of nanoemulsions. Samples were stored at 4 and 25 °C for 30 days, and their physicochemical properties and biological activities were evaluated. The mean droplet diameter of nanoemulsions ranged from 196 to 270 nm. NBO24 h had the smallest droplet size and was the most stable during the storage period. Furthermore, NBO24 h demonstrating the good oxidative stability, had a high antioxidant capacity, and was less susceptible to droplet aggregation. NBO and NBO24 h had similar biological activity against Gram-negative bacteria (Escherichia coli O157: H7); bacterial growth was inhibited by at least 60% at 3.12 mg mL-1. The nanoemulsions have interesting properties for the production of pharmaceutical, cosmetic, and food formulations with antimicrobial activity.

Patent Landscape on Structured Lipids Produced by Enzyme Technology.

BACKGROUND: Lipid modification results in several benefits for the food industry, biotechnology advances and human health. Customizing bioactive lipids is very appealing because it improves the product's nutritional quality. Lipases are sustainable biocatalysts that can be reused, show selectivity towards substrates and reactions occur in mild conditions. OBJECTIVES: We aimed at systematically searching for patents deposited worldwide, that approached the production of structured lipids by using lipases as biocatalysts. METHOD: A patent-search strategy was set up in Questel-Orbit and the search strategy adopted was based on the combination of specific keywords in the title/abstract of the documents, encompassing thoroughly the search scope. We revised all patents relating structured lipids produced by enzyme reactions and provided an overview of the main objectives of the patents describing it, as well as a view of the principal depositors, years of publication and principal countries of deposit, as a mean to access the technological landscape on the subject. RESULTS: Forty-four documents, published over the last 34 years, were retrieved. Nine main patents' objectives were found, and the two major groups are: SL with bioactive properties and/or with fatty acids (FA) esterified at specific triacylglycerol positions and SL analogous of natural lipids. China, Japan and USA were the three main patent depositors. CONCLUSION: Although the number of patents retrieved was relatively low, this review indicates that SL production aiming at improvements in nutritional/health and/or physical attributes for food enhancement is a new field, and technological interest and innovation have been increasing over the last ten years.

The chemopreventive activity of butyrate-containing structured lipids in experimental rat hepatocarcinogenesis.

SCOPE: Emerging evidence indicates that the use of bioactive food components is a promising strategy to prevent the development of liver cancer. The goal of this study was to examine the chemopreventive effect of butyrate-containing structured lipids (STLs) produced by an enzymatic interesterification of tributyrin and flaxseed oil on rat hepatocarcinogenesis. METHODS AND RESULTS: Male Wistar rats were subjected to a classic "resistant hepatocyte" model of liver carcinogenesis and treated with STLs, tributyrin or flaxseed oil during the initial phases of hepatocarcinogenesis. Treatment with STLs and tributyrin strongly inhibited the development of preneoplastic liver lesions. The chemopreventive activity of tributyrin was associated with the induction of apoptosis and reduction of the expression of major activated hepatocarcinogenesis-related oncogenes. Treatment with STLs caused substantially greater inhibitory effects than tributyrin on oncogene expression. CONCLUSION: These results demonstrate that the tumor-suppressing activity of butyrate-containing STLs is associated with its ability to prevent and inhibit activation of major hepatocarcinogenesis-related oncogenes. Enrichment of histone H3K9me3 and H3K27me3 at the promoter of Myc and Ccnd1 genes may be related to the inhibitory effect on oncogene expression in the livers of STL-treated rats.

Potencial quimiopreventivo de lipídios estruturados obtidos por interesterificação da tributirina com o óleo de linhaça na hepatocarcinogênese / Chemopreventive potential of structured lipids obtained by interesterification of tributyrin with flaxseed oil in hepatocarcinogenesis

O carcinoma hepatocelular (HCC) apresenta mau prognóstico o que torna importante sua quimioprevenção. Nesse sentido, a tributirina (TB), um inibidor de desacetilases de histonas (HDACi), mostrou-se um quimiopreventivo promissor da hepatocarcinogênese. Avaliaram-se aqui efeitos quimiopreventivos de lipídios estruturados (EST) obtidos por interesterificação enzimática a partir da TB com o óleo de linhaça (LIN). Ratos foram tratados com EST (grupo EST; 165 mg/100g peso corpóreo [p.c]), TB (grupo TB; 200 mg/100g p.c), LIN (grupo LIN; 133 mg/100g p.c), mistura de TB com LIN (grupo LIN; 165 mg/100g p.c) ou maltodextrina (MD) (grupo MD; controle isocalórico; 300 mg/100g p.c) diariamente durante 8 semanas consecutivas por gavagem. Duas semanas após início dos tratamentos, os animais foram submetidos ao modelo de hepatocarcinogênese do "hepatócito resistente" (RH). Os grupos EST e TB apresentaram atividade quimiopreventiva bloqueadora e supressora, respectivamente, da hepatocarcinogênese. TB induziu a apoptose, ao contrário dos EST. O tratamento com TB resultou na acetilação e trimetilação da H3K9 e H3K27, enquanto EST atuaram somente na trimetilação das mesmas. Quando analisada a expressão de genes envolvidos com modificações em histonas, EST e TB reduziram a expressão de Ezh2 e de Hdac4. Por outro lado, somente os EST aumentaram a expressão de Hdac6. Tal efeito por parte dos EST merece ser mais investigado, uma vez que esta desacetilase vem sendo sugerida como alvo potencial para o desenvolvimento de fármacos. Em conclusão, a atividade quimiopreventiva de EST e da TB envolve na hepatocarcinogênese experimental mecanismos epigenéticos que podem ou não ser distintos

Hepatocellular carcinoma (HCC) has a poor prognosis, which makes its chemoprevention important. Tributyrin (TB), which is a histone deacetylase inhibitor (HDACi), is a promising chemopreventive agent of hepatocarcinogenesis. The chemopreventive effects of structured lipids (STLs) that were obtained by the enzymatic interesterification of TB with flaxseed oil (FSO) were evaluated in the present study. Rats were treated with STLs (STL group, 165 mg/100 g body weight (bw)), TB (TB group, 200 mg/100 g bw), FSO (FSO group, 133 mg/100 g bw), TB mixed with FSO (BLD group, 165 mg/100g bw) or maltodextrin (MD) (MD group; isocaloric control; 300 mg/100 g bw) daily for eight consecutive weeks by gavage. Two weeks after the initiation of treatment, the animals were subjected to the resistant hepatocyte hepatocarcinogenesis model (RH). The STL and TB groups developed blocker and suppressive chemopreventive activity against hepatocarcinogenesis, respectively. TB treatment induced apoptosis, unlike the STL treatment. Additionally, TB treatment resulted in the acetylation and trimethylation of H3K9 and H3K27, whereas the STLs acted only in the trimethylation of these histones. When analyzing the expression of genes involved in histone modifications, the STLs and TB reduced enhancer of zeste homolog 2 (Ezh2) and histone deacetylase 4 (Hdac4) gene expression. Conversely, only the STLs increased Hdac6 gene expression. This effect of the STLs warrants further investigation because this deacetylase has been suggested as a potential drug development target. In conclusion, the chemopreventive activities of the STLs and TB in experimental hepatocarcinogenesis involve epigenetic mechanisms that may be distinct

Lipídios estruturados obtidos por interesterificação da tributirina com óleo de linhaça e seu potencial quimiopreventivo durante a fase de promoção inicial da hepatocarcinogênese experimental em ratos / Structured lipids obtained from intersterification of tributyrin and flax seed oil and their chemopreventive potential during early promotion phase of experimental hepatocarcinogenesis in rats

A combinação de agentes quimiopreventivos com diferentes mecanismos de ação tem sido considerada uma estratégia promissora para a prevenção do câncer. Dentre os diversos compostos bioativos em alimentos, destacam-se a tributirina, um pró-fármaco do ácido butírico presente em laticínios e produzido pela fermentação de fibras dietéticas, e o óleo de linhaça, fonte de ácido alfa linolênico. Nesse contexto, foi avaliada a atividade quimiopreventiva de lipídios estruturados obtidos a partir da interesterificação enzimática de tributirina e óleo de linhaça durante a fase de promoção inicial da hepatocarcinogênese experimental. Ratos Wistar machos submetidos ao modelo do hepatócito resistente receberam diariamente, por via intragástrica (i.g), maltodextrina, óleo de linhaça, tributirina, a mistura não esterificada ou lipídios estruturados durante a fase de promoção inicial. O tratamento com lipídios estruturados demonstrou atividade quimiopreventiva comparável à da tributirina, mesmo resultando em menor concentração hepática de ácido butírico. Tanto a tributirina quanto os lipídios estruturados não inibiram a proliferação celular em lesões preneoplásicas, mas induziram a apoptose naquelas em remodelação. Os efeitos inibitórios da tributirina em fases iniciais da hepatocarcinogênese experimental estão relacionados ao aumento da acetilação de histonas e à modulação de processos de translocação nuclear da p53. No presente estudo, foi observado aumento substancial da razão nuclear/citoplasmática de p53 e importina-alfa em fígados de animais submetidos ao modelo e tratados com tributirina, mas não nos tratados com lipídios estruturados. Por outro lado, o tratamento com lipídios estruturados reduziu a expressão dos oncogenes Bcl2, Ccnd2, Pdgfa, Vegfa e aumentou a expressão dos genes supressores de tumor Cdh13, Fhit e Socs3. Assim, embora o potencial quimiopreventivo dos lipídios estruturados seja comparável ao da tributirina, os resultados sugerem que o novo composto não exibe atividade de HDACi, e que seus efeitos inibitórios na hepatocarcinogênese possam ser atribuídos à modulação da expressão de oncogenes e genes supressores de tumor

Combination of chemopreventive agents with different mechanisms of action has been considered a promising strategy to cancer prevention. Among several bioactive food compounds, tributyrin, a butyric acid prodrug obtained from dairy products and dietetic fiber fermentation, and flax seed oil, a rich source of alpha linolenic acid have shown chemopreventive potential. Here, we evaluated the chemopreventive activity of structured lipids obtained by enzymatic interesterification of tributyrin and flax seed oil during the early promotion phase of experimental hepatocarcinogenesis. Male Wistar rats subjected to the resistant hepatocyte model were treated daily, i.g, with maltodextrin, flax seed oil, tributyrin, non-sterified blend, or structured lipids. Treatment structured lipids showed similar chemopreventive activity compared to tributyrin, even when structured lipids yielded lower concentrations of butyric in the liver. Tributyrin and structured lipids did not inhibit cell proliferation in preneoplastic lesions, but both of them induced apoptosis in remodeling preneoplastic lesions. In addition, histone acetylation and p21 restored expression tributyrin molecular mechanisms were related to modulation of p53 nuclear shuttling mechanisms. In the present study, it was observed a substantial increase in p53 nuclear/cytoplasmic ratio and importin-alpha in preneoplastic livers of tributyrin treated rats, but not in those treated with structured lipids. In contrast, treatment structured lipids downregulated expression of major oncogenes Bcl2, Ccnd2, Pdgfa, and Vegfa; and upregulated expression of critical tumor suppressor genes, Cdh13, Socs3 and Fhit. Hence, although structured lipids and tributyrin show similar chemopreventive potential, the results suggest that the new compound does not exhibit HDACi activity, and that its inhibitory effects may be attributed to the modulation of oncogenes and tumor suppressor genes expression

Síntese de lipídios estruturados por interesterificação de banha e óleo de soja para obtenção de sucedâneo da gordura do leite humano / Synthesis of structure lipids by interesterification of lard and soybean oil for obtain human milk fat substitute

O leite humano é um alimento completo, possui todos os nutrientes em quantidade e qualidade necessárias, proporciona proteção contra infecções e alergias e estimula o sistema imunológico. Os lipídios do leite humano são fonte energética; veículos para as vitaminas lipossolúveis; contêm ácidos graxos poliinsaturados necessários para o desenvolvimento cerebral; contêm precursores de prostaglandinas e hormônios; e são constituintes essenciais para as membranas celulares. Muitas mães, por razões médicas, metabólicas ou econômicas, dependem de fórmulas artificiais para alimentar seus filhos. Portanto, a composição dos ácidos graxos e a sua distribuição nas cadeias dos triacilgliceróis devem ser alvos de estudos em fórmulas infantis, sendo que os triacilgliceróis do leite humano devem servir de modelo para os componentes lipídicos. Recentemente, diversos estudos apontam a interesterificação como alternativa para a produção de sucedâneos da gordura do leite humano. Assim, o objetivo deste trabalho foi explorar diversas possibilidades da modificação lipídica para a obtenção deste sucedâneo. As matérias-primas utilizadas foram banha e óleo de soja, gorduras facilmente obtidas e de baixo custo no Brasil. Neste trabalho, foram produzidos lipídios estruturados por interesterificação química e enzimática, sendo que na interesterificação enzimática foram utilizadas duas lipases puras, a AY30TM (Candida cylindracea) e a M10TM (Mucor circinelloides), e a lipase imobilizada Lipozyme TL IM (Thermomices lanuginosa). Os lipídios estruturados foram submetidos a análises de suas propriedades químicas e físicas, que foram comparadas às propriedades da gordura do leite humano e do lipídio estruturado comercial BetapolTM. Os resultados apresentados demonstraram a viabilidade da interesterificação como método de modificação para obtenção de lipídios estruturados sucedâneos da gordura do leite humano. Tendo em vista a possibilidade de maior controle reacional devido à especificidade das lipases e a busca por processos ambientalmente corretos, a interesterificação enzimática mostra-se alternativa mais interessante para esta modificação lipídica. A mistura de banha e óleo de soja demonstrou ser opção viável para a produção de sucedâneos da gordura do leite humano

Human milk is a complete food with all the nutrients in quantity and quality provides protection against infections and allergies and stimulates the immune system. The lipids of human milk are source of energy; vehicles for liposoluble vitamins; contain polyunsaturated fatty acids for brain development; contain precursors of prostaglandins, hormones; and are essential constituents to the cell membranes. Many mothers, for medical, metabolic or economic reasons, depend on artificial formulas to feed their children. Therefore, the composition of fatty acids and their distribution chains in the triacylglycerols must be targets of studies on infant formula, and the human milk triacylglycerols should be a model for the lipid components. Recently, several studies indicate the interesterification like an alternative for the production of substitutes of human milk fat. The objective of this study was to explore various possibilities of lipid modification to achieve this substitute. The raw materials used were lard and soybean oil, fats easily obtained and cheap in Brazil. In this work, were produced structured lipids by chemical and enzymatic interesterification. For enzymatic interesterification were used two pure lipases, AY30 TM (Candida cylindracea) and M10 (M (Mucor circinelloides) and one immobilized lipase, Lipozyme TL IM (Thermomices lanuginosa). The structured lipids were submitted to analysis of their chemical and physical properties, which were compared with the human milk fat and the structured commercial lipid Betapol TM. The results demonstrated the feasibility of interesterification as a method of modification to obtain structured lipids substitutes of human milk fat. The possibility of greater control reaction because the specificity of lipases and the search for environmentally correct procedures makes enzymatic interesterification the most attractive alternative for modifying lipids. The mixture of soybean oil and lard is a viable alternative for the production of human milk fat substitutes