Exploring the use of hydroxytyrosol and some of its esters in food-grade nanoemulsions: establishing connection between structure and efficiency

The efficiency of HT and that of some of its hydrophobic derivatives and their distribution and effective concentrations were investigated in fish oil-in-water nanoemulsions. For this purpose, we carried out two sets of independent, but complementary, kinetic experiments in the same intact fish nanoemulsions. In one of them, we monitored the progress of lipid oxidation in intact nanoemulsions by monitoring the formation of conjugated dienes with time. In the second set of experiments, we determined the distributions and effective concentrations of HT and its derivatives in the same intact nanoemulsions as those employed in the oxidation experiments. Results show that the antioxidant efficiency is consistent with the “cut-off” effect—the efficiency of HT derivatives increases upon increasing their hydrophobicity up to the octyl derivative after which a further increase in the hydrophobicity decreases their efficiency. Results indicate that the effective interfacial concentration is the main factor controlling the efficiency of the antioxidants and that such efficiency strongly depends on the surfactant concentration and on the oil-to-water (o/w) ratio employed to prepare the nanoemulsions.Agencia Estatal de Investigación | Ref. PID2022-136443OB-I0

Efficiency of δ-Tocopherol in Inhibiting Lipid Oxidation in Emulsions: Effects of Surfactant Charge and of Surfactant Concentration

Charged interfaces may play an important role in the fate of chemical reactions. Alterations in, for instance, the interfacial acidity of emulsions induced by the charge of the surfactant head group and associated counterions may change the ionization status of antioxidants, modifying their effective concentrations. The chemical reactivity between interfacial reactants and charged species of opposite charge (protons, metallic ions, etc.) is usually interpreted in terms of pseudophase ion-exchange models, treating the distribution of charged species in terms of partitioning and ion exchange. Here, we focus on analyzing the effects of charged interfaces on the oxidative stability of soybean oil-in-water (o/w) emulsions prepared with anionic (sodium dodecyl sulfate, SDS), cationic (cetyltrimethylammonium bromide, CTAB) and neutral (Tween 20) surfactants, and some of their mixtures, in the presence and absence of δ-tocopherol (δ-TOC). We have also determined the effective concentrations of δ-TOC in the oil, interfacial and aqueous regions of the intact emulsions. In the absence of δ-TOC, the relative oxidative stability order was CTAB < TW20 ~ TW20/CTAB < SDS. Surprisingly, upon the addition of δ-TOC, the relative order was SDS ≈ TW20 << TW20/CTAB < CTAB. These apparently surprising results can be rationalized in terms of the nice correlation that exists between the relative oxidative stability and the effective interfacial concentrations of δ-TOC in the various emulsions. The results emphasize the importance of considering the effective interfacial concentrations of antioxidants in interpreting their relative efficiency in emulsions

Molecular Design of Interfaces of Model Food Nanoemulsions: A Combined Experimental and Theoretical Approach

The composition and structure of the interfacial region of emulsions frequently determine its functionality and practical applications. In this work, we have integrated theory and experiments to enable a detailed description of the location and orientation of antioxidants in the interfacial region of olive-oil-in-water nanoemulsions (O/W) loaded with the model gallic acid (GA) antioxidant. For the purpose, we determined the distribution of GA in the intact emulsions by employing the well-developed pseudophase kinetic model, as well as their oxidative stability. We also determined, by employing an in silico design, the radial distribution functions of GA to gain insights on its insertion depth and on its orientation in the interfacial region. Both theoretical and experimental methods provide comparable and complementary results, indicating that most GA is located in the interfacial region (~81.2%) with a small fraction in the aqueous (~18.82%). Thus, GA is an effective antioxidant to inhibit lipid oxidation in emulsions not only because of the energy required for its reaction with peroxyl radical is much lower than that between the peroxyl radical and the unsaturated lipid but also because its effective concentration in the interfacial region is much higher than the stoichiometric concentration. The results demonstrate that the hybrid approach of experiments and simulations constitutes a complementary and useful pathway to design new, tailored, functionalized emulsions to minimize lipid oxidation

Inhibition of carnitine palmitoyl-transferase 1A in hepatic stellate cells protects against fibrosis

Background & Aims The pathogenesis of liver fibrosis requires activation of hepatic stellate cells (HSCs); once activated, HSCs lose intracellular fatty acids but the role of fatty acid oxidation and carnitine palmitoyltransferase 1A (CPT1A) in this process remains largely unexplored. Methods CPT1A was found in HSCs of patients with fibrosis. Pharmacological and genetic manipulation of CPT1A were done in HSCs human cell lines and primary HCSs. Finally, we induced fibrosis in mice lacking CPT1A specifically in HSCs. Results Here we show that CPT1A expression is elevated in HSCs of patients with NASH, showing a positive correlation with the fibrosis score. This was corroborated in rodents with fibrosis, as well as in primary human HSCs and LX-2 cells activated by transforming growth factor β1 (TGFβ1) and fetal bovine serum (FBS). Furthermore, both pharmacological and genetic silencing of CPT1A prevent TGFβ1- and FBS-induced HSC activation by reducing mitochondrial activity. The overexpression of CPT1A, induced by saturated fatty acids and reactive oxygen species, triggers mitochondrial function and the expression of fibrogenic markers. Finally, mice lacking CPT1A specifically in HSCs are protected against fibrosis, induced by a choline-deficient high fat diet, a methionine- and choline-deficient diet, or treatment with carbon tetrachloride. Conclusions These results indicate that CPT1A plays a critical role in activation of HSCs and is implicated in the development of liver fibrosis, making it a potentially actionable target for fibrosis treatment. Lay summary We show that CPT1A located in HSCs is elevated in patients and mice models with fibrosis, and that CPT1A induces the activation of these cells. Inhibition of CPT1A ameliorates fibrosis by preventing the activation of HSCs

Inhibition of carnitine palmitoyltransferase 1A in hepatic stellate cells protects against fibrosis

One of the most common types of fibrotic liver occurs in patients with non-alcoholic fatty liver disease (NAFLD), which may develop into non-alcoholic steatohepatitis (NASH). Hepatic stellate cells (HSCs) are the primary fibrogenic cell type activated following liver injury, moving from a quiescent phenotype rich in vitamin A into activated myofibroblast-like cells with proliferative and migratory properties.This work has been supported by grants from FEDER/Ministerio de Ciencia, Innovación y Universidades-Agencia Estatal de Investigación (DS and LH: SAF2017-83813-C3-1-R; MLMC: RTC2019-007125-1; CD: BFU2017-87721; ML: RTI2018–101840-B-I00; RN: RTI2018-099413-B-I00 and RED2018-102379-T; MLMC: SAF2017-87301-R; TCD: RTI2018-096759-A-100), Xunta de Galicia (ML: 2016-PG068; RN: 2015-CP080 and 2016-PG057), Fundación BBVA (RN and MLM), Proyectos Investigación en Salud (MLMC: DTS20/00138), Sistema Universitario Vasco (PA: IT971-16); Fundacion Araucaria (ML and RN), Gilead Sciences International Research Scholars Program in Liver Disease (MVR), Marató TV3 Foundation (DS: 201627), Government of Catalonia (DS: 2017SGR278) and European Foundation for the Study of Diabetes (RN). This research also received funding from the European Community’s H2020 Framework Programme (ERC Synergy Grant-2019-WATCH- 810331, to RN, VP and MS). Centro de Investigación Biomédica en Red (CIBER) de Fisiopatología de la Obesidad y Nutrición (CIBERobn), Centro de Investigación Biomédica en Red (CIBER) de Enfermedades Hepáticas y Digestivas (CIBERehd). CIBERobn and CIBERehd are initiatives of the Instituto de Salud Carlos III (ISCIII) of Spain which is supported by FEDER funds. We thank MINECO for the Severo Ochoa Excellence Accreditation to CIC bioGUNE (SEV-2016-0644)S