RESUMEN
BACKGROUND & AIMS: Medium-chain triglycerides (TG) (MCT) and fish oil (FO) TG are incorporated as the core TG component into intravenous (IV) lipid emulsions for infusion in parenteral nutrition. Bolus injections of IV emulsions, on the other hand, have emerged as a novel therapeutic approach to treat various acute disorders. However, intravascular metabolism and organ delivery of acute IV injection of emulsions containing both MCT and FO are not fully defined, nor have they been characterized across common experimental animal models. We characterized and compared blood clearance kinetics and organ distribution of bolus injections of MCT/FO emulsions among different animal species. We also examined whether sex differences or feeding status can affect catabolic properties of MCT/FO lipid emulsions. DESIGN: Blood clearance rates of lipid emulsions with specific TG composition were compared in rats IV injected with [3H]cholesteryl hexadecyl ether labeled pure n-6 long-chain (LCT) and n-3 FO TG lipid emulsions, or emulsions containing MCT and FO at different ratios (wt/wt), which include 8:2 (80% MCT: 20% FO), 5:4:1 (50% MCT: 40% LCT: 10% FO) and SMOF (30% LCT: 30% MCT: 25% olive oil: 10% FO). Dose-response effects (0.016 mg-1.6 mg TG/g body weight) of the MCT/FO 8:2 emulsions on blood clearance properties and organ delivery were determined in both mice and rats. Blood clearance kinetics and organ uptake of MCT/FO 8:2 emulsions were compared between male and female rats and between fed and fasted rats. Changes in plasma lipid profiles after acute injections of MCT/FO 8:2 lipid emulsion at different doses (0.043, 0.133, and 0.4 mg TG/g body weight) were characterized in non-human primates (Cynomolgus monkeys). RESULTS: MCT/FO 8:2 emulsion was cleared faster in rats when compared with other emulsions with different TG contents. Mice had faster blood clearance and higher fractional catabolic rates (FCR) when compared with the rats injected with MCT/FO 8:2 emulsions regardless of the injected doses. Mice and rats had similar plasma TG and free fatty acid (FFA) levels after low- or high-dose injections of the MCT/FO emulsion. Tissue distribution of the MCT/FO 8:2 lipid emulsion are comparable between mice and rats, where liver had the highest uptake per recovered dose among all organs (>60%). Feeding status and sex differences did not alter the blood clearance rate of the MCT/FO 8:2 emulsion in rats. In a nonhuman primate model, dose-response increases in plasma TG and FFA were observed after IV injection of MCT/FO 8:2 emulsions within the 1st 10 min. CONCLUSION: A lipid emulsion containing both MCT and FO TG is cleared rapidly in blood and readily available for organ uptake in rodent and primate animal models. Characterization of the blood clearance properties of the MCT/FO 8:2 emulsion administered in various animal models may provide further insight into the safety and efficacy profiles for future therapeutic use of bolus injections of MCT/FO emulsions in humans.
Asunto(s)
Emulsiones Grasas Intravenosas/farmacocinética , Aceites de Pescado/farmacocinética , Lípidos/sangre , Triglicéridos/farmacocinética , Animales , Disponibilidad Biológica , Femenino , Cinética , Hígado/metabolismo , Macaca fascicularis , Masculino , Tasa de Depuración Metabólica , Ratones , Modelos Animales , Aceite de Oliva/farmacocinética , Nutrición Parenteral , Ratas , Triglicéridos/químicaRESUMEN
It is currently unclear how the process of fat digestion occurs in the mouth of humans. This pilot study therefore aimed to quantify the levels of lipolytic activity at different sites of the mouth and in whole saliva. Samples of whole saliva and from 4 discrete sites in the oral cavity were collected from 42 healthy adult participants. All samples were analyzed for lipolytic activity using two different substrates (olive oil and the synthetic 1,2-o-dilauryl-rac-glycero-3-glutaric acid-(6'-methylresorufin) ester (DGGR)). Blandâ»Altman analyses suggested that the two assays gave divergent results, with 91% and 23% of site-specific and 40% and 26% of whole-saliva samples testing positive for lipolytic activity, respectively. Non-parametric multiple comparisons tests highlighted that median (IQR) of lipolytic activity (tested using the olive oil assay) of the samples from the parotid 20.7 (11.7â»31.0) and sublingual 18.4 (10.6â»47.2) sites were significantly higher than that of whole saliva 0.0 (0.0â»35.7). In conclusion, lipolysis appears to occur in the oral cavity of a proportion of individuals. These findings give a preliminary indication that lipolytic agent activity in the oral cavity may be substrate-specific but do not discount that the enzyme is from sources other than oral secretions (e.g., microbes, gastric reflux).
Asunto(s)
Grasas de la Dieta/farmacocinética , Glutaratos/farmacocinética , Lipasa/metabolismo , Lipólisis , Boca/metabolismo , Aceite de Oliva/farmacocinética , Oxazinas/farmacocinética , Saliva/enzimología , Adulto , Bioensayo , Grasas de la Dieta/metabolismo , Femenino , Glutaratos/metabolismo , Humanos , Masculino , Aceite de Oliva/metabolismo , Oxazinas/metabolismo , Glándula Parótida , Glándula Sublingual , Lengua , Adulto JovenRESUMEN
SCOPE: Phenolic compounds are minor components of extra virgin olive oil (EVOO). Secoiridoids are the major components contributing to the phenolic content of EVOO. Information is lacking regarding their potential as biomarkers for EVOO intake. METHODS AND RESULTS: Healthy volunteers (n = 9) ingested 50 mL of EVOO in a single dose containing 322 mg kg-1 total phenolic content (caffeic acid equivalents) and 6 mg 20 g-1 hydroxytyrosol and its derivatives. Plasma is collected before (0 h) and at 0.5, 1, 2, 4, and 6 h after ingestion. Urine samples are collected prior to ingestion (0 h) and at 0-4, 4-8, 8-15, and 15-24 h. Samples are analyzed by UPLC coupled with an Exactive Orbitrap MS. Partial least squares discriminant analysis with orthogonal signal correction is applied to screen for metabolites that allow sample discrimination. Plasma biomarkers and urine biomarkers are selected although individual variability is observed among volunteers. Results are in accordance with in vitro experiments performed (in vitro digestion and hepatic microsomal activity assays). CONCLUSIONS: Plasma (elenolic acid + H2 ; p-HPEA-EA + H2 + glucuronide) and urinary (3,4-DHPEA-EA, 3,4-DHPEA-EA + H2 +glucuronide, methyl 3,4-DHPEA-EA + H2 +glucuronide) secoiridoid compounds are selected as biomarkers to monitor EVOO intake showing good predictive ability according to multivariate analysis.