Inhibition of GPR120 signaling in intestine ameliorates insulin resistance and fatty liver under high-fat diet feeding.

G protein-coupled receptor (GPR) 120 is expressed in enteroendocrine cells secreting glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide/gastric inhibitory polypeptide (GIP), and cholecystokinin (CCK). Although GPR120 signaling in adipose tissue and macrophages has been reported to ameliorate obesity and insulin resistance in a high long-chain triglyceride (LCT) diet, intestine-specific roles of GPR120 are unclear. To clarify the metabolic effect of GPR120 in the intestine, we generated intestine-specific GPR120-knockout (GPR120int-/-) mice. In comparison with floxed GPR120 (WT) mice, GPR120int-/- mice exhibited reduced GIP secretion and CCK action without change of insulin, GLP-1, or peptide YY (PYY) secretion after a single administration of LCT. Under a high-LCT diet, GPR120int-/- mice showed a mild reduction of body weight and substantial amelioration of insulin resistance and fatty liver. Moreover, liver and white adipose tissue (WAT) of GPR120int-/-mice exhibited increased Akt phosphorylation and reduced gene expression of suppressor of cytokine signaling (SOCS) 3, which inhibits insulin signaling. In addition, gene expression of inflammatory cytokines in WAT and lipogenic molecules in liver were reduced in GPR120int-/- mice. These findings suggest that inhibition of GPR120 signaling in intestine ameliorates insulin resistance and fatty liver under high-LCT diet feeding.NEW & NOTEWORTHY We generated novel intestine-specific GPR120-knockout (GPR120int-/-) mice and investigated the metabolic effect of GPR120 in the intestine. GPR120int-/- mice exhibited a reduction of GIP secretion and CCK action after a single administration of LCT. Under a high-LCT diet, GPR120int-/- mice showed mild improvement in obesity and marked amelioration of insulin resistance and hepatic steatosis. Our results indicate an important role of intestinal GPR120 on insulin resistance and hepatic steatosis.

Early-life stress and dietary fatty acids impact the brain lipid/oxylipin profile into adulthood, basally and in response to LPS.

Brain lipid dysregulation is a hallmark of depression and Alzheimer's disease, also marked by chronic inflammation. Early-life stress (ELS) and dietary intake of polyunsaturated fatty acids (PUFAs) are risk factors for these pathologies and are known to impact inflammatory processes. However, if these early-life factors alter brain lipid homeostasis on the long-term and thereby contribute to this risk remains to be elucidated. We have recently shown that an early diet enriched in omega(ω)-3 PUFAs protected against the long-term negative effects of ELS on cognition and neuroinflammation. Here, we aim to understand if modulation of brain lipid and oxylipin profiles contributes to the detrimental effects of ELS and the protective ones of the diet. We therefore studied if and how ELS and early dietary PUFAs modulate the brain lipid and oxylipin profile, basally as well as in response to an inflammatory challenge, to unmask possible latent effects. Male mice were exposed to ELS via the limited bedding and nesting paradigm, received an early diet with high or low ω6/ω3 ratio (HRD and LRD) and were injected with saline or lipopolysaccharide (LPS) in adulthood. Twenty-four hours later plasma cytokines (Multiplex) and hypothalamic lipids and oxylipins (liquid chromatography tandem mass spectrometry) were measured. ELS exacerbated the LPS-induced increase in IL-6, CXCL1 and CCL2. Both ELS and diet affected the lipid/oxylipin profile long-term. For example, ELS increased diacylglycerol and LRD reduced triacylglycerol, free fatty acids and ceramides. Importantly, the ELS-induced alterations were strongly influenced by the early diet. For example, the ELS-induced decrease in eicosapentaenoic acid was reversed when fed LRD. Similarly, the majority of the LPS-induced alterations were distinct for control and ELS exposed mice and unique for mice fed with LRD or HRD. LPS decreased ceramides and lysophosphotidylcholine, increased hexosylceramides and prostaglandin E2, reduced triacylglycerol species and ω6-derived oxylipins only in mice fed LRD and ELS reduced the LPS-induced increase in phosphatidylcholine. These data give further insights into the alterations in brain lipids and oxylipins that might contribute to the detrimental effects of ELS, to the protective ones of LRD and the possible early-origin of brain lipid dyshomeostasis characterizing ELS-related psychopathologies.

Eficacia y seguridad de la fórmula nutricional con bajo contenido lipídico y alto en triglicéridos de cadena media en pacientes pediátricos con quilotorax / Efficacy and safety of nutritional formula with low lipid content and high medium chain triglycerides in pediatric patients with chylothorax

ANTECEDENTES: En el marco de la metodología ad hoc para evaluar solicitudes de tecnologías sanitarias, aprobada mediante Resolución de Instituto de Evaluación de Tecnologías en Salud e Investigación N° 111-IETSI-ESSALUD-2021, se ha elaborado el presente dictamen, el que expone la evaluación de la eficacia y seguridad de la fórmula nutricional con bajo contenido lipídico y alto en triglicéridos de cadena media (TCM) en pacientes pediátricos con quilotórax. Así, el médico Marco Morales Acosta, especialista en pediatría, del Servicio de Pediatría Clínica del Hospital Nacional Edgardo Rebagliati Martins, perteneciente a la Red Prestacional Rebagliati, siguiendo la Directiva N.° 003-IETSIESSALUD-2016, envió al Instituto de Evaluación de Tecnologías en Salud e Investigación - IETSI la solicitud de uso, por fuera del petitorio del producto: fórmula nutricional con bajo contenido lipídico y alto en TCM. ASPECTOS GENERALES: El quilotórax es la acumulación de líquido linfático en la cavidad pleural, que resulta de fugas provenientes de los vasos linfáticos (Tutor, 2014). El quilotórax se diagnostica tras la detección de concentración de triglicéridos en el líquido pleural mayor a 110 mg/dl (Rocha et al., 2006). En la población pediátrica, el quilotórax es causado, principalmente, por defectos congénitos o por daños al conducto torácico como resultado de complicaciones posquirúrgicas (Soto-Martinez & Massie, 2009). La incidencia aproximada del quilotórax congénito es de 1 por cada 10,000 nacidos vivos (Zheng et al., 2020); mientas que, la incidencia del quilotórax post-cirugía cardíaca en población pediátrica varía de 0.85 % a 9.2 % (Rocha et al., 2006). A pesar de no tener alta incidencia, los pacientes menores de 18 años con quilotórax tienen riesgo de mortalidad de hasta el 50 % cuando no reciben tratamiento, mayor morbilidad y tienen mayor tiempo de estancia hospitalaria (mediana = 38.8 días; rango intercuartil [R1Q) = 27.8 - 52.3, frente a mediana = 27.0 días, RIQ = 18.9 - 39.1 días; p < 0.001), comparado con los que no desarrollaron quilotórax luego de una cirugía cardiaca (Bai et al., 2021; Yeh et al., 2013). METODOLOGÍA: Se llevó a cabo una búsqueda bibliográfica exhaustiva con el objetivo de identificar la mejor evidencia disponible sobre la eficacia y seguridad de la fórmula con bajo contenido lipídico y alto contenido de TCM. La búsqueda bibliográfica se realizó en las bases de datos bibliográfica de PubMed, The Cochrane Library y LILACS. Asimismo, se realizó una búsqueda manual dentro de las páginas web pertenecientes a grupos que realizan evaluación de tecnologías sanitarias (ETS) y guías de práctica clínica (GPC) incluyendo la World Health Organization (WHO), la National Institute for Health and Care Excellence (NICE), la Agency for Healthcare Research and Quality's (AHRQ), la Scottish Intercollegiate Guidelines Network (SIGN), la New Zealand Guidelines Group (NZGG), la National Health and Medical Research Council (NHMRC), el Instituto de Evaluación de Tecnologías en Salud e Investigación (IETSI), el Centro Nacional de Excelencia Tecnológica en Salud (CENETEC), la Canadian Agency for Drugs and Technologies in Health (CADTH), el Institute for Quality and Efficiency in Health Care (IQWIG), el Scottish Medicines Consortium (SMC), la Comissáo Nacional de Incorporção de Tecnologias no Sistema Único de Saúde (CONITEC), el Instituto de Evaluación Tecnológica en Salud (IETS) y el Instituto de Efectividad Clínica y Sanitaria (IECS). Finalmente, se realizó una búsqueda adicional en la página web de registro de ensayos clínicos (EC) www.clinicaltrials.gov, para identificar EC en curso o que no hayan sido publicados aún. RESULTADOS: Luego de la búsqueda bibliográfica, no se encontró alguna GPC, ETS o ECA fase III que cumpla con los primeros criterios de inclusión. Tras la ampliación de los criterios de elegibilidad, se incluyeron tres estudios observacionales (Bellini et al., 2012; Cormack et al., 2004; Zheng et al., 2020). Dos de estos estudios (Cormack 2004 & Zheng 2020), usaron el diseño de cohortes de tipo retrospectivo, y compararon el tiempo hasta la resolución del quilotórax (solo en Zheng et al 2020), duración de drenaje pleural (solo en Cormack et al 2004), tiempo de hospitalización y mortalidad en los pacientes con quilotórax posquirúrgico que usaron la fórmula con bajo contenido lipídico alto en TCM versus los que usaron la NPT. El último estudio (Bellini et al 2012), se trata de una serie de casos de neonatos con quilotórax congénito, donde se reporta la experiencia de tratamiento de estos pacientes usando la fórmula nutricional con bajo contenido lipídico y alto en TCM con o sin la octreotida. Los desenlaces de interés evaluados fueron la resolución del quilotórax y la mortalidad. CONCLUSIÓN: Por lo expuesto, el Instituto de Evaluación de Tecnologías en Salud e Investigación aprueba el uso de la fórmula con bajo contenido lipídico y alto en TCM, con o sin octreotida, en pacientes menores de 18 años con diagnóstico de quilotórax debido a cualquier etiología (congénito o adquirido) que pueden recibir nutrición enteral, como producto farmacéutico no incluido en el Petitorio Farmacológico de EsSalud, según lo establecido en el Anexo N° 1. La vigencia del presente dictamen preliminar es de un año a partir de la fecha de publicación. Así, la continuación de dicha aprobación estará sujeta a la evaluación de los resultados obtenidos y de mayor evidencia que pueda surgir en el tiempo.

A Mixed-Lipid Emulsion Containing Fish Oil for the Parenteral Nutrition of Preterm Infants: No Impact on Visual Neuronal Conduction.

Fish oil is rich in omega-3 fatty acids and essential for neuronal myelination and maturation. The aim of this study was to investigate whether the use of a mixed-lipid emulsion composed of soybean oil, medium-chain triglycerides, olive oil, and fish oil (SMOF-LE) compared to a pure soybean oil-based lipid emulsion (S-LE) for parenteral nutrition had an impact on neuronal conduction in preterm infants. This study is a retrospective matched cohort study comparing preterm infants <1000 g who received SMOF-LE in comparison to S-LE for parenteral nutrition. Visual evoked potentials (VEPs) were assessed longitudinally from birth until discharge. The latencies of the evoked peaks N2 and P2 were analyzed. The analysis included 76 infants (SMOF-LE: n = 41 and S-LE: n = 35) with 344 VEP measurements (SMOF-LE: n= 191 and S-LE n = 153). Values of N2 and P2 were not significantly different between the SMOF-LE and S-LE groups. A possible better treatment effect in the SMOF-LE group was seen as a trend toward a shorter latency, indicating faster neural conduction at around term-equivalent age. Prospective trials and follow-up studies are necessary in order to evaluate the potential positive effect of SMOF-LE on neuronal conduction and visual pathway maturation.

Home parenteral nutrition patients on mixed oil lipid emulsion have a higher rate of hospitalizations compare to those on soybean oil- a prospective 2-year cohort study.

BACKGROUND & AIMS: Mixed oil intravenous lipid emulsion (MO ILE) that contains 30% soybean oil (SO), 30% medium chain triglycerides, 25% olive oil and 15% fish oil can benefit hospitalized patients receiving parenteral nutrition (PN) but there are very few studies on its long-term use. Our goal was to evaluate the clinical outcomes of adults receiving home PN (HPN) with MO versus those receiving SO ILE over a 2-year period. METHOD: This is a retrospective analysis of data collected prospectively from a cohort of patients recorded in the Canadian HPN Registry over a 2-year period. HPN patients from academic programs across Canada were entered in the Registry according to a validated protocol. For this study, demographic, nutritional, laboratory and clinical data were extracted from January 1st 2015, when MO lipid emulsion became available in Canada, to July 24th 2019. Clinical data for each patient included: number of hospitalizations, number of hospitalizations related to HPN and number of hospitalization days related to HPN, over a year; incidence of line sepsis per 1000 catheter days and mortality. Data are presented as median (1st, 3rd quartile) for continuous variables and frequency (percentage) for categorical variables. Comparisons between groups were performed using two sample t-test or Wilcoxon Rank Sum tests for continuous variables and Chi-square tests or Fisher's exact tests for categorical variables. Univariate and multiple linear regressions were also carried out. Statistical significance is set at a p-value <0.05. RESULTS: A total of 120 patients were included (MO n = 68, SO n = 52). Significant differences at baseline between the two groups were a higher use of Hickman line (62.12% vs 42%, p = 0.038) and more western Canada based hospital care with MO (75% vs 42.31%, p = 0.0002). The MO group had significantly more hospitalizations (p = 0.001), more hospitalizations related to HPN (p = 0.012) and more hospitalization days related to HPN (p = 0.016) per patient per year compared to SO patients. There was no significant difference between groups for line sepsis per 1000 catheter days (MO: 0.05 (0.0, 1.0) vs SO: 0.0 (0.0, 0.22), p = 0.053) or mortality. All other variables, including biochemical variables, were similar between groups. In a multiple regression analysis, the following factors were significantly associated with a greater number of hospitalizations per patient per year: use of MO, high blood glucose from the last recorded value and having died by the end of the study period. CONCLUSION: This 2-year prospective cohort study suggests an increased risk of hospitalization in HPN patients receiving MO lipid emulsion. The long-term effect of using MO lipid emulsion in HPN patients should be further evaluated using a large randomized controlled trial. THE STUDY WAS REGISTERED IN CLINICALTRIALS.GOV: (NCT02299466).

Timing of Tributyrin Supplementation Differentially Modulates Gastrointestinal Inflammation and Gut Microbial Recolonization Following Murine Ileocecal Resection.

BACKGROUND: Gastrointestinal surgery imparts dramatic and lasting imbalances, or dysbiosis, to the composition of finely tuned microbial ecosystems. The aim of the present study was to use a mouse ileocecal resection (ICR) model to determine if tributyrin (TBT) supplementation could prevent the onset of microbial dysbiosis or alternatively enhance the recovery of the gut microbiota and reduce gastrointestinal inflammation. METHODS: Male wild-type (129 s1/SvlmJ) mice aged 8-15 weeks were separated into single cages and randomized 1:1:1:1 to each of the four experimental groups: control (CTR), preoperative TBT supplementation (PRE), postoperative TBT supplementation (POS), and combined pre- and postoperative supplementation (TOT). ICR was performed one week from baseline assessment with mice assessed at 1, 2, 3, and 4 weeks postoperatively. Primary outcomes included evaluating changes to gut microbial communities occurring from ICR to 4 weeks. RESULTS: A total of 34 mice that underwent ICR (CTR n = 9; PRE n = 10; POS n = 9; TOT n = 6) and reached the primary endpoint were included in the analysis. Postoperative TBT supplementation was associated with an increased recolonization and abundance of anaerobic taxa including Bacteroides thetaiotomicorn, Bacteroides caecimuris, Parabacteroides distasonis, and Clostridia. The microbial recolonization of PRE mice was characterized by a bloom of aerotolerant organisms including Staphylococcus, Lactobacillus, Enteroccaceae, and Peptostreptococcacea. PRE mice had a trend towards decreased ileal inflammation as evidenced by decreased levels of IL-1ß (p = 0.09), IL-6 (p = 0.03), and TNF-α (p < 0.05) compared with mice receiving TBT postoperatively. In contrast, POS mice had trends towards reduced colonic inflammation demonstrated by decreased levels of IL-6 (p = 0.07) and TNF-α (p = 0.07). These changes occurred in the absence of changes to fecal short-chain fatty acid concentrations or histologic injury scoring. CONCLUSIONS: Taken together, the results of our work demonstrate that the timing of tributyrin supplementation differentially modulates gastrointestinal inflammation and gut microbial recolonization following murine ICR.

Triglyceride regulate ACE2 level through MTHFD1.

Obesity has been followed with interest as a risk factor for COVID-19, with triglycerides as one of four common criteria used to define obesity, which have been used to study the mechanism of obesity. In this study, we showed that angiotensin-converting enzyme-2 (ACE2) is widely expressed in the mouse body, including the kidney, spleen, brain, heart, lung, liver, and testis, and that ACE2 levels increased after a high-fat diet. The ACE2 levels were recorded at 0 days, 3 days, 7 days, and 14 days after a high-fat diet, and they increased at 14 days after high-fat diet initiation. In addition, triglyceride levels were also significantly increased at 14 days after high-fat diet initiation, but body weight was not changed. Furthermore, we examined the ACE2 levels in Calu3 cells (a lung cancer cell line) after triglyceride treatment, and the results indicated that ACE2 levels were increased at 25 µM and reached their peak at 200 µM. Finally, we found that the mRNA level of mthfd1 was significantly increased in the high-fat diet group. Given these findings, we hypothesize that triglycerides can regulate the expression of ACE2 and Mthfd1.

[A case of adult-onset type II citrullinemia triggered by entering a nursing home with a good response to medium-chain triglyceride oil therapy].

A 49-year-old woman with intellectual disability and a food preference for fried chicken entered a nursing home. After nursing home diet, she developed episodic attacks of hyperammonemic encephalopathy. Her characteristic food preference and the negative results for brain and liver imaging studies suggested urea cycle disorder. A high plasma citrulline level on amino acid analysis and a genetic test for citrine gene confirmed a citrine deficiency (adult-onset type II citrullinemia). Although a low-carbohydrate diet was insufficient, a combination therapy of a low-carbohydrate diet and a medium-chain triglyceride (MCT) oil was effective. MCT oil may be a promising treatment option.

Assessing the Impact of Factors that Influence the Ketogenic Response to Varying Doses of Medium Chain Triglyceride (MCT) Oil.

Objectives, Design, Setting: The ketogenic effect of medium chain triglyceride (MCT) oil offers potential for Alzheimer's disease prevention and treatment. Limited literature suggests a linear B-hyroxybutyrate (BHB) response to increasing MCT doses. This pharmacokinetic study evaluates factors affecting BHB response in three subject groups. PARTICIPANTS: Healthy subjects without cognitive deficits <65years, similarly healthy subjects >=65years, and those with Alzheimer's Disease were assessed. INTERVENTION: Different doses (0g,14g, 28g, 42g) of MCT oil (99.3% C8:0) were administered, followed by fasting during the study period. MEASUREMENTS: BHB measured by finger prick sampling hourly for 5 hours after ingestion. Each subject attended four different days for each ascending dose. Data was also collected on body composition, BMI, waist/hip ratio, grip strength, gait speed, nutrient content of pre-study breakfast and side effects. RESULTS: Twenty-five participants: eight healthy; average age of 44yr (25-61), nine healthy; 79yr (65-90) and eight with AD; 78.6yr (57-86) respectively. Compiled data showed the expected linear dose response relationship. No group differences, with baseline corrected area under the blood vs. time curve (r2=0.98) and maximum concentrations (r2=0.97). However, there was notable individual variability in maximum BHB response (42g dose: 0.4 -2.1mM), and time to reach maximum BHB response both, within and between individuals. Variability was unrelated to age, sex, sarcopenic or AD status. Visceral fat, BMI, waist/hip ratio and pretest meal CHO and protein content all affected the BHB response (p<0.001). CONCLUSION: There was a large inter-individual variability, with phenotype effects identified. This highlights challenges in interpreting clinical responses to MCT intake.

Administration of an Intravenous Fat Emulsion Enriched with Medium-Chain Triglyceride/ω-3 Fatty Acids is Beneficial Towards Anti-Inflammatory Related Fatty Acid Profile in Preterm Neonates: A Randomized, Double-Blind Clinical Trial.

Intravenous administration of pure soybean oil emulsions high in linoleic acid may lead to inflammation and lipid peroxidation in preterm neonates. We aimed to investigate the effects of a medium-chain triglyceride (MCT)/ω-3 polyunsaturated fatty acid (PUFA)-enriched intravenous fat emulsion (IVFE) on plasma fatty acid (FA) profile and serum interleukin-6 (IL-6) in preterm neonates. In this double-blind randomized study, 92 preterm neonates (gestational age < 32 weeks, birth weight < 1500 g) were assigned to receive either MCT/ω-3 PUFA-enriched IVFE (Intervention Group) or soybean oil-based IVFE (Control Group). Levels of FAs were measured at baseline (day 0) and day 15 of parenteral nutrition with gas-chromatography mass-spectrometry. Serum IL-6 was measured with sandwich ELISA in 59 neonates. Plasma FAs changed significantly over time; the MCT/ω-3 PUFA-IVFE group showed higher ω-3 PUFAs (p = 0.031), eicosapentaenoic acid (p = 0.000), and oleic acid (p = 0.003), and lower ω-6/ω-3 PUFAs ratio (p = 0.001) and ω-6 PUFAs (p = 0.023) compared to control group. Linoleic acid was higher in the soybean oil (SO)-based IVFE arm compared to the MCT/ω-3 PUFAs-IVFE arm (p = 0.006). Both fat emulsion types decreased IL-6 compared to baseline, but changes were insignificant between groups. Administration of MCT/ω-3 PUFA-enriched IVFE in preterm neonates is beneficial in changing the FA profile consistent with attenuated inflammatory response.

Management of large congenital chylous ascites in a preterm infant: fetal and neonatal interventions.

Congenital chylous ascites is a rare cause of ascites in newborn infants. Its aetiology varies from localised leaky lymphatic duct to genetic syndromes. Most of these cases have transient ascites resolving over time with conservative management but some may progress needing medical as well as surgical treatment. We describe a case of antenatally detected large fetal ascites necessitating abdominal paracentesis and amnioreduction. Marked respiratory distress at birth required urgent abdominal paracentesis to relieve symptoms. The infant initially showed a good response to medium chain triglyceride (MCT) based formula milk feeds. Feeds were discontinued for 3 weeks due to sepsis with ileus. On recovery, recommencement of feeds resulted in reaccumulation of ascites. As the response to MCT-based formula was inadequate, octreotide therapy was initiated. Ascites showed remarkable resolution over the next 2 weeks and was discharged home. Follow-up at 5 years of age revealed normal growth and neurodevelopment.

Delayed Presentation of Meconium Ileus in an Infant With Cystic Fibrosis.

Although infants with meconium ileus usually present with apparent symptoms shortly after birth, the diagnosis of meconium ileus and cystic fibrosis (CF) may be delayed, awaiting newborn screening (NBS) results. We present the case of an 11-day-old term girl with delayed passage of meconium at 48 hours who had 2 subsequent small meconium stools over the following week. There was a normal feeding history and no signs of abdominal distension or distress. She then presented with an acute abdomen, decompensated shock, bowel perforation, and peritonitis, requiring multiple intestinal surgeries. Her NBS for CF was positive, and CF was ultimately confirmed with mutation analysis. Her course was complicated by prolonged parenteral feedings and mechanical ventilation via tracheostomy. The infant was managed with soy oil, medium chain triglycerides, olive oil, fish oil lipids and experienced only transaminitis without cholestasis and no chronic liver sequelae, with subsequent normalization of her transaminases without treatment. Because her only symptom was decreased stool output and NBS results were unavailable, the CF diagnosis was delayed until she presented in extremis. Delayed meconium passage and decreased stool output during the first week of life should lead to suspicion and additional evaluation for CF while awaiting NBS results. Careful monitoring is indicated to prevent serious, life-threatening complications. The use of soy oil, medium chain triglycerides, olive oil, fish oil lipids for infants requiring prolonged parenteral nutrition may also be considered proactively to prevent cholestasis, particularly for high risk groups.

Effects of supplementing Holstein cows with soybean oil compared with palmitic acid-enriched triglycerides on milk production and nutrient partitioning.

Both insulin and trans-10,cis-12 C18:2 (t10c12CLA) can be increased by high-starch diets; thus, it is difficult to determine whether insulin or t10c12CLA mediates nutrient partitioning toward body tissues during milk fat depression. To minimize insulin secretion while manipulating t10c12CLA levels, diets supplemented with palmitic acid-enriched triglycerides and soybean oil were fed to cows. Thirty-two Holstein cows (93 ± 35 d in milk) were included in the crossover experiment with each treatment period being 28 d. Treatment diets contained 25% neutral detergent fiber, 32% starch, 18% crude protein, and 4.6% fatty acids (dry matter basis). Treatment diets contained either palmitic acid-enriched triglycerides (2.5% dry matter, BergaFat T-300, Berg + Schmidt America LLC, Libertyville, IL; PAT) or soybean oil (2.5% dry matter; SBO). Cows were blocked by milk yield, body weight, and parity, and then randomly assigned to 1 of 2 treatment sequences (PAT-SBO or SBO-PAT). Cows fed PAT produced milk with only 3.1% fat, indicating milk fat depression; SBO decreased fat content further to only 2.4%. No effect of treatment was observed on dry matter intake, apparent net energy intake, milk yield, body condition score, or fat thickness over the rump and rib. However, compared with PAT, SBO decreased fat-corrected milk yield, energy-corrected milk yield, milk fat yield, de novo fatty acids, and 16-carbon fatty acid yield, whereas SBO increased body weight gain. Neutral detergent fiber digestibility tended to be lower in SBO, whereas fatty acid digestibility was higher. Additionally, the concentration of plasma insulin, nonesterified fatty acids, and triglycerides, and milk metabolites (trans-10 C18:1 and t10c12CLA) were all higher in SBO. In conclusion, with similar dietary starch content, the diet containing palmitic acid-enriched triglycerides partitioned more energy toward milk synthesis, whereas the diet containing soybean oil partitioned more energy toward body tissue gain.

Omega-3 Phospholipids from Krill Oil Enhance Intestinal Fatty Acid Oxidation More Effectively than Omega-3 Triacylglycerols in High-Fat Diet-Fed Obese Mice.

Antisteatotic effects of omega-3 fatty acids (Omega-3) in obese rodents seem to vary depending on the lipid form of their administration. Whether these effects could reflect changes in intestinal metabolism is unknown. Here, we compare Omega-3-containing phospholipids (krill oil; ω3PL-H) and triacylglycerols (ω3TG) in terms of their effects on morphology, gene expression and fatty acid (FA) oxidation in the small intestine. Male C57BL/6N mice were fed for 8 weeks with a high-fat diet (HFD) alone or supplemented with 30 mg/g diet of ω3TG or ω3PL-H. Omega-3 index, reflecting the bioavailability of Omega-3, reached 12.5% and 7.5% in the ω3PL-H and ω3TG groups, respectively. Compared to HFD mice, ω3PL-H but not ω3TG animals had lower body weight gain (-40%), mesenteric adipose tissue (-43%), and hepatic lipid content (-64%). The highest number and expression level of regulated intestinal genes was observed in ω3PL-H mice. The expression of FA ω-oxidation genes was enhanced in both Omega-3-supplemented groups, but gene expression within the FA ß-oxidation pathway and functional palmitate oxidation in the proximal ileum was significantly increased only in ω3PL-H mice. In conclusion, enhanced intestinal FA oxidation could contribute to the strong antisteatotic effects of Omega-3 when administered as phospholipids to dietary obese mice.

Emulsion Droplet Crystallinity Attenuates Short-Term Satiety in Healthy Adult Males: A Randomized, Double-Blinded, Crossover, Acute Meal Study.

BACKGROUND: The influence of triacylglycerol (TAG) physical properties on satiety remains poorly understood. OBJECTIVES: The objective was to investigate if and how TAG digestion and absorption, modulated only by differences in TAG crystallinity, would differentially affect short-term satiety in healthy men. METHODS: We tempered 500 mL 10% palm stearin oil-in-water emulsions such that the lipid droplets were either undercooled liquid (LE) or partially crystalline solid (SE). Fifteen healthy men (mean ± SD age: 27.5 ± 5.7 y; BMI: 24.1 ± 2.5 kg/m2; fasting TAG: 0.9 ± 0.3 mmol/L) consumed each beverage at two 6-h study visits separated by ≥6 d after an overnight fast, along with 1500 mg acetaminophen suspended in water. The participants characterized the emulsion sensory properties, completed satiety visual analog scale ratings, and had serial blood samples collected for 6-h analysis of plasma peptide YY (PYY), glucagon-like peptide-1 (GLP-1), ghrelin, leptin, glucose-dependent insulinotropic polypeptide (GIP), insulin, and acetaminophen (for assessing gastric emptying). Repeated-measures ANOVAs and 2-tailed paired t tests were used to analyze the changes from baseline and incremental area under the curve (iAUC) values, respectively. RESULTS: With consumption of LE compared with SE, there was a 358% higher fullness (P = 0.015) and a 103% lower average appetite (P = 0.041) score, along with higher iAUC values for PYY (P = 0.011) and GLP-1 (P = 0.028) (103% and 66% higher, respectively), but not for ghrelin (P = 0.39), based on change from baseline values. Acetaminophen response trended toward significance (P = 0.08) and was 15% higher with LE. SE was rated as 44% thicker (P = 0.034) and 24% creamier (P = 0.05) than LE. CONCLUSIONS: The suppression of TAG digestion by the presence of partially crystalline lipid droplets blunted the appetite-suppressing effects of an oil-in-water emulsion.This trial was registered at clinicaltrials.gov as NCT03990246.

Relationship between redox potential of glutathione and DNA methylation level in liver of newborn guinea pigs.

The metabolism of DNA methylation is reported to be sensitive to oxidant molecules or oxidative stress. Hypothesis: early-life oxidative stress characterized by the redox potential of glutathione influences the DNA methylation level. The in vivo study aimed at the impact of modulating redox potential of glutathione on DNA methylation. Newborn guinea pigs received different nutritive modalities for 4 days: oral nutrition, parenteral nutrition including lipid emulsion Intralipid (PN-IL) or SMOFLipid (PN-SF), protected or not from ambient light. Livers were collected for biochemical determinations. Redox potential (p < 0.001) and DNA methylation (p < 0.01) were higher in PN-infused animals and even higher in PN-SF. Their positive correlation was significant (r2 = 0.51; p < 0.001). Methylation activity was higher in PN groups (p < 0.01). Protein levels of DNA methyltransferase (DNMT)-1 were lower in PN groups (p < 0.01) while those of both DNMT3a isoforms were increased (p < 0.01) and significantly correlated with redox potential (r2 > 0.42; p < 0.001). The ratio of SAM (substrate) to SAH (inhibitor) was positively correlated with the redox potential (r2 = 0.36; p < 0.001). In conclusion, early in life, the redox potential value strongly influences the DNA methylation metabolism, resulting in an increase of DNA methylation as a function of increased oxidative stress. These results support the notion that early-life oxidative stress can reprogram the metabolism epigenetically. This study emphasizes once again the importance of improving the quality of parenteral nutrition solutions administered early in life, especially to newborn infants. Abbreviation of Title: Parenteral nutrition and DNA methylation.

Efficacy of medium chain triglyceride oil dietary supplementation in reducing seizure frequency in dogs with idiopathic epilepsy without cluster seizures: a non-blinded, prospective clinical trial.

BACKGROUND: Despite appropriate antiseizure drug (ASD) treatment, around two-thirds of dogs with idiopathic epilepsy (IE) have seizures long-term and 20-30per cent of affected dogs remain poorly controlled. METHODS: The current study aim is to test in a field trial the efficacy and tolerability of a commercially available diet enriched with 6.5per cent medium chain triglyceride (MCT) oil in dogs (n=21) with at least a tier 1 idiopathic epilepsy diagnosis, without cluster seizures, in 10 veterinary practices across Europe. Each dog's quality of life (QoL), ataxia, sedation and frequency and severity of seizures were recorded by owners throughout the study. RESULTS: The mean seizure frequency per month, averaged over the entire 84-day study, significantly (P=0.04) decreased 32per cent compared with the baseline monthly seizure frequency recorded during the month immediately before feeding the diet. Similarly, the seizure days rate (days/month) also declined (P<0.001) by 42per cent. QoL was reported as very good to excellent (>8.5/10) in 20 of the 21 dogs before starting the diet and this remained unchanged during the trial. CONCLUSIONS: This study demonstrates the use of a diet enriched with MCTs as an adjunct to ASD treatment may have some antiseizure properties for dogs diagnosed with IE, as demonstrated in previous studies.

Gender differences on oxidative stress markers and complement component C3 plasma values after an oral unsaturated fat load test.

OBJECTIVE: Post-prandial lipaemia (PL), oxidative stress (OS), and complement component C3 (C3) values are related to the atherosclerosis process. The post-prandial response of C3 after an oral fat load test (OFLT) using unsaturated fat is poorly addressed. The aim of this study was to analyze and compare the post-prandial response of OS markers and C3 values in men and women after an OFLT using unsaturated fat. METHODS: The study included a total of 22 healthy subjects with normal lipids and normal blood glucose (11 men and 11 pre-menopausal women). An oral unsaturated fat load test (OFLT: 50g fat per m2 body surface) was performed using a commercial liquid preparation of long chain triglycerides (Supracal®). OS markers and C3 were measured using standardized methods at fasting state and every 2h up to 8h after the OFLT. RESULTS: Men showed statistically significant higher C3, oxidized glutathione (GSSG), and oxidized-reduced glutathione (GSSG/GSH) ratio values at fasting state compared to that obtained in women. In addition, post-prandial C3 values and GSSG/GSH ratios were significantly higher in men compared to women. The GSSG value and GSSG/GSH ratio significantly decreased in men after the OFLT compared to fasting values. In contrast, the post-prandial OS markers decrease observed in women was not statistically significant. CONCLUSIONS: In fasting state, men showed higher statistically significant C3 values and OS markers than women. The post-prandial OS markers (GSSG and GSSG/GSH ratio) significantly decrease after the OFLT with unsaturated fat in men compared to women.

Docosahexaenoate-enriched fish oil and medium chain triglycerides shape the feline plasma lipidome and synergistically decrease circulating gut microbiome-derived putrefactive postbiotics.

The purpose of this study was to examine the influence of medium-chain fatty acid-containing triglycerides (MCT), long-chain polyunsaturated fatty acid-containing triglycerides, and their combination on the plasma metabolome of cats (Felis catus), including circulating microbiome-derived postbiotics. After a 14-day lead-in on the control food, cats were randomized to one of four foods (control, with 6.9% MCT, with fish oil [FO; 0.14% eicosapentaenoate, 1.0% docosahexaenoate], or with FO+MCT; n = 16 per group) for 28 days. Analysis of plasma metabolites showed that the addition of FO and MCT led to synergistic effects not seen with either alone across a number of lipid classes, including fatty acids, acylcarnitines, and acylated amines including endocannabinoids. Notably, the FO+MCT group had an increase in ketone body production relative to baseline and beyond that seen with MCT alone. N-acyl taurines, the accumulation of which has been implicated in the onset of type 2 diabetes, were significantly decreased in the FO+MCT group. Significant decreases in the gut microbiome-derived postbiotic classes of indoles/indolic sulfates and phenols/phenolic sulfates were observed only the FO+MCT group. Overall, the combination of MCT and FO led to number of changes in plasma metabolites that were not observed with either oil alone, particularly in postbiotics.

Cardiac tissue citric acid cycle intermediates in exercised very long-chain acyl-CoA dehydrogenase-deficient mice fed triheptanoin or medium-chain triglyceride.

Anaplerotic odd-chain fatty acid supplementation has been suggested as an approach to replenish citric acid cycle intermediate (CACi) pools and facilitate adenosine triphosphate (ATP) production in subjects with long-chain fatty acid oxidation disorders, but the evidence that cellular CACi depletion exists and that repletion occurs following anaplerotic substrate supplementation is limited. We exercised very long-chain acyl-CoA dehydrogenase-deficient (VLCAD-/-) and wild-type (WT) mice to exhaustion and collected cardiac tissue for measurement of CACi by targeted metabolomics. In a second experimental group, VLCAD-/- and WT mice that had been fed chow prepared with either medium-chain triglyceride (MCT) oil or triheptanoin for 4 weeks were exercised for 60 minutes. VLCAD-/- mice exhibited lower succinate in cardiac muscle at exhaustion than WT mice suggesting lower CACi in VLCAD-/- with prolonged exercise. In mice fed either MCT or triheptanoin, succinate and malate were greater in VLCAD-/- mice fed triheptanoin compared to VLCAD-/- animals fed MCT but lower than WT mice fed triheptanoin. Long-chain odd acylcarnitines such as C19 were elevated in VLCAD-/- and WT mice fed triheptanoin suggesting some elongation of the heptanoate, but it is unknown what proportion of heptanoate was oxidized vs elongated. Prolonged exercise was associated with decreased cardiac muscle succinate in VLCAD-/- mice in comparison to WT mice. VLCAD-/- fed triheptanoin had increased succinate compared to VLCAD-/- mice fed MCT but lower than WT mice fed triheptanoin. Cardiac CACi were higher following dietary ingestion of an anaplerotic substrate, triheptanoin, in comparison to MCT.