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Increased lipid levels sometimes not only affect sexual function but also are considered to harm semen quality. It is often a suspicion that elevated lipids are a factor in infertility. We conduct a systematic review. Articles that met the criteria were identified according to The Preferred Reporting Items for Systematic Review and Meta-analysis of recommendations in the PubMed, ProQuest, EBSCO, Web of Science Wiley Online, Springer Link, Scopus, and Science Direct databases with no time restriction for publication. Seven studies are eligible for qualitative analysis from nine studies that have the potential to be assessed. These studies measure the correlation of serum lipids (VLDL, HDL, LDL, triglycerides, total cholesterol, free cholesterol, phospholipids, free fatty acids) with semen parameters (concentration, motility, morphology, DNA fragmentation index). Although not all studies consistently report that lipids impact semen quality, this review suspects that lipids have a significant impact on sperm quality. This study implies that it is necessary to maintain lipid levels to maintain sperm quality and quality of life. However, further investigation with an observational cohort study design needs to be carried out to assess the effect of lipids on semen quality more precisely for the promotion of reproductive health care., (© 2022. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Aim/introduction: Diabetes Mellitus is a chronic degenerative disease, and its main biochemical characteristic is hyperglycemia due to impaired insulin secretion, resistance to peripheral actions of insulin, or both. Hyperglycemia causes dyslipidemia and stimulates oxidative damage, leading to the main symptoms, such as fatigue and culminates in diabetic complications. Previous studies have shown that ATP-sensitive potassium channels counteract muscle fatigue and metabolic stress in healthy mouse models. To determine the effect of diazoxide on muscle strength development during diabetes, we tested the effect of diazoxide in streptozotocin-diabetic rats in muscle function, lipid profile and oxidative stress biomarkers., Materials and Methods: Wistar rats were divided into 4 groups of six animals each: (1) Control group, (2) diabetes group, (3) Control group + diazoxide, and (4) Diabetic + diazoxide (DB + DZX). 4 weeks after rats were sacrificed, soleus and extensor digitorum longus muscles (EDL) were extracted to prepare homogenates and serum was obtained for biochemical measurements. Oxidative damage was evaluated by the thiobarbituric acid method and the fluorescent for reactive oxygen species (ROS) probe 2,4-H 2 DCFDA, respectively., Results: Diabetic rats with diazoxide administration showed an increase in the development of muscle strength in both muscles; in turn, the onset of fatigue was longer compared to the group of diabetic rats without treatment. Regarding the lipid profile, diazoxide decreased total cholesterol levels in the group of diabetic rats treated with diazoxide (x̅46.2 mg/dL) compared to the untreated diabetic group (x̅=104.4 mg/dL); secondly, diazoxide decreased triglyceride concentrations (x̅=105.3 mg/dL) compared to the untreated diabetic rats (x̅=412.2 mg/dL) as well as the levels of very low-density lipoproteins (x̅=20.4 mg/dL vs. x̅=82.44 mg/dL). Regarding the various markers of oxidative stress, the diabetic group treated with diazoxide was able to reduce the concentrations of TBARS and total reactive oxygen species as well as preserve the concentrations of reduced glutathione., Conclusion: Diazoxide administration in diabetic rats increases muscle strength development in EDL and soleus muscle, decreases fatigue, reduces cholesterol and triglyceride concentrations and improves oxidative stress parameters such as TBARS, ROS, and glutathione status., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study investigated whether a 30-day co-treatment with 1 g/kg glutamine dipeptide (GdiP) and 1 U/kg regular (rapid acting) or 5 U/kg degludec (long acting) insulins modifies glucose homeostasis and liver metabolism of alloxan-induced type 1 diabetic (T1D) male Swiss mice undergoing insulin-induced hypoglycemia (IIH). Glycemic curves were measured in fasted mice after IIH with 1 U/kg regular insulin. One hour after IIH, the lipid profile and AST and ALT activities were assayed in the serum. Morphometric analysis was assessed in the liver sections stained with hematoxylin-eosin and glycolysis, glycogenolysis, gluconeogenesis and ureagenesis were evaluated in perfused livers. T1D mice receiving GdiP or the insulins had a smaller blood glucose drop at 60 minutes after IIH, which was not sustained during the subsequent period up to 300 minutes. The 30-day treatment of T1D mice with insulin degludec, but not with regular insulin, improved fasting glycemia, body weight gain and serum activity of AST and ALT. Treatments with insulin degludec, GdiP and insulin degludec + GdiP decreased the liver capacity in synthesizing glucose from alanine. GdiP, in combination with both insulins, was associated with increases in the serum triglycerides and, in addition, regular insulin and GdiP increased AST and ALT activities, which could be the consequence of hepatic glycogen overload. GdiP and the insulins improved the IIH, although to a small extent. Caution is recommended, however, with respect to the use of GdiP because of its increasing effects on serum triglycerides and AST plus ALT activities., Competing Interests: Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) had no involvement in the study design, the collection, analysis and interpretation of data, the writing of the report, nor the decision to submit the article for publication.

Background: Remnant cholesterol (RC) mediates the progression of coronary artery disease, diabetic complications, hypertension, and chronic kidney disease. Limited information is available on the association of RC with nonalcoholic fatty liver disease (NAFLD). This study aimed to explore whether RC can be used to independently evaluate the risk of NAFLD in the general population and to analyze the predictive value of RC for NAFLD., Methods: The study included 14,251 subjects enrolled in a health screening program. NAFLD was diagnosed by ultrasound, and the association of RC with NAFLD was assessed using the receiver operating characteristic (ROC) curve and logistic regression equation., Results: Subjects with elevated RC had a significantly higher risk of developing NAFLD after fully adjusting for potential confounding factors (OR 1.77 per SD increase, 95% CI 1.64-1.91, P trend< 0.001). There were significant differences in this association among sex, BMI and age stratification. Compared with men, women were facing a higher risk of RC-related NAFLD. Compared with people with normal BMI, overweight and obesity, the risk of RC-related NAFLD was higher in thin people. In different age stratifications, when RC increased, young people had a higher risk of developing NAFLD than other age groups. Additionally, ROC analysis results showed that among all lipid parameters, the AUC of RC was the largest (women: 0.81; men: 0.74), and the best threshold for predicting NAFLD was 0.54 in women and 0.63 in men., Conclusions: The results obtained from this study indicate that (1) in the general population, RC is independently associated with NAFLD but not with other risk factors. (2) Compared with traditional lipid parameters, RC has a better predictive ability for NAFLD in men., (© 2021. The Author(s).)

The incidence and mortality of hepatocellular carcinoma (HCC) are gradually increasing during the past years. Recently, some studies have reported that malic enzyme (ME) plays an important role in cancer development, while the involvement of ME2 in HCC remains still undetermined. Here, we demonstrated that ME2 played an oncogenic role in HCC. ME2 was overexpressed in HCC tissues. TCGA database showed that the ME2 transcript level was inversely associated with the survival of HCC patients. Loss-of-function and gain-of-function assays showed that ME2 promoted HCC cell growth and migration. Furthermore, the xenografted tumorigenesis of MHCC97H cells was retarded by ME2 knockdown. ME2 silencing also suppressed the cell cycle process and induced apoptosis. Mechanistically, ME2 potentiated triglyceride synthesis, inhibition of which suppressed the proliferation and migration. We propose that ME2 promotes HCC progression by increasing triglyceride production., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objective: This study aimed to establish neonatal serum triglyceride (TG) level reference ranges during lipid infusion and correlate peak TG with neonatal outcomes., Study Design: This is a retrospective review of 356 neonates with 696 TG measures obtained in four neonatal intensive care units between 2015 and 2017. TG was evaluated collectively to establish a reference range and a threshold limit. To analyze the effects of a higher TG threshold, neonates were categorized by their peak TG: <180 (TG <180 ), 180 to 400 (TG 180-400 ), and > 400 mg/dL (TG >400 ). Univariable and multivariable regression models were constructed to compare peak TG to patient characteristic and clinical outcomes., Results: The frequency of TG > 400 mg/dL was 5% and found only in neonates weighing < 1.5 kg. Neonates in the TG 180-400 ( n  = 91) group were significantly lower in birth weight and gestational age, had lower 5-minute APGAR scores, and had increased ventilatory requirement when compared with neonates in the TG <180 ( n  = 240) group (all p  < 0.001). The TG 180-400 group had increased risk of severe intraventricular hemorrhage ( p  = 0.02) and bronchopulmonary dysplasia ( p  = 0.03). Elevated TG was associated with mortality (odds ratio [OR]: 14.4, p  < 0.001) in univariable analysis, but the relationship weakened (OR: 4.4, p  = 0.05) after adjusting for comorbidities in multivariable logistic regression., Conclusion: It is unclear if the adverse outcomes seen in neonates with higher peak TG were due to elevated TG alone, or whether illness severity predicted the increased TG. More prospective studies are needed to further delineate the relationships., Competing Interests: None declared., (Thieme. All rights reserved.)

Ketogenic diet therapy (KDT), particularly modified Atkins diet (MAD), is increasingly recognized as a treatment for adults with epilepsy. Women with epilepsy (WWE) comprise 50% of people with epilepsy and approximately one in three have catamenial epilepsy. The purpose of this study was to determine whether adding a medium chain triglyceride emulsion to MAD to target catamenial seizures was feasible and well-tolerated. This was a prospective two-center study of pre-menopausal WWE with a catamenial seizure pattern on MAD. After a 1-month baseline interval with no changes in treatment, participants consumed betaquik ® (Vitaflo International Ltd.) for 10 days each menstrual cycle starting 2 days prior to and encompassing the primary catamenial seizure pattern for five cycles. Participants recorded seizures, ketones, and menses, and completed surveys measuring tolerability. Sixteen women aged 20-50 years (mean 32) were enrolled and 13 (81.2%) completed the study. There was 100% adherence for consuming betaquik ® in the women who completed the study and overall intervention adherence rate including the participants that dropped out was 81.2%. The most common side effects attributed to MAD alone prior to starting betaquik ® were constipation and nausea, whereas abdominal pain, diarrhea, and nausea were reported after adding betaquik ® . The high adherence rate and acceptable tolerability of betaquik ® shows feasibility for future studies evaluating KDT-based treatments for catamenial seizures.

Background: Lipaemic interference on automated analysers has been widely studied using soy-based emulsion such as Intralipid. Due to the greater adoption of fish oil-based lipid emulsion for total parenteral nutrition in view of improved clinical outcomes, we seek to characterize the optical properties of SMOFlipid 20% (Fresenius Kabi, Bad Homburg, Germany), a fish oil-based emulsion, on the Roche Cobas 6000 chemistry analyser (Roche Diagnostic, Basel, Switzerland)., Method: Various amounts of SMOFlipid were spiked into pooled serums. We plotted Roche Cobas Serum Index Gen.2 Lipaemia Index (L-index) against the amount of SMOFlipid added. We then studied the interference thresholds for aspartate aminotransferase, alanine aminotransferase, albumin and renal panel analytes using SMOFlipid. We subjected five levels of spiked lipaemia to high-speed centrifugation and analysed the specimens pre- and post-centrifugation. To postulate whether fish oil-based lipid emulsion interferes with laboratory results in the clinical setting, we calculated concentrations of SMOFlipid post-lipid rescue therapy and steady-state concentration of a typical total parenteral nutrition regime using pharmacokinetic principles., Results: SMOFlipid optical behaviour is similar to Intralipid using the Serum Index Gen.2 L-index, with 1 mg/dL of SMOFlipid representing 1 unit of L-index. Manufacturer-stated interference thresholds are accurate for alanine aminotransferase, aspartate aminotransferase, albumin, urea and creatinine. High-speed centrifugation at 60 min 21,100 g facilitates the removal of fish oil-based SMOFlipid., Conclusion: Based on the interference thresholds we verified and pharmacokinetics parameters provided by SMOFlipid manufacturer, total parenteral nutrition may not interfere with chemistry analytes given sufficient clearance, but lipid rescue therapy will interfere. Further studies assessing lipaemic interference on immunoassays are needed.

Background: In-hospital growth of preterm infants remains a challenge in clinical practice. The high nutrient demands of preterm infants often lead to growth faltering. For preterm infants who cannot be fed maternal or donor breast milk or may require supplementation, preterm formulas with fat in the form of medium chain triglycerides (MCTs) or long chain triglycerides (LCTs) may be chosen to support nutrient utilization and to improve growth. MCTs are easily accessible to the preterm infant with an immature digestive system, and LCTs are beneficial for central nervous system development and visual function. Both have been incorporated into preterm formulas in varying amounts, but their effects on the preterm infant's short-term growth remain unclear. This is an update of a review originally published in 2002, then in 2007., Objectives: To determine the effects of formula containing high as opposed to low MCTs on early growth in preterm infants fed a diet consisting primarily of formula.  SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 8), in the Cochrane Library; Ovid MEDLINE Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily, and Ovid MEDLINE(R); MEDLINE via PubMed for the previous year; and Cumulative Index to Nursing and Allied Health Literature (CINAHL), on 16 September 2020. We also searched clinical trials databases and the reference lists of retrieved articles for randomized controlled trials (RCTs) and quasi-RCTs., Selection Criteria: We included all randomized and quasi-randomized trials comparing the effects of feeding high versus low MCT formula (for a minimum of five days) on the short-term growth of preterm (< 37 weeks' gestation) infants. We defined high MCT formula as 30% or more by weight, and low MCT formula as less than 30% by weight. The infants must be on full enteral diets, and the allocated formula must be the predominant source of nutrition., Data Collection and Analysis: The review authors assessed each study's quality and extracted data on growth parameters as well as adverse effects from included studies. All data used in analysis were continuous; therefore, mean differences with 95% confidence intervals were reported. We used the GRADE approach to assess the certainty of evidence., Main Results: We identified 10 eligible trials (253 infants) and extracted relevant growth data from 7 of these trials (136 infants). These studies were found to provide evidence of very low to low certainty. Risk of bias was noted, as few studies described specific methods for random sequence generation, allocation concealment, or blinding. We found no evidence of differences in short-term growth parameters when high and low MCT formulas were compared. As compared to low MCT formula, preterm infants fed high MCT formula showed little to no difference in weight gain velocity (g/kg/d) during the intervention, with a typical mean difference (MD) of -0.21 g/kg/d (95% confidence interval (CI) -1.24 to 0.83; 6 studies, 118 infants; low-certainty evidence). The analysis for weight gain (g/d) did not show evidence of differences, with an MD of 0.00 g/d (95% CI -5.93 to 5.93; 1 study, 18 infants; very low-certainty evidence), finding an average weight gain of 20 ± 5.9 versus 20 ± 6.9 g/d for high and low MCT groups, respectively. We found that length gain showed no difference between low and high MCT formulas, with a typical MD of 0.10 cm/week (95% CI -0.09 to 0.29; 3 studies, 61 infants; very low-certainty evidence). Head circumference gain also showed little to no difference during the intervention period, with an MD of -0.04 cm/week (95% CI -0.17 to 0.09; 3 studies, 61 infants; low-certainty evidence). Two studies reported skinfold thickness with different measurement definitions, and evidence was insufficient to determine if there was a difference (2 studies, 32 infants; very low-certainty evidence). There are conflicting data (5 studies) as to formula tolerance, with 4 studies reporting narrative results of no observed clinical difference and 1 study reporting higher incidence of signs of gastrointestinal intolerance in high MCT formula groups. There is no evidence of effect on the incidence of necrotizing enterocolitis (NEC), based on small numbers in two trials. Review authors found no studies addressing long-term growth parameters or neurodevelopmental outcomes., Authors' Conclusions: We found evidence of very low to low certainty suggesting no differences among short-term growth data for infants fed low versus high MCT formulas. Due to lack of evidence and uncertainty, neither formula type could be concluded to improve short-term growth outcomes or have fewer adverse effects. Further studies are necessary because the results from included studies are imprecise due to small numbers and do not address important long-term outcomes. Additional research should aim to clarify effects on formula tolerance and on long-term growth and neurodevelopmental outcomes, and should include larger study populations to better evaluate effect on NEC incidence., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Introduction: Introduction: a lipid emulsion (LE) may result in different immunomodulatory effects depending on its fatty acid composition. LEs enriched with fish oil and those based on olive oil (OOBE) have shown advantages over those derived from soybean oil, although very few studies have compared these with each other, and none was performed in critically ill surgical patients. Objectives: to demonstrate non-inferiority for the therapeutic efficacy of SMOFlipid® (enriched with fish oil) versus Clinoleic® (OOBE) in relation to the occurrence of nosocomial infection and other evolutionary parameters. To demonstrate non-inferiority in the safety profile of SMOFlipid® versus Clinoleic® in terms of mortality and adverse events. Material and method: a phase-III, non-inferiority clinical trial performed in critically ill postsurgical patients. The subjects were randomized to receive SMOFlipid® or Clinoleic®. For comparison of qualitative variables case frequencies and percentages were obtained using the Chi-squared test or Fisher's exact test. Means were compared between groups using Student's t-test. A p-value lower than 0.05 was considered statistically significant. The Farrington-Manning, Miettinen-Nurminen, and Gart-Nam tests were applied in the main non-inferiority analysis of the primary endpoint. Results: during de inclusion period 73 patients were selected, 37 of whom received Clinoleic® and 36 SMOFlipid®. Regarding the variable "decrease in nosocomial infections", SMOFlipid® proved to be non-inferior to Clinoleic®. Regarding the main variable "mortality", SMOFlipid® proved to be non-inferior to Clinoleic®. There were no statistically significant differences in the occurrence of adverse effects either. Conclusions: in our study, SMOFlipid® proved to be non-inferior to Clinoleic® in terms of efficacy and safety.

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., Competing Interests: Angela G Juby, Dion R Brocks, David A Jay, Christopher MJ Davis, Diana R Mager, all have no conflicts of interest with respect to this study.

Background: The triglyceride glucose (TyG) index is an inexpensive clinical surrogate marker for insulin resistance. However, the relationship between TyG index and atherosclerotic cardiovascular disease (CVD) remains unclear. We evaluated the relationship between TyG index and CVD using a large-scale population dataset from the National Health Information Database (NHID)., Methods: We performed a retrospective observational cohort study of 5,593,134 persons older than 40 years from 2009 to 2017 using the NHID. We divided the participants into TyG index quartiles. Outcome variables were stroke, myocardial infarction, and both. The incidence of outcomes was estimated for each TyG quartile over the total follow-up period. All outcomes were analyzed by Cox proportional hazards regression analysis while controlling for baseline covariates., Results: During 8.2 years of mean follow-up, stroke was diagnosed in 89,120 (1.59%), MI in 62,577 (1.12%), and both stroke and MI in 146,744 (2.62%) participants. Multivariate-adjusted hazard ratios (HRs) for patients in the highest TyG index quartile demonstrated that these patients were at higher risk for stroke (HR = 1.259; 95% confidence interval [CI] 1.233-1.286), for MI (HR = 1.313; 95% CI 1.28-1.346), and for both (HR = 1.282; 95% CI 1.261-1.303) compared with participants in the lowest TyG index quartile. These effects were independent of age, sex, smoking, alcohol consumption, physical activity, body mass index, systolic blood pressure, and total cholesterol., Conclusions: In our large population study, TyG index, a simple measure reflecting insulin resistance, was potentially useful in the early identification of individuals at high risk of experiencing a cardiovascular event.

Triheptanoin (Dojolvi™), a synthetic medium-chain triglyceride, is being developed by Ultragenyx Pharmaceutical as a pharmaceutical-grade anaplerotic compound for use in the treatment of inherited metabolic disorders. In June 2020, triheptanoin received its first regulatory approval, in the USA, for use as a source of calories and fatty acids for the treatment of pediatric and adult patients with molecularly confirmed long-chain fatty acid oxidation disorders (LC-FAOD). Triheptanoin has also been investigated for use as a treatment in a range of other metabolic disorders or other diseases where energy deficiency is implicated. This article summarizes the milestones in the development of triheptanoin leading to this first regulatory approval for use in the treatment of pediatric and adult patients with LC-FAOD.

Background: Previous clinical and animal studies suggested that medium-chain triglycerides (MCT) might be an alternative energy substrate for the brain and might benefit patients with Alzheimer's disease (AD), but the clinical evidence is not substantial or totally convincing., Objective: To investigate the effects of MCT on cognitive ability in patients with mild to moderate AD and explore the changes in peripheral blood metabolomics., Methods: A double-blind, randomized, placebo-controlled crossover study was undertaken in 53 mild to moderate AD patients. Participants were randomized between two sequences (placebo followed by MCT or MCT followed by placebo) and took MCT jelly or placebo jelly (canola oil) by mouth three times daily (total daily fat dose: 17.3 g MCT, or 19.7 g canola oil) for 30 days per phase. The primary outcome was cognition as measured by the Alzheimer's Disease Assessment Scale-Cognitive Subscale, Chinese version (ADAS-Cog-C). The secondary outcome was self-care as measured by the activities of daily living scale (ADL) and changes in plasma metabolites., Results: This study showed a significant (p < 0.01) reduction in ADAS-Cog-C scores between the MCT (2.62 points below baseline) and placebo interventions (2.57 points above baseline). Data from 46 (86.8%) APOE4 -/- subjects who completed the entire study were analyzed. Changes in ADL scores were not significantly different between the MCT and placebo interventions (p > 0.05). The concentrations of TC, HDL-C, β-hydroxybutyrate and acetoacetate were significantly higher in the MCT group than in the placebo group (p < 0.05). Lysophosphatidylcholine 16:0 (LysoPC (16:0)), LysoPC (P-18:0), LysoPC (P-18:1(9Z)), LysoPC (20:2(11Z,14Z)), and LysoPC (22:5(4Z,7Z,10Z,13Z,16Z)) were significantly increased after MCT intervention, and the concentrations of LysoPC (18:0), palmitic acid, linoleic acid, oleic acid, and 7,12-dimethylbenz[a]anthracene were significantly decreased (p < 0.05), whereas no significant changes appeared after the placebo intervention. Androstenedione concentration increased after placebo intervention. Furthermore, a significant negative correlation was observed between changes in LysoPC (P-18:1(9Z)) and ADAS-Cog-C scores after MCT intervention (r = -0.1472, p < 0.05)., Conclusions: MCT had positive effects on cognitive ability in mild to moderate AD patients with APOE4 -/- . These effects of MCT might be related to the metabolism of LysoPC, oleic acid, linoleic acid and palmitic acid, in addition to the ketogenic effect., Study Id Number: ChiCTR-IOR-16009737., Registry Website: WHO ICTRP Search Portal - http://apps.who.int/trialsearch/Default.aspx., (Copyright © 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Aims: Serum triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio is known to be associated with cardiometabolic diseases. This study is aimed to evaluate the association between the TG/HDL-C ratio and incident type 2 diabetes with a large-sample, community-based Korean cohort over 12 years., Methods: Among 10,038 participants, a total of 8655 participants aged 40 to 69 years without diabetes were selected from the Korean Genome and Epidemiology Study (KoGES). The baseline TG/HDL-C ratio was divided into quartiles. Newly developed type 2 diabetes was defined by any of the following: a fasting plasma glucose level ≥ 126 mg/dL; a glucose level ≥ 200 mg/dL 2-hours after a 75 g oral glucose tolerance test; an HbA1c ≥ 6.5%; or treatment with anti-diabetic therapy. The hazard ratios (HRs) with 95% confidence intervals (CIs) for incident type 2 diabetes were calculated using multivariate Cox proportional hazards regression models after adjusting for potentially confounding variables., Results: During the 12-year follow-up period, type 2 diabetes developed in 1437 subjects (16.6%, 1437/8655), with incidence rate of 2.8-5.0 (over 2 years). Compared to the reference first quartile, the HRs (95% CIs) of incident type 2 diabetes in the second, third, and fourth quartiles increased in a dose-response manner after adjusting for potentially confounding variables., Conclusions: High TG/HDL-C ratio at baseline may be a useful surrogate indicator of future incident type 2 diabetes., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Electronegative low-density lipoprotein (LDL) (LDL(-)), a modified LDL that is present in blood and exerts atherogenic effects on endothelial cells and monocytes. This study aimed to determine the action of LDL(-) on monocytes differentiated into macrophages. LDL(-) and in vitro-modified LDLs (oxidized, aggregated, and acetylated) were added to macrophages derived from THP1 monocytes over-expressing CD14 (THP1-CD14). Then, cytokine release, cell differentiation, lipid accumulation, and gene expression were measured by ELISA, flow cytometry, thin-layer chromatography, and real-time PCR, respectively. LDL(-) induced more cytokine release in THP1-CD14 macrophages than other modified LDLs. LDL(-) also promoted morphological changes ascribed to differentiated macrophages. The addition of high-density lipoprotein (HDL) and anti-TLR4 counteracted these effects. LDL(-) was highly internalized by macrophages, and it was the major inductor of intracellular lipid accumulation in triglyceride-enriched lipid droplets. In contrast to inflammation, the addition of anti-TLR4 had no effect on lipid accumulation, thus suggesting an uptake pathway alternative to TLR4. In this regard, LDL(-) upregulated the expression of the scavenger receptors CD36 and LOX-1, as well as several genes involved in triglyceride (TG) accumulation. The importance and novelty of the current study is that LDL(-), a physiologically modified LDL, exerted atherogenic effects in macrophages by promoting differentiation, inflammation, and triglyceride-enriched lipid droplets formation in THP1-CD14 macrophages, probably through different receptors.

Postprandial hypertriglyceridemia is an independent risk factor for cardiovascular disease. The aim of this study was to assess the effects of a single fat-rich meal on barrier functions and inflammatory status on human umbilical vascular endothelial cells (HUVECs), furthermore we assess the effects of mixture of palmitic acid and 25-hydroxycholesterol (PA +25OHCH) on integrity of endothelial cells and their inflammatory properties. HUVECs were induced with serum of healthy volunteers taken before, and 3 h after, the consumption of a meal with a standardized daily required dose of fats. In addition, endothelial cells were induced with PA +25OHCH (800 μM/L+10 μg/mL). Total cholesterol, triglycerides (TGs), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, high sensitivity c-reactive protein, and glucose were measured at fasting and postprandially. HUVEC integrity was measured in the RTCA-DP xCELLigence system. mRNA expression of interleukin (IL)-33, IL-32, intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1), CX3C-chemokine, vascular endothelial growth factor (VEGF) occludin, and VE-cadherin was analyzed by real-time polymerase chain reaction. Viability and apoptosis were assessed in flow cytometry. The level of VEGF and IL-33 in fasting and postprandial serum was assessed by enzyme-linked immunosorbent assay (ELISA). Three hours after consumption of a fatty meal, all patients displayed increased levels of TGs and Toll-like receptors (110 ± 37 mg/dL versus 182 ± 64 mg/dL P  < 0.05) (24 ± 11 mg/dL versus 42 ± 14 mg/dL P  < 0.05). Postprandial serum and PA +25OHCH caused >20% decrease of HUVEC integrity than fasting serum ( P  < 0.001). HUVEC disintegration was accompanied by a decrease of occludin mRNA expression as compared with fasting serum ( P  < 0.05). The fatty meal affected neither VE-cadherin mRNA expression nor its apoptosis ( P  > 0.05). Mixture of PA +25OHCH caused decrease of VE-cadherin mRNA expression as compared with fasting serum ( P  < 0.01). PA +25OHCH did not affect HUVEC apoptosis ( P  > 0.05). Postprandial serum and PA +25OHCH caused increase of IL-33, MCP-1, ICAM-1, IL-32, VEGF, and CX3C-chemokine mRNA expression as compared with fasting serum ( P  < 0.05). Moreover, level of VEGF in fatty serum was significantly higher ( P  < 0.001). Postprandial lipemia after a single fatty meal may destabilize the endothelial barrier and initiate inflammatory processes.

Chylothorax occurs in 2.8-5% of infants after cardiac surgery and can increase morbidity and mortality. First-line conservative treatment consists of a chest tube drainage and a fat-free and medium-chain triglyceride (MCT)-enriched diet. This typically leads to a discontinuity of breast milk feeding due to high content of long-chain triglycerides within the breast milk. Modified breast milk with low fat content (LFBM) could provide numerous benefits like immunological properties of breast milk even for patients with chylothorax. This study was conducted at Herzzentrum Leipzig comparing clinical and growth outcomes between infants with chylothorax after surgery for congenital heart disease treated with LFBM (n = 13) versus MCT-Formula (n = 10). LFBM was prepared by centrifugation of native breast milk added with MCT-oil and fortifier. There were no differences in volume and duration of chest tube drainage between LFBM and MCT-formula treatment groups. Furthermore, no statistically significant differences with regard to weight and length gains could be observed between both feeding groups. LFBM is an efficient and unharmful treatment for chylothorax following cardiac surgery in young children.

Low carbohydrate diets (LC diets) have been noted for adverse health effects. In addition, the effect of lipid composition on an LC diet is unclear. In this study, we used an LC diet containing two different lipids, lard (LC group) and medium-chain triglyceride oil (MCT-LC group), to examine the effect of an LC diet in non-obese mice. Male C57BL/6J mice were fed the control diet or one of the experimental diets ad libitum for 13 weeks. Increased renal weight and glomerular hypertrophy, as well as enlargement of intraglomerular small vessels with wall thickening, were seen in the LC and MCT-LC groups. Renal AMP-activated protein kinase activity was significantly decreased only in the LC diet group. On the other hand, epididymal adipose tissue weight and adipocyte area were markedly decreased only in the MCT-LC group. A positive effect was also observed in the kidney, where different advanced glycation end products, Nε-(carboxyethyl)-lysine and Nε-(carboxymethyl)-lysine, were inhibited depending on the lipid composition of the LC diet. Our findings suggest that, in non-obese conditions, low dietary intake of carbohydrates had both positive and negative impacts. The safety of diets low in carbohydrates, including the effects of fatty acid composition, requires further investigation.

Purpose of Review: Residual risk for atherosclerotic cardiovascular disease (ASCVD) persists even among patients with optimal low-density lipoprotein cholesterol (LDL-C) levels. Randomized trials attempting to modulate other lipids beyond LDL-C have failed to demonstrate significant reductions in ischemic events., Recent Findings: Mounting evidence suggests that triglyceride elevation is an independent risk factor for ASCVD. Though trials of triglyceride-lowering therapy in the statin era have failed to provide protection from ASCVD events, subgroup analyses have revealed that those with the highest triglycerides at time of enrollment appeared to receive the greatest clinical benefit. REDUCE-IT was a trial that enrolled patients with high triglycerides despite having goal LDL-C levels on statin therapy. Treatment with icosapent ethyl, a highly purified omega-3 fatty acid (OM3FA), eicosapentaenoic acid ethyl ester, provided a 25% relative risk reduction for the primary composite cardiovascular endpoint (hazard ratio 0.75, 95% CI 0.68--0.83; P = 0.00000001), as well as a 30% relative risk reduction in total ischemic events (P = 0.00000000036)., Summary: Icosapent ethyl was rigorously shown to decrease residual risk for cardiovascular events, though the benefits seen were likely because of mechanisms beyond mere triglyceride lowering. Clinical application of icosapent ethyl in this cohort of patients with residual risk is urgently needed.

Background & Aims: We performed a meta-analysis of data from recent studies to evaluate the safety and efficacy of parenteral nutrition (PN) with structured triglyceride (STG) lipid emulsions compared to medium-chain triglyceride (MCT)/long-chain triglyceride (LCT) lipid emulsions in Chinese patients., Methods: PubMed, Embase, Cochrane Library, China National Knowledge Internet, Wanfang, and VIP were searched for randomized controlled trials comparing STGs with MCTs/LCTs published in English or Chinese between January 1987 and October 2017. Two independent investigators screened and selected studies according to prespecified selection criteria. Data were pooled and analysed using RevMan ® version 5.3., Results: Thirty-two studies comprising 1944 patients were included in the meta-analysis. Compared with MCT/LCT emulsions, STGs resulted in a shorter hospital length of stay (LOS) (weighted mean difference [WMD], -1.65 days; 95% confidence interval [CI]: -2.63, -0.67; P = 0.001) and lower adverse event rates (relative risk, 0.64; 95% CI: 0.48, 0.85; P = 0.002). STGs were associated with a significantly better cumulative nitrogen balance (WMD, 4.04 g/24 h; 95% CI: 3.10, 4.97; P < 0.0001) as well as higher concentrations of pre-albumin (WMD 35.20 mg/L; 95% CI: 26.59, 43.81; P < 0.0001) and albumin (WMD, 1.64 g/L; 95% CI: 1.17, 2.10; P < 0.0001) compared with MCTs/LCTs. In contrast, significantly lower concentrations of plasma triglycerides (WMD, -0.21 mmol/L; 95% CI: -0.30, -0.12; P < 0.0001), total cholesterol (WMD, -0.45 mmol/L; 95% CI: -0.60, -0.29; P < 0.0001), alanine aminotransferase (WMD, -7.68 IU/L; 95% CI: -9.68, -5.68; P < 0.0001) and aspartate aminotransferase (WMD, -10.27 IU/L; 95% CI: -16.05, -4.49; P = 0.0005) were observed in patients receiving STGs compared with MCT/LCTs. STGs were also associated with reduced inflammation and improved immunological function, as reflected by significantly lower C-reactive protein concentrations (WMD, -2.67 mg/L; 95% CI: -4.55, -0.79; P = 0.005) and increased concentrations of IgG (WMD, 2.11 g/L; 95% CI: 0.23, 3.99; P = 0.03), IgA (WMD, 0.21 g/L; 95% CI: 0.14, 0.28; P < 0.0001), CD3+ (WMD, 5.81%; 95% CI: 0.92, 10.70; P = 0.02), and CD4+/CD8+ (WMD, 0.12; 95% CI: 0.00, 0.24; P = 0.04) compared with MCT/LCTs., Conclusions: Administration of STGs was shown to improve hepatic function, nutrition status, and immunological function and reduce inflammation, LOS, and adverse events compared with MCT/LCTs in Chinese patients receiving PN., (Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Aims: To evaluate the clinical accuracy of novel indices visceral adiposity index (VAI) and body adiposity index (BAI) to identify patients with impaired fasting glucose (IFG) and compare with its individual components and other obesity indicators., Methods: A cross-sectional study was conducted in Mexican population. Body mass index (BMI), waist circumference, hip circumference, triglycerides (TG), High density lipoprotein cholesterol (HDL-C), VAI, BAI, waist to hip ratio (WHR) and waist to height ratio (WHtR) were determined. We plotted a receiver operating characteristic curves to assess the abilities to discriminate subjects with IFG from those with normal glucose tolerance (NGT) of the measurements. A binary logistic regression analysis was performed to determine the strength of association with IFG., Results: A total of 280 individuals were included, from which 144 (51.3%) have IFG; the mean age was 47.14 years and 164 (55.5%) were females. Compared with NGT subjects, the participants with IFG had significantly higher levels of BMI, WHtR, VAI, BAI and TG. The measurements with highest area under the curve were TG, (0.631, 95% confidence interval [CI] 0.566-0.697) VAI (0.628, 95% CI 0.563-0.693) and WHtR (0.622, 95% CI 0.557-0.688) and in the adjusted binary logistic regression model, were found to be independently associated with IFG, Odds Ratio of 2.665, (95% CI 1.567-4.533) 2.567 (95% CI 1.527-4.317) and 2.171 (95% CI 1.102-4.276) respectively., Conclusions: Our data provide evidence that TG, VAI and WHtR could be considered potential tools for the risk assessment of type 2 diabetes mellitus (T2DM) in this population., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: This double-blind, randomised, placebo-controlled, two-part study assessed the impact of GSK2981710, a medium-chain triglyceride (MCT) that liberates ketone bodies, on cognitive function, safety, and tolerability in healthy older adults., Methods: Part 1 was a four-period dose-selection study (n = 8 complete). Part 2 was a two-period crossover study (n = 80 complete) assessing the acute (Day 1) and prolonged (Day 15) effects of GSK2981710 on cognition and memory-related neuronal activity. Safety and tolerability of MCT supplementation were monitored in both parts of the study., Results: The most common adverse event was diarrhoea (100% and 75% of participants in Parts 1 and 2, respectively). Most adverse events were mild to moderate, and 11% participants were withdrawn due to one or more adverse events. Although GSK2981710 (30 g/day) resulted in increased peak plasma β-hydroxybutyrate (BHB) concentrations, no significant improvements in cognitive function or memory-related neuronal activity were observed., Conclusion: Over a duration of 14 days, increasing plasma BHB levels with daily administration of GSK2981710 had no effects on neuronal activity or cognitive function. This result indicates that modulating plasma ketone levels with GSK2981710 may be ineffective in improving cognitive function in healthy older adults, or the lack of observed effect could be related to several factors including study population, plasma BHB concentrations, MCT composition, or treatment duration., (© 2019 John Wiley & Sons, Ltd.)

Purpose of Review: Treatment of hypercholesterolemia with statins results in significant reductions in cardiovascular risk; however, individuals with well-controlled low-density lipoprotein cholesterol (LDL-C) levels, but persistent high triglycerides (TG), remain at increased risk. Genetic and epidemiologic studies have shown that elevated fasting TG levels are associated with incident cardiovascular events. At effective doses, omega-3 fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), lower TG levels but may have additional atheroprotective properties compared to other TG-lowering therapies such as niacin and fibrates. The purpose of this review is to evaluate mechanisms related to the potential benefits of omega-3 fatty acids in atherothrombotic disease., Recent Findings: Large randomized clinical trials are currently under way to test the cardiovascular benefits of omega-3 fatty acids at a pharmacologic dosage (4 g/day). A large randomized trial with a prescription EPA-only formulation was shown to reduce a composite of cardiovascular events by 25% in statin-treated patients with established cardiovascular disease or diabetes and other CV risk factors. EPA and DHA have distinct tissue distributions as well as disparate effects on membrane structure and lipid dynamics, rates of lipid oxidation, and signal transduction pathways. Compared to other TG-lowering therapies, EPA has been found to inhibit cholesterol crystal formation, inflammation, and oxidative modification of atherogenic lipoprotein particles. The anti-inflammatory and endothelial benefits of EPA are enhanced in combination with a statin. Omega-3 fatty acids like EPA only at a pharmacologic dose reduce fasting TG and interfere with mechanisms of atherosclerosis that results in reduced cardiovascular events. Additional mechanistic trials will provide further insights into their role in reducing cardiovascular risk in subjects with well-managed LDL-C but elevated TG levels.

Background: Children with long-chain fatty acid β-oxidation disorders (LCFAOD) presenting with clinical symptoms are treated with a specialist infant formula, with medium chain triglyceride (MCT) mainly replacing long chain triglyceride (LCT). It is essential that the safety and efficacy of any new specialist formula designed for LCFAOD be tested in infants and children., Methods: In an open-label, 21-day, phase I trial, we studied the safety of a new MCT-based formula (feed 1) in six well-controlled children (three male), aged 7-13 years (median 9 years) with LCFAOD (very long chain acyl CoA dehydrogenase deficiency [VLCADD], n=2; long chain 3-hydroxyacyl CoA dehydrogenase deficiency [LCHADD], n=2; carnitine acyl carnitine translocase deficiency [CACTD], n=2). Feed 1 (Lipistart; Vitaflo) contained 30% energy from MCT, 7.5% LCT and 3% linoleic acid and it was compared with a conventional MCT feed (Monogen; Nutricia) (feed 2) containing 17% energy from MCT, 3% LCT and 1.1% linoleic acid. Subjects consumed feed 2 for 7 days then feed 1 for 7 days and finally resumed feed 2 for 7 days. Vital signs, blood biochemistry, ECG, weight, height, food/feed intake and symptoms were monitored., Results: Five subjects completed the study. Their median daily volume of both feeds was 720 mL (range 500-1900 mL/day). Feed 1 was associated with minimal changes in tolerance, free fatty acids (FFA), acylcarnitines, 3-hydroxybutyrate (3-HB), creatine kinase (CK), blood glucose, liver enzymes and no change in an electrocardiogram (ECG). No child complained of muscle pain or symptoms associated with LCFAOD on either feed., Conclusions: This is the first safety trial reported of an MCT formula specifically designed for infants and children with LCFAOD. In this short-term study, it appeared safe and well tolerated in this challenging group.

Aims: We hypothesized that height-corrected abdominal size (supine sagittal abdominal diameter/height ratio [SADHtR] or waist circumference/height ratio [WHtR]) would associate more strongly than body mass index (BMI, weight/height 2 ) with levels of fasting insulin, triglycerides, and three derived biomarkers of insulin resistance., Methods: Anthropometry, including SAD by caliper, was collected on 4398 adults in the 2011-2014 National Health and Nutrition Examination Survey. For comparison purposes, each adiposity indicator was scaled to its population-based, sex-specific, interquartile range (IQR). For each biomarker we created four outcome groups based on equal-sized populations with ascending values. Multivariable polytomous logistic regression modeled the relationships between the adiposity indicators and each biomarker., Results: Highest-group insulin was associated with a one-IQR increment of BMI (RR 4.3 [95% CI 3.9-4.9]), but more strongly with a one-IQR increment of SADHtR (RR 5.7 [5.0-6.6]). For highest-group HOMA-IR the RR for BMI (4.2 [3.7-4.6]) was less than that of SADHtR (6.0 [5.1-7.0]). Similarly, RRs for BMI were smaller than those for SADHtR applying to highest-group triglycerides (RR 1.6 vs 2.1), triglycerides/HDL-cholesterol (RR 1.9 vs 2.4) and TyG index (RR 1.7 vs 2.2) (all p < .001). The RRs for WHtR were consistently between those for SADHtR and BMI. The top 25% of insulin resistance among US adults was estimated to lie above adiposity thresholds of 0.140 for SADHtR, 0.606 for WHtR, or 29.6 kg/m 2 for BMI., Conclusions: Relative abdominal size rather than relative weight may better define adiposity associated with homeostatic insulin resistance. These population-based, cross-sectional findings could improve anthropometric prediction of cardiometabolic risk., (Published by Elsevier B.V.)

The authors hypothesize that consumption of interesterified fats may be the cause of the continuous increase in cardiovascular deaths in the United States which began in 2011. Interesterification is a method of producing solid fats from vegetable oil and began to supplant partial hydrogenation for this purpose upon recognition of the danger of trans fats to cardiovascular health. Long, straight carbon chains, as are present in saturated and trans fatty acids, decrease the fluidity of the erythrocyte cell membrane, which decreases erythrocyte deformability and increases blood viscosity. This decrease in cell membrane fluidity is caused by increased van der Waals interactions, which also solidify dietary fats. Elevated blood viscosity is favored as the pathogenic mechanism by which trans fats increase cardiovascular mortality because changes in lipoprotein levels do not account for all the mortality attributable to their consumption. The rapid changes in cardiovascular mortality noted with the introduction and withdrawal of trans fats from the food supply are reviewed. The evidence implicating elevated blood viscosity in cardiovascular disease is also reviewed. Data regarding the production and consumption of interesterified fats in the US should be released in order to determine if there is an association with the observed increase in cardiovascular deaths.

The use of palm oil by the food industry is increasingly criticized, especially in Italy, for its purported negative effects on human health and environment. This paper summarizes the conclusions of a Symposium on this topic, gathered by the Nutrition Foundation of Italy, among experts representing a number of Italian Medical and Nutritional Scientific Societies. Toxicological and environmental issues were not considered. Participants agreed that: no evidence does exist on the specific health effects of palm oil consumption as compared to other saturated fatty acids-rich fats; the stereospecific distribution of saturated fatty acids in the triacylglycerol molecule of palm oil limits their absorption rate and metabolic effects; in agreement with International guidelines, saturated fatty acids intake should be kept <10% of total energy, within a balanced diet; within these limits, no effect of palm oil consumption on human health (and specifically on CVD or cancer risk) can be foreseen.

Aims: Glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors treat type 2 diabetes through incretin-signaling pathways. This study compared the efficacy and safety of the glucagon-like peptide-1 receptor agonist exenatide once-weekly (Miglyol) suspension for autoinjection (QWS-AI) with the dipeptidyl peptidase-4 inhibitor sitagliptin or placebo., Materials and Methods: In this open-label, multicentre study of patients with type 2 diabetes who had suboptimal glycaemic control on metformin monotherapy, 365 patients were randomized to receive exenatide 2.0 mg QWS-AI, sitagliptin 100 mg once daily or oral placebo (3:2:1 ratio). The primary endpoint was change in glycated hemoglobin (HbA1c) from baseline to 28 weeks., Results: At 28 weeks, exenatide QWS-AI significantly reduced HbA1c from baseline compared to sitagliptin (-1.13% vs -0.75% [baseline values, 8.42% and 8.50%, respectively]; P  = .02) and placebo (-0.40% [baseline value, 8.50%]; P = .001). More exenatide QWS-AI-treated patients achieved HbA1c <7.0% than did sitagliptin- or placebo-treated patients (43.1% vs 32.0% and 24.6%; both P  < .05). Exenatide QWS-AI and sitagliptin reduced fasting plasma glucose from baseline to 28 weeks (-21.3 and -11.3 mg/dL) vs placebo (+9.6 mg/dL), with no significant difference between the 2 active treatments. Body weight decreased with both active treatments (-1.12 and -1.19 kg), but not with placebo (+0.15 kg). No improvement in blood pressure was observed in any group. The most common adverse events with exenatide QWS-AI were gastrointestinal events and injection-site reactions., Conclusions: This study demonstrated that exenatide QWS-AI reduced HbA1c more than sitagliptin or placebo and was well tolerated., (© 2017 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Lipemia retinalis is an unusual ocular finding associated with hypertriglyceridemia. We report the case of an infant treated for retinopathy of prematurity who later developed lipemia retinalis, with triglyceride levels of 4736 mg/dl. There was a paradoxical worsening of hypertriglyceridemia with the use of medium chain triglyceride supplement. On discontinuing the supplement, the triglycerides level drastically dropped, and retinal vasculature returned to a normal hue., (Copyright © 2017 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

We investigated the increasing amounts of medium-chain triacylglycerol (MCT) in the diet on hepatic lipid metabolism. Mature C57BL/6 male mice were randomly divided into five groups (n = 10/group). The animals received their diet for 12 weeks, as a control (C group, 10% of energy from lipids); high-fat lard (HF group, isoenergetic diet, 50% of energy from lipids with lard); a mixture of lard and MCT oil (with a gradual replacement of lard by MCT: HF-MCT25%, HF-MCT75%, and HF-MCT100% groups). At euthanasia, we collected blood and dissected the liver for analyses (glucose, insulin, HOMA-IR, QUICK index, and triacylglycerol, light microscopy, western blotting, and RT-qPCR). The HF diet groups showed a greater body mass gain compared to the C group, but the HF-MCT100% group showed diminished adiposity and amelioration of insulin resistance. All the HF groups also showed a clear increase in hepatic lipid accumulation, increased lipogenesis and decreased PPAR-alpha expression, although HF-MCT groups showed improved local insulin signaling. Lastly, the HF-MCT100% group had raised markers of beta-oxidation (UCP3 and MCAD) and mitochondrial biogenesis (PGC1-alpha and NRF1). In conclusion, the findings demonstrated that a high amount of MCT (HF-MCT100% group) added to an HF diet reduces the body fat accumulation and insulin resistance. However, the lipid accumulation as well as the lipid metabolism is altered in the liver of animals fed with a very high MCT diet, indicating that higher doses of MCT may be harmful in a long-term.

Background & Aims: Ghrelin, a peptide found in the stomach, increases appetite and fat-free mass while suppressing energy expenditure. Ghrelin requires modification by medium-chain triglycerides (MCTs) to exert its physiological effects. In this study, we investigated ghrelin activation and the resulting physiological changes following MCT administration., Methods: Thirty participants were selected from among inpatients diagnosed with anorexia nervosa (AN). The patients were randomly divided into three groups by the MCT content of their nutritional supplement: (1) 'MCT high' (>6 g/day), (2) 'MCT moderate' (1-6 g/day), and (3) 'MCT low' (<1 g/day). Physical factors such as body weight and composition, as well as levels of nutrition-related serum factors such as acylated (active form) and desacyl (inactive form) ghrelin, leptin, growth hormone, insulin-like growth factor, and neuropeptide Y (NPY) were measured at weeks 0, 2, 4, and 6 of the treatment protocol., Results: Significantly higher ghrelin activation was found in the 'MCT high' than in the 'MCT low' group (P < 0.05). The amount of consumed MCT had a curvilinear relationship with the active ghrelin level (P = 0.00). NPY levels in the 'MCT high' group were significantly more elevated than in the 'MCT low' group (P < 0.05). MCT administration did not significantly affect the remaining factors., Conclusions: This study clearly demonstrated that MCT activates ghrelin and increases NPY, suggesting that nutritional supplementation with MCT may be effective for the treatment of AN patients in an emaciated state., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Studies to explore the relationship between self-reported snoring and dyslipidemia, especially high total cholesterol (TC) and high low-density lipoprotein cholesterol (LDL-C), in the general population are still lacking. Our study was designed to examine whether self-reported snoring is significantly associated with dyslipidemia and ascertain the effects of different snoring intensities on dyslipidemia. There were 10,139 participants in our study. After adjustment for all confounding factors, self-reported snoring (OR = 1.207; p = 0.003), moderate (OR = 1.229; p = 0.015), strong (OR = 1.222; p = 0.033), and very strong (OR = 1.467; p = 0.012) snoring intensity, but not low (OR = 1.110; p = 0.224) snoring intensity, were significantly associated with dyslipidemia among adults with BMI (body mass index) ≥ 25 kg/m². In addition, self-reported snoring was significantly associated with high TC (OR = 1.167; p = 0.048) and high LDL-C (OR = 1.228; p = 0.044), rather than low HDL-C (OR = 1.171; p = 0.057) and high triglyceride (TG) (OR = 1.110; p = 0.141). In conclusion, adults with BMI ≥ 25 kg/m² and who experience snoring, especially moderate, strong, and very strong intensity levels of snoring, should be on the alert regarding the possibility of dyslipidemia, especially high LDL-C and high TC., Competing Interests: The authors declare no conflict of interest.

Long-chain fatty acid oxidation disorders (LC-FAOD) can cause cardiac hypertrophy and cardiomyopathy, often presenting in infancy, typically leading to death or heart transplant despite ongoing treatment. Previous data on triheptanoin treatment of cardiomyopathy in LC-FAOD suggested a clinical benefit on heart function during acute failure. An additional series of LC-FAOD patients with critical emergencies associated with cardiomyopathy was treated with triheptanoin under emergency treatment or compassionate use protocols. Case reports from 10 patients (8 infants) with moderate or severe cardiomyopathy associated with LC-FAOD are summarized. The majority of these patients were detected by newborn screening, with follow up confirmatory testing, including mutation analysis; all patients were managed with standard treatment, including medium chain triglyceride (MCT) oil. While on this regimen, they presented with acute heart failure requiring hospitalization and cardiac support (ventilation, ECMO, vasopressors) and, in some cases, resuscitation. The patients discontinued MCT oil and began treatment with triheptanoin, an investigational drug. Triheptanoin is expected to provide anaplerotic metabolites, to replace deficient TCA cycle intermediates and improve effective energy metabolism. Cardiac function was measured by echocardiography and ejection fraction (EF) was assessed. EF was moderately to severely impaired prior to triheptanoin treatment, ranging from 12-45%. Improvements in EF began between 2 and 21days following initiation of triheptanoin, and peaked at 33-71%, with 9 of 10 patients achieving EF in the normal range. Continued treatment was associated with longer-term stabilization of clinical signs of cardiomyopathy. The most common adverse event observed was gastrointestinal distress. Of the 10 patients, 7 have continued on treatment, 1 elected to discontinue due to tolerability issues, and 2 patients died from other causes. Two of the case histories illustrate that cardiomyopathy may also develop later in childhood and/or persist into adulthood. Overall, the presented cases suggest a therapeutic effect of triheptanoin in the management of acute cardiomyopathy associated with LC-FAOD., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Interesterified fats are currently being used to replace trans fatty acids. However, their impact on biological pathways involved in the atherosclerosis development was not investigated. Weaning male LDLr-KO mice were fed for 16weeks on a high-fat diet (40% energy as fat) containing polyunsaturated (PUFA), TRANS, palmitic (PALM), palmitic interesterified (PALM INTER), stearic (STEAR) or stearic interesterified (STEAR INTER). Plasma lipids, lipoprotein profile, arterial lesion area, macrophage infiltration, collagen content and inflammatory response modulation were determined. Macrophage cholesterol efflux and the arterial expression of cholesterol uptake and efflux receptors were also performed. The interesterification process did not alter plasma lipid concentrations. Although PALM INTER did not increase plasma cholesterol concentration as much as TRANS, the cholesterol enrichment in the LDL particle was similar in both groups. Moreover, PALM INTER induced the highest IL-1β, MCP-1 and IL-6 secretion from peritoneal macrophages as compared to others. This inflammatory response elicited by PALM INTER was confirmed in arterial wall, as compared to PALM. These deleterious effects of PALM INTER culminate in higher atherosclerotic lesion, macrophage infiltration and collagen content than PALM, STEAR, STEAR INTER and PUFA. These events can partially be attributed to a macrophage cholesterol accumulation, promoted by apoAI and HDL2-mediated cholesterol efflux impairment and increased Olr-1 and decreased Abca1 and Nr1h3 expressions in the arterial wall. Interesterified fats containing palmitic acid induce atherosclerosis development by promoting cholesterol accumulation in LDL particles and macrophagic cells, activating the inflammatory process in LDLr-KO mice., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Chylothorax occurs in ~3%-5% of infants undergoing cardiac surgery. Standard treatment requires discontinuation of breast milk feeding, due to the abundance of long-chain triglycerides and transition to a medium-chain triglyceride (MCT)-based formula., Objective: To determine the effectiveness of fat-modified breast milk (MBM) for the treatment of chylothorax compared with MCT formula., Materials and Methods: Infants diagnosed with chylothorax following surgery for congenital heart disease between January 2008 and December 2009 at The Hospital for Sick Children were eligible for this nonrandomized open-label study. Treatment infants (n = 8) received mother's own milk that had been modified by removing the fat layer via centrifugation and adding MCT, nutrients, and essential fatty acids to provide an estimated 74 kcal/100 mL and 1.4 g/100 mL protein (MBM group). Control infants (n = 8) received an MCT formula (MCT group). The feeding intervention was a minimum of 6 weeks after chest tube removal per The Hospital for Sick Children standard chylothorax treatment protocol., Results: Daily volume and duration of chest tube drainage were not different between the MBM and MCT groups. While there was no statistically significant difference in rates of weight gain (g/d) between feeding groups, infants in the MBM group, who tended to be younger, experienced a decline in mean weight (P = .04) and length (P = .01) for age z scores., Conclusion: Fat-modified breast milk resolved chylothorax; however, strategies to address poor growth need to be developed and evaluated in larger trials prior to widespread clinical adoption of this novel treatment., (© 2015 American Society for Parenteral and Enteral Nutrition.)

Purpose of Review: The adverse cardiovascular health effects of saturated fats have been debated recently since the publication of studies reporting no increase in cardiovascular risk with saturated fat intakes. We purport that this may be because of the varied nature of saturated fats, which range in length from 2 to over 20 carbon atoms, and review evidence surrounding the cardiovascular health effects of medium-chain triglycerides (MCT)., Recent Findings: MCTs are saturated fats of shorter chain length than other, more readily consumed saturated fats. Studies have reported that consumption of MCT may lead to improvements in body composition without adversely affecting cardio-metabolic risk factors. There may also be synergistic actions between MCT and n-3 polyunsaturated fats that may lead to improvements in cardiovascular health., Summary: It is clinically relevant to distinguish between sources of saturated fats for cardiovascular health. Medium, and possibly shorter chain, saturated fats behave differently than long-chain saturated fats and should not be judged similarly when it comes to their cardio-metabolic health effects. Given their neutral, and potentially beneficial cardiovascular health effects, they should not be categorized together.

Purpose: To evaluate the efficacy and safety profile of carbomer-based lipid-containing artificial tear formulations (CBLAT) in patients with dry eye syndrome., Methods: A multicenter parallel-group study was conducted in 412 patients with dry eye syndrome. Of these patients, 221 switched from using artificial tears to CBLAT (switching group) and 191 added CBLAT to their current treatment (add-on group). Ocular symptom scores, ocular staining grades, tear film breakup time (tBUT), Schirmer I test value, and Korean dry eye level (as defined by the Korean Corneal Disease Study Group guidelines) were evaluated at baseline and after 4 weeks of treatment., Results: After 4 weeks of treatment, ocular surface staining grade, tBUT, Schirmer I value, ocular irritation symptom scores, and the positive rate of visual symptom improved significantly in both groups. Mean reductions in ocular surface staining grades (-0.8 ± 0.9) and ocular irritation symptom scores (-0.8 ± 0.8) in the add-on group were significantly higher than those (-0.5 ± 0.8 and -0.6 ± 0.8) in the switching group (P < 0.01 and P < 0.05). The positive rate of visual symptoms (44.2%) in the add-on group was significantly higher than that (26.4%) in the switching group (P < 0.01). The decrease of Korean dry eye level was 30.1% in the switching group and 51.6% in the add-on group. More patients in the add-on group had decreased dry eye levels than those in the switching group (P < 0.0001)., Conclusions: CBLAT improves ocular surface staining grades, tBUT, Schirmer I values, and ocular symptoms in patients with dry eye syndrome.

Objectives: This is the first clinical trial of this type in Japan, designed to analyze two important aspects of Alzheimer's disease (AD) management using medium-chain triglycerides. Axona was administered for 3 months (40 g of powder containing 20 g of caprylic triglycerides). We used an indurating, four-step dose-titration method (from 10 to 40 g per day) for 7 days before the trial, and examined the tolerance and adverse effects of this intervention. We also investigated its effect on cognitive function in mild-to-moderate AD patients., Patients and Methods: This was a clinical intervention in 22 Japanese patients with sporadic AD at a mild-to-moderate stage (ten females, 12 males), mean age (± standard deviation) 63.9 (±8.5) years, Mini-Mental State Examination (MMSE) score, 10-25, seven patients were ApoE4-positive. During Axona administration, we examined changes in cognitive function by obtaining MMSE and AD assessment-scale scores. Intolerance and serum ketone concentrations were also examined., Results: The tolerance of Axona was good, without severe gastrointestinal adverse effects. Axona did not improve cognitive function in our sample of AD patients, even in those patients without the ApoE4 allele. However, some ApoE4-negative patients with baseline MMSE score ≥14 showed improvement in their cognitive functions., Conclusion: The modified dose-titration method, starting with a low dose of Axona, decreased gastrointestinal adverse effects in Japanese patients. Axona might be effective for some relatively mildly affected patients with AD (with cognitive function MMSE score of ≥14 and lacking the ApoE4 allele).

Lyotropic non-lamellar liquid crystalline (LLC) aqueous nanodispersions hold a great promise in drug solubilization and delivery, but these nanosystems often induce severe hemolysis and complement activation, which limit their applications for safe intravenous administration. Here, we engineer and characterize LLC aqueous nanodispersions from a binary lipid mixture consisting of 2,3-dihydroxypropyl oleate (glyceryl monooleate) and medium-chain triglycerides with tunable internal nanostructures and improved hemocompatibility controlled by citrem as stabilizer. Citrem, in a concentration-dependent manner, modulates the internal nanostructure of LLC dispersions from a biphasic H2/L2 feature to a neat L2 phase, where the latter resembles "thread-like" swollen micelles. Citrem stabilization totally overcomes hemolysis and complement activation, thus realizing the potential of the engineered LLC aqueous nanodispersions for exploitation in intravenous delivery of drugs and contrast agents., From the Clinical Editor: The complement system often gets activated after intravenous injection of nano drug-carriers. This may result in detrimental systemic effects. The authors described in this article the use of citrem as a stabilizing agent and showed the ability of this agent to abolish complement activation. Hence, citrem may prove to be an important component of tunable LLC nanocarriers that may be useful in future clinical setting., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Hypertriglyceridemia has been associated with adverse outcomes in patients receiving intravenous fat emulsions (IVFEs), but little is known about its prevalence and causes., Materials and Methods: The study investigated whether a relationship exists between body mass index (BMI) and triglyceride tolerance in parenterally fed patients. We conducted a retrospective analysis of 287 adults receiving parenteral nutrition to determine whether patients with very low BMI (VLBMI, <16 kg/m(2)) tolerate IVFEs better than do patients with low BMI (LBMI, 16-18.4 kg/m(2)), normal-weight patients (NBMI, 18.5-24.9 kg/m(2)), and overweight/obese patients (HBMI, ≥25 kg/m(2))., Results: The median triglyceride concentration during IVFE was significantly lower in VLBMI patients at 107 mg/dL compared with 124 mg/dL in non-VLBMI patients (P = .016), despite higher lipid infusion rates in the VLBMI group. There was a significant association between triglycerides and BMI in the aggregate cohort (R = 0.2375, P < .0001), with the highest frequency of hypertriglyceridemia occurring in HBMI patients despite relatively lower lipid and energy supply. In a subset of VLBMI patients (n = 36) who had an abdominal computed tomography scan, there was 25- to 100-fold variability in the size of the abdominal adipose tissue depots. In this subgroup, triglyceride concentrations correlated with visceral fat but not subcutaneous abdominal fat., Conclusions: In summary, patients with VLBMI have lower triglyceride concentrations during IVFEs than do other individuals, but there is considerable variability in triglycerides and body fat in this group. Caution should be employed with the use of IVFEs, especially in HBMI patients., (© 2014 American Society for Parenteral and Enteral Nutrition.)

The rise in the prevalence of obesity and metabolic syndrome turned NAFLD as the most common cause of chronic liver diseases worldwide. Although the role of toll like receptors, especially TLR4, as activators of inflammatory pathways in liver diseases is well established, our goal was to investigate if TLR4 activation could modulate metabolic lipid pathways and alter the onset of NAFLD. We used LDL receptor-deficient mice (LDLrKO) fed with an atherogenic diet as a model. The role of TLR4 activation was evaluated by crossing LDLrKO mice with the TLR4 knockout mice. Animals were fed for 12weeks with high-fat high-cholesterol diet (HFD) containing 18% saturated fat and 1.25% cholesterol. TLR4/LDLr KO mice presented lower triacylglyceride (TAG) plasma levels when compared to LDLrKO, despite the type of diet ingested. HFD induced TAG and cholesterol accumulation in the liver of all mice genotypes studied, but TLR4/LDLr KO presented lower TAG accumulation than LDLrKO mice. Gene expression of TAG synthesis enzymes (ApoB100, MTTP, GPAT1 and GPAT4) was not differentially altered in TLR4/LDLr KO and LDLrKO mice. On the other hand, TLR4 deficiency enhanced the expression of several enzymes involved in the oxidation of fatty acids, as follows: ACOX, CPT-1, MTPa, MTBb, PBE and 3-ketoacyl-CoA thiolase. Acyl-carnitine plasma profile showed an increase in C0 and C2 concentration in TLR4/LDLr KO group, corroborating the hypothesis of increased fat oxidation. Our results indicate that TLR4 may have an important role in the onset of steatosis, once its depletion enhances fatty acid oxidation in the liver of mice, preventing triglyceride accumulation., (Copyright © 2015 Elsevier B.V. All rights reserved.)

n-3 Long-chain PUFA up-regulate intestinal lipid metabolism. However, whether these metabolic effects of PUFA on intestine are mediated by AMP-activated protein kinase (AMPK) remains to be elucidated. To determine the effects of α-linolenic acid (ALA) on intestinal fatty acid (FA) metabolism and whether these effects were affected by AMPK deletion, mice deficient in the catalytic subunit of AMPKα1 or AMPKα2 and wild-type (WT) mice were fed either a high-fat diet (HF) or HF supplemented with ALA (HF-A). The results showed that ALA supplementation decreased serum TAG content in WT mice. ALA also increased mRNA expression of genes (carnitine palmitoyltransferase 1a, acyl-CoA oxidase 1, medium-chain acyl-CoA dehydrogenase, cytochrome P450 4A10 and pyruvate dehydrogenase kinase isoenzyme 4a) involved in intestinal lipid oxidation and mRNA expression of TAG synthesis-related genes (monoacylglycerol O-acyltransferase 2, diacylglycerol O-acyltransferases 1 and 2) in WT mice. Consistent with these, expression levels of phosphorylated AMPKα1 and AMPKα2 were also increased in WT mice after ALA addition. However, in the absence of either AMPKα1 or AMPKα2, ALA supplementation failed to increase intestinal lipid oxidation. In addition, no significant effects of either diet (HF and HF-A) or genotype (WT, AMPKα1(-/-) and AMPKα2(-/-)) on FA uptake in the intestine and faecal TAG output were observed. Our results suggest that AMPK is indispensable for the effects of ALA on intestinal lipid oxidation.

A 74-year-old man presented with a subacute severe thoracic polyradiculopathy affecting the T4-T8 dermatomes bilaterally. Extensive investigation demonstrated markedly raised triglyceride levels of 44 mmol/L (<1.7). The patient's unique presentation is discussed alongside a review of triglyceride-induced neurotoxicity and therapeutic management., (2015 BMJ Publishing Group Ltd.)

The question of whether heated fats in the diet may be detrimental to health is nowadays of the upmost concern, but finding an answer is not easy and requires careful consideration of different aspects of lipid oxidation. This review is divided into two sections. The first part deals with the nature of the new compounds formed at high temperature in the frying process as well as their occurrence in the diet while the second part focuses on their possible nutritional and physiological effects. Oxidation products present in abused frying fats and oils are the compounds most suspected of impairing the nutritional properties of the oils or involving adverse physiological effects. The recent studies on their health implications include those related to their fate and those focused on their effects in metabolic pathways and the most prevalent diseases.

Objective: The present study discusses paclitaxel (PTX)-loaded mannosylated-DSPE (Distearoyl-phosphatidyl-ethanolamine) solid lipid nanoparticles (M-SLNs) using mannose as a lectin receptor ligand conjugate for lung cancer targeting and to increase the anticancer activity of PTX against A549 lung's epithelial cancer cells., Materials and Methods: The PTX-SLNs were prepared by solvent injection method and mannose was conjugated to the free amine group of stearylamine. The M-SLNs obtained were characterized for their particle size, polydispersity index, zeta potential and morphology by transmission electron microscope., Results: The M-SLNs were spherical in shape with 254 ± 2.3 nm average size, positive zeta potential (3.27 mV), 79.4 ± 1.6 drug entrapment efficiency and showed the lower extent of drug release 40% over 48 h in vitro. Cytotoxicity study on A549 cell lines and biodistrubtion study of drug revealed that M-SLNs deliver a higher concentration of PTX as compared to PTX-SLNs in an alveolar cell site., Discussion and Conclusion: These results suggested that mannosylated M-SLNs are safe and potential vector for lung cancer targeting.