Medium-chain Fatty Acids Research Articles

Improvement of myocardial lipolysis in iodine-123-beta-methyl-P-iodophenyl-pentadecanoic acid scintigraphy in patients with idiopathic triglyceride deposit cardiomyovasculopathy treated with Tricaprin

Abstract Background Triglyceride deposit cardiomyovasculopathy (TGCV) is a rare intractable cardiovascular disorder (Orphanet ORPHAcode: 565612) in which defective intracellular lipolysis results in heart failure and coronary artery disease. Myocardial scintigraphy with iodine-123-β-methyl-P-iodophenyl-pentadecanoic acid (BMIPP) is useful for evaluating myocardial TG metabolism and its washout rate (WR) reflects myocardial lipolysis. A decreased WR (<10%) of BMIPP is one of the diagnostic criteria for TGCV. CNT-01, the active ingredient of which is tricaprin, a medium-chain triglyceride, has the potential to facilitate myocardial lipolysis in a mouse model. However, the effects of CNT-01 (tricaprin) on BMIPP scintigraphy in patients with TGCV remain unclear. Purpose To evaluate the effects of CNT-01 on BMIPP-WR in patients with TGCV. Methods An investigator-initiated, randomized, double-blind exploratory trial (Phase IIa) was conducted. Ten patients with idiopathic TGCV in our hospital were enrolled and orally administered 1.5 g/day of CNT-01 or placebo for 8 weeks. The endpoint was the delta WR on BMIPP scintigraphy. All the participants underwent BMIPP scintigraphy after overnight fasting. Following the protocol recommended by the Japanese Society of Nuclear Cardiology, 111 MBq of BMIPP was intravenously injected at rest after fasting for ≥ 12 h. Early and delayed images were obtained after 20 and 180–210 min, respectively. BMIPP scintigraphy at baseline and 8-week was performed using the same SPECT apparatus. WR is defined as the ratio of the difference between the counts in the early image and time-decay-corrected delayed image divided by the former. We used a recently proposed algorithm for calculating the WR based on the total count and analyzed the WRs (Ann Nucl Cardiol. 2023;9(1):19-25). Results A total of 5 patients were assigned to placebo and 5 patients were assigned to CNT-01. During the protocol, delta BMIPP-WRs were -6.18 ± 4.43 and 5.44 ± 2.57 % (95% confidence intervals, -12.33 to -0.03 and 1.88 to 9.00) in the placebo and CNT-01 groups, respectively. The baseline-adjusted difference in delta BMIPP-WR between the two groups was significant (p=0.005) (Picture). No significant changes were observed in clinical parameters. Conclusion This study demonstrated that CNT-01 improved myocardial lipolysis in patients with TGCV as measured by BMIPP scintigraphy.

Effects of Krill Oil and Coconut Oil on Inflammatory Processes in Rats With Chronic Unpredictable Mild Stress-Induced Depression and Obesity Model.

This study was conducted to determine the effects of two different types of fat (krill oil [KO] and coconut oil [CO]) on obesity, behavioral tests, and some inflammatory markers when consumed with a high-fat or control diet in rats with depression. The study was conducted mainly in two phases: the induction of depression (37 days) and the dietary intervention (60 days). After the induction of depression by chronic unpredictable mild stress, dietary intervention started. Sixty male Sprague-Dawley rats were divided into 6 groups with 10 rats in each group: (1) standard diet (SD), (2) SD + 5% KO, (3) SD + 5% medium-chain triglyceride (MCT)* (*CO to contain 5% MCT), (4) high-fat diet (HFD), (5) HFD + 5% KO, and (6) HFD + 5% MCT*. The open field test (OFT), forced swimming test (FST), and sucrose preference test were performed at baseline, end of the depression induction, and dietary intervention to observe behavioral changes in rats. After the final behavioral test, animals were sacrificed, and blood samples were collected for biochemical analyses C-reactive protein (milligram per liter), cortisol (microgram per deciliter), and insulin (micro-international units per milliliter) to assess inflammatory changes in the blood. All data were analyzed under two headings: baseline, end of depression induction, end of dietary intervention, and dietary intervention groups. Body weight gain was highest in the SD+KO and lowest in the SD+MCT group (P < .05). When behavioral tests were evaluated according to dietary intervention, it was found that the SD+MCT group spent the most time in the center, the least time in the periphery, and the lowest immobilization time (P < .05). In FST, the SD+KO with the highest weight gain was the most immobile group (P < .05). The study indicates that the weight-reducing effects of MCTs resulted in positive behavioral responses, particularly in OFT and FST. Through these properties, MCTs can be used medicinally in the prevention and treatment of behavioral changes due to depression.

Metabolic Effects of Medium-Chain Triacylglycerol Consumption are Preserved in Obesity.

Several health beneficial effects are associated with intake of medium-chain triacylglycerol (MCT), however, the underlying mechanisms are unknown. Furthermore, it remains uncertain whether the acute metabolic effects of MCT differ between lean individuals and individuals with obesity - and whether these effects are sustained following chronic intake. This study aimed to elucidate the postprandial physiological and metabolic effects of MCT before and after eight days intake compared to intake of energy-matched triacylglycerol consisting of long-chain fatty acids (LCT) using a randomized cross-over design in lean individuals (n=8) and individuals with obesity (n=8). The study revealed that consumption of MCT increased ketogenesis and metabolic rate, while lowering blood glucose levels over five hours. The hypoglycemic action of MCT intake was accompanied by a concomitant transient increase in plasma insulin and glucagon levels. Interestingly, the effects on ketogenesis, metabolic rate, and glycemia were preserved in individuals with obesity and sustained after eight days of daily supplementation. Lipidomic plasma analysis in lean individuals (n=4) showed that a part of the ingested MCT bypasses the liver and entered the systemic circulation as medium-chain fatty acids (MCFA). The findings suggest that MCFA, along with ketone bodies from the liver, may act as signaling molecules and/or substrates in the peripheral tissues, thereby contributing to the effects of MCT intake. In summary, these findings underscore the health benefits of MCT in metabolically compromised individuals after daily supplementation. Moreover, we uncover novel aspects of MCFA biology, providing insights into how these fatty acids orchestrate physiological effects in humans.

The synergistic effect of α-tocopherol and phloretin-loaded nanoemulsions on improvement of the stability, antioxidant, and tyrosinase inhibitory potentiality.

The purpose of this study was to prepare and evaluate the formulation of nanoemulsions (NEs) to encapsulate phloretin (PT) to improve its stability, antioxidant, and tyrosinase inhibitory competence. The aim of this study was to improve the stability, antioxidant, and tyrosinase inhibitory effects of PT via NEs. The formulations were prepared using low energy emulsification method for PT-VE-NEs, α-tocopherol (Vitamin E) and medium chain triglycerides (MCT) were used as the oil phase, and Tween 60 was used as the emulsifier and PEG-400 as the co-emulsifier. The droplet size and zeta potential of oil-in-water NEs were evaluated using dynamic light scattering. The PT-VE-NEs were also characterized by transmission electron microscopy and Fourier transform infrared spectroscopy. The mean droplet diameter was 14.85±0.14nm, with a zeta potential of -2.47±0.51mV. Fourier transform infrared spectroscopy revealed the formation of molecular interactions in the NEs formulations. PT-VE-NEs size was maintained the same during the in vitro digestion study. The particle size of PT-VE-NE remained stable during in vitro digestion. The addition of VE significantly improved the antioxidant, tyrosinase inhibitory effects, as well as thelion and physical stability of PT-VE-NE. The results revealed that NEs is a promising strategy to improve the functionality and stability of PT and VE. PT-VE-NEs will be applied for the preservation of fruits.

Ultrasonic Fabrication of Catechin Nanoemulsions from Green Tea with Enhanced Stability and Antioxidant Activity Optimized by Box-Behnken Design

Nanoemulsions are emulsions, either O/W (oil in water) or W/O (water in oil), with droplet diameters typically ranging from 50 to 1,000 nm. Research indicates that nanoemulsions are highly effective in enhancing the bioavailability, bioactivity, digestibility, stability, safety, quality and sensory attributes of food components. The study aimed to determine the optimum formulation and ultrasonic condition for fabricating catechin nanoemulsion (Ca-NE) from green tea with improved physical stability and antioxidant activity using response surface methodology. The effects of Medium Chain Triglyceride oil concentration (7.5 - 12.5 % w/w), Tween® 80 concentration (1 - 5 % w/w) and sonication time (5 - 15 min) on the droplet size, polydispersity index (PDI) and antioxidant activity presented by DPPH value of the Ca-NE were investigated using Box-Behnken design (BBD). The results found that droplet size and antioxidant activity of the Ca-NE were significantly (p &lt; 0.05) affected by the proposed parameters, whereas the PDI value was slightly affected by those factors. The BBD results suggested that the Ca-NE fabrication condition was optimized with 7.5 % (w/w) oil concentration, 5 % (w/w) Tween® 80 concentration and a sonication time of 10.87 min. The optimum nanoemulsion showed good physical stability in terms of droplet size and PDI and had higher antioxidant activity than unencapsulated catechins when stored at 4 and 30 °C for 90 days. This study showed that catechin nanoemulsions fabricated by ultrasonication had good stability and antioxidant activity and, hence, had high potential for food and beverage applications in the food industry. HIGHLIGHTS The optimum nanoemulsion had good physical stability regarding droplet size and PDI when stored at 4 and 30 °C for 90 days. The ultrasonic fabrication of Ca-NE results in better retention of antioxidant activity than unencapsulated catechins. The ultrasonic fabrication provided the Ca-NE with good stability and high antioxidant activity. The results suggest that the obtained nanoemulsion of catechins has great potential in food or pharmaceutical applications. GRAPHICAL ABSTRACT

Grouper bone nano-calcium and substitution long-chain triglyceride (LCT) into medium-chain triglyceride (MCT) enhanced calcium bioavailability and rat’s bone density

BACKGROUND: The most effective strategy to prevent osteopenia or osteoporosis in the old life is to consume an adequate amount of calcium from childhood through adulthood. OBJECTIVE: This study compared the bioavailability of CaCO3 which is the standard non-dairy calcium supplementation with grouper bone nano-calcium (GBN) combined with various percentages of Long-Chain Triglyceride (LCT) into Medium-Chain Triglyceride (MCT) on calcium bioavailability and rat’s bones density. METHODS: This study was carried out during the rat’s growth period, from the weaning until the rats reached 16 weeks. Thirty-five weaned rats were separated into seven groups and fed varied feeds for 12 weeks. The seven groups of feed were (1) CCa: standard feed AIN-93G, (2) C0: standard calcium deficient feed (without calcium), (3) G0: GBN + MCT:LCT 0 : 100%, (4) G25: GBN + MCT:LCT 25 : 75%, (5) G50: GBN + MCT:LCT 50 : 50%, (6) G75: GBN + MCT:LCT 75 : 25%, and (7) G100: GBN + MCT:LCT 100 : 0%. Parameters observed were serum levels of calcium, phosphorus, and alkaline phosphatase, femur bone characteristics, bone microarchitecture by histomorphometry, micro computed-tomography (μCT), and mechanical strength. RESULTS: The CCa and G100 groups had the best dietary results based on all parameters. The G100 group was superior to CCa in calcium and phosphorus bioavailability, rat’s bone strength and density. CONCLUSIONS: G100: GBN + MCT:LCT 100 : 0% group feed beneficially affected the bioavailability of calcium, was letting he rat’s bones to develop properly, had high density, and been strong throughout the growth phase.

Exclusive enteral nutrition initiates individual protective microbiome changes to induce remission in pediatric Crohn's disease.

Exclusive enteral nutrition (EEN) is a first-line therapy for pediatric Crohn's disease (CD), but protective mechanisms remain unknown. We established a prospective pediatric cohort to characterize the function of fecal microbiota and metabolite changes of treatment-naive CD patients in response to EEN (German Clinical Trials DRKS00013306). Integrated multi-omics analysis identified network clusters from individually variable microbiome profiles, with Lachnospiraceae and medium-chain fatty acids as protective features. Bioorthogonal non-canonical amino acid tagging selectively identified bacterial species in response to medium-chain fatty acids. Metagenomic analysis identified high strain-level dynamics in response to EEN. Functional changes in diet-exposed fecal microbiota were further validated using gut chemostat cultures and microbiota transfer into germ-free Il10-deficient mice. Dietary model conditions induced individual patient-specific strain signatures to prevent or cause inflammatory bowel disease (IBD)-like inflammation in gnotobiotic mice. Hence, we provide evidence that EEN therapy operates through explicit functional changes of temporally and individually variable microbiome profiles.

Oral Administration of a Novel, Synthetic Ketogenic Compound Elevates Blood β-Hydroxybutyrate Levels in Mice in Both Fasted and Fed Conditions.

Elevating ketone levels with therapeutic nutritional ketosis can help to metabolically manage disease processes associated with epilepsy, diabetes, obesity, cancer, and neurodegenerative disease. Nutritional ketosis can be achieved with various dieting strategies such as the classical ketogenic diet, the modified Atkins diet, caloric restriction, periodic fasting, or the consumption of exogenous ketogenic supplements such as medium-chain triglycerides (MCTs). However, these various strategies can be unpleasant and difficult to follow, so that achieving and sustaining nutritional ketosis can be a major challenge. Thus, investigators continue to explore the science and applications of exogenous ketone supplementation as a means to further augment the therapeutic efficacy of this metabolic therapy. Here, we describe a structurally new synthetic triglyceride, glycerol tri-acetoacetate (Gly-3AcAc), that we prepared from glycerol and an acetoacetate precursor that produces hyperketonemia in the therapeutic range (2-3 mM) when administered to mice under both fasting and non-fasting conditions. Animal studies were undertaken to evaluate the potential effects of eliciting a ketogenic response systemically. Acute effects (24 h or less) were determined in male VM/Dk mice in both fasted and unfasted dietary states. Concentration levels of β-hydroxybutyrate in blood were elevated (βHB; 2-3 mM) under both conditions. Levels of glucose were reduced only in the fasted state. No detrimental side effects were observed. Pending further study, this novel compound could potentially add to the repertoire of methods for inducing therapeutic nutritional ketosis.

Ketogenic Approaches for the Treatment of Alzheimer's Disease.

Dementia represents one of the largest and most urgent public health problems across the globe. Modeling projections have estimated that delaying the onset of Alzheimer's disease (AD) by 6 months would reduce the prevalence by 5%, while a delay of 12 months would reduce the prevalence by 10%. One approach to achieving a delay in the onset of AD is to investigate lifestyle interventions that could be widely implemented with a favorable risk-benefit relationship and socioeconomic profile. Amongst such interventions, there is increasing evidence to support the use of ketogenic interventions in AD. Indeed, it is well known that cerebral glucose metabolism is impaired in AD, even at a preclinical stage, and a growing body of literature suggests that these findings may represent a primary pathogenic mechanism leading to neurodegeneration. Ketones are readily taken up by the brain and can serve as an alternative energy source for neurons and glia, hypothetically bypassing the glucose uptake deficit in AD. In this invited review we discuss the preclinical as well as clinical work aiming to increase ketones as a primary intervention in AD, including variations of the ketogenic diet, medium chain triglyceride supplementation, and newer, more experimental approaches.

Antifungal effects of three natural branched medium-chain fatty acids and their potential as fumigants against Aspergillus flavus in stored peanut seeds

The contamination of peanuts with aflatoxins predominantly produced by Aspergillus flavus poses a worldwide threat to both food safety and agricultural economies. Antifungal compounds from natural sources may offer a safe and effective alternative strategy to control A. flavus in peanuts. We evaluated the contact and fumigant antifungal effects of three natural branched medium-chain fatty acids (branched-MCFAs), (E)-2-methyl-2-pentenoic acid, 2-methylhexanoic acid, and 2-methylheptanoic acid against A. flavus relative to their straight-chain isomers and sorbic acid a commonly used preservative. In vitro experiments showed that the inhibitory effects of these three branched-MCFAs on A. flavus were stronger than their straight-chain isomers and sorbic acid. In addition, fumigant effects of the branched-MCFAs were more effective than their direct contact inhibitory effects against the growth of A. flavus. 2-Methylhexanoic acid, 2-methylheptanoic acid, and (E)-2-methyl-2-pentenoic acid showed significant fumigant activity, with the minimum inhibitory concentration (MIC) values of 0.10, 0.10, and 0.12 g/l air, respectively. Fumigation of these branched-MCFAs also significantly slowed the growth of A. flavus in peanut seeds, and completely inhibited A. flavus growth at 2.0 g/l air. After 24 h of fumigation exposure to the branched-MCFAs, the fumigated A. flavus on medium or peanut seeds was re-incubated to observe whether the A. flavus could continue to grow, and the results revealed that the in vitro and in vivo minimum fungicidal concentrations (MFC) were 0.15 and 2.5 g/l air, respectively. This study indicated that these three natural branched-MCFAs have strong antifungal fumigation activity with application potential in protecting peanut seeds from A. flavus contamination during storage.

The clinical characteristics of systemic lupus erythematosus-related thoracic duct obstruction: a retrospective case-control study from China.

To investigate the clinical characteristics and treatment strategies of patients with systemic lupus erythematosus-related thoracic duct obstruction (SLE-TDO). Clinical data, laboratory tests, imaging data, and treatment strategies were retrospectively collected from 428 SLE patients with TDO treated from January 2010 to December 2020 at Beijing Shijitan Hospital. TDO was confirmed by TD imaging examination. We retrospectively examined 20 SLE patients with TDO as the case group, and 80 randomly matched SLE patients without any lymph-vessel dysfunction as the control group. The prevalence of TDO in patients with SLE was 4.67%, and the in-hospital fatality rate was 5%. Of these patients, 50% presented with TDO as the initial manifestation of SLE, with the others first diagnosed with SLE followed by TDO. The average SLE disease activity index (SLEDAI) was 7 ± 3.8. All patients were treated with glucocorticoids (GC) and immunosuppressants combined with a medium-chain triglycerides (MCT) diet. Eleven patients received TD-related surgery in parallel with anti-rheumatic treatment. Polyserositis, anti-Sm antibody positivity, and SLEDAI score were found to be independent risk factors for TDO in patients with SLE. While SLE patients may develop TDO during the course of their disease, TDO can also be the initial presentation of SLE. TDO should therefore attract the attention of rheumatologists and the surgeon. GC and immunosuppressants combined with lymphatic surgery may be an effective therapeutic strategy for SLE-TDO to relieve symptoms and improve prognosis. Key Points • Thoracic duct obstruction (TDO) is a rare complication of SLE. • SLE may develop TDO during the disease course, while TDO can also be the initial presentation of SLE, which should attract the attention of physicians. • Glucocorticoids and immunosuppressants combined with lymphatic surgery may be an effective therapeutic strategy for SLE-TDO to relieve symptoms and to improve prognosis.

Effects of monoglyceride blend on systemic and intestinal immune responses, and gut health of weaned pigs experimentally infected with a pathogenic Escherichia coli

BackgroundMonoglycerides have emerged as a promising alternative to conventional practices due to their biological activities, including antimicrobial properties. However, few studies have assessed the efficacy of monoglyceride blend on weaned pigs and their impacts on performance, immune response, and gut health using a disease challenge model. Therefore, this study aimed to investigate the effects of dietary monoglycerides of short- and medium-chain fatty acids on the immunity and gut health of weaned pigs experimentally infected with an enterotoxigenic Escherichia coli F18.ResultsPigs supplemented with high-dose zinc oxide (ZNO) had greater (P < 0.05) growth performance than other treatments, but no difference was observed in average daily feed intake between ZNO and monoglycerides groups during the post-challenge period. Pigs in ZNO and antibiotic groups had lower (P < 0.05) severity of diarrhea than control, but the severity of diarrhea was not different between antibiotic and monoglycerides groups. Pigs fed with monoglycerides or ZNO had lower (P < 0.05) serum haptoglobin on d 2 or 5 post-inoculation than control. Pigs in ZNO had greater (P < 0.05) goblet cell numbers per villus, villus area and height, and villus height:crypt depth ratio (VH:CD) in duodenum on d 5 post-inoculation than pigs in other treatments. Pigs supplemented with monoglycerides, ZNO, or antibiotics had reduced (P < 0.05) ileal crypt depth compared with control on d 5 post-inoculation, contributing to the increase (P = 0.06) in VH:CD. Consistently, pigs in ZNO expressed the lowest (P < 0.05) TNFa, IL6, IL10, IL12, IL1A, IL1B, and PTGS2 in ileal mucosa on d 5 post-inoculation, and no difference was observed in the expression of those genes between ZNO and monoglycerides. Supplementation of ZNO and antibiotic had significant impacts on metabolic pathways in the serum compared with control, particularly on carbohydrate and amino acid metabolism, while limited impacts on serum metabolites were observed in monoglycerides group when compared with control.ConclusionsThe results suggest that supplementation of monoglyceride blend may enhance disease resistance of weaned pigs by alleviating the severity of diarrhea and mitigating intestinal and systemic inflammation, although the effectiveness may not be comparable to high-dose zinc oxide.

Linseed oil supplementation alters milk fatty acid profile, mitigates heat stress, and improves summer milk yield in grazing dairy cows.

Dietary supplementation of fat can be an important source of energy to compensate for the reduction in dry matter intake in dairy cows during heat stress periods. Studies have reported that supplementing dairy cow diets with linseed oil (LO) can increase milk yield and enhance the levels of beneficial fatty acids, such as omega-3 fatty acids, in the milk. The objective of this research was to evaluate the effect of LO supplementation on milk fatty acids profile, milk yield and composition, and physiological parameters of grazing cows. The study was conducted in two seasons, one in spring and one in summer. A 2 × 2 Latin square design was used in each experiment. Twelve Holstein and crossbred Holstein x Jersey cows were involved in each season. Cows were divided into two groups: control (TC) with no supplementation and treatment (TL) supplemented with 400g/day of LO. The results showed that LO supplementation altered the milk fatty acid profile: decreased concentrations of short and medium-chain fatty acids (C10:0 - C17:1) except for C13:0 and increased concentrations of long-chain fatty acids (C18, C18:1 (both trans and cis isomers), C18:2 (specific conjugated linoleic acid - CLA isomers), and C18:3 n3 (omega-3)). Additionally, milk yield increased by 1.5l per day during summer in LO-supplemented cows, while milk fat, protein, and casein content decreased. Milk stability increased by 2.2% in the LO-supplemented group. LO-supplemented cows reduced internal body temperature and heart frequency in the afternoon and increased daily rumination time by 20min. In conclusion, LO supplementation can be an effective strategy to improve the nutritional profile of milk by altering fatty acid composition towards potentially healthier fats, mitigate the negative effects of heat stress on grazing cows during summer, as evidenced by reduced body temperature and heart frequency and increase milk yield.

Enhancing the fermentation rate and aroma compounds of kiwi wine via the addition of nitrogen during the stationary phase

Nitrogen addition is a viable strategy for preventing sluggish or stuck fermentation and enhancing aroma profiles in the winemaking industry. Herein, nitrogen, in the form of amino acids mixture or diammonium hydrogen phosphate (DAP), was added at different fermentation periods to investigate its effects on the fermentation characteristics, non-volatile compounds and aroma profiles of kiwi wines. Both the amino acids mixture and DAP shortened fermentation time by 1–2 days and balanced organic acid proportion by reducing malic acid content and increasing citric acid content. Adding DAP significantly decreased higher alcohols content, whereas higher alcohols content was remarkably increased with amino acids mixture supplementation. Furthermore, nitrogen addition during the stationary phase was most conducive to synthesizing other beneficial aromas, especially acetate esters and medium-chain fatty acid ethyl esters (MCFAEEs), and improving the perception of tropical fruity and cream aromas in kiwi wines. Partial least-squares regression (PLSR) results showed there was a tight correlation between amino acids and volatile compounds. This study provides an insight into the development of high-quality kiwi wine and should serve as the theoretical foundation to support the application of nitrogen addition in the wine industry.

Beyond Anaerobic Digestion: New Perspectives for the Development of a Biorefinery Platform for the Simultaneous Production of Medium-Chain Fatty Acids by Chain Elongation and Biogas from Food Wastes

Beyond Anaerobic Digestion: New Perspectives for the Development of a Biorefinery Platform for the Simultaneous Production of Medium-Chain Fatty Acids by Chain Elongation and Biogas from Food Wastes

The Enteric Bacterium Enterococcus faecalis Elongates and Incorporates Exogenous Short and Medium Chain Fatty Acids Into Membrane Lipids.

Enterococcus faecalis incorporates and elongates exogeneous short- and medium-chain fatty acids to chains sufficiently long to enter membrane phospholipid synthesis. The acids are activated by the E. faecalis fatty acid kinase (FakAB) system and converted to acyl-ACP species that can enter the fatty acid synthesis cycle to become elongated. Following elongation the acyl chains are incorporated into phospholipid by the PlsY and PlsC acyltranferases. This process has little effect on de novo fatty acid synthesis in the case of short-chain acids, but a greater effect with medium-chain acids. Incorporation of exogenous short-chain fatty acids in E. faecalis was greatly increased by overexpression of either AcpA, the acyl carrier protein of fatty acid synthesis, or the phosphate acyl transferase PlsX. The PlsX of Lactococcus lactis was markedly superior to the E. faecalis PlsX in incorporation of short-chain but not long-chain acids. These manipulations also allowed unsaturated fatty acids of lengths too short for direct transfer to the phospholipid synthesis pathway to be elongated and support growth of E. faecalis unsaturated fatty acid auxotrophic strains. Short- and medium-chain fatty acids can be abundant in the human gastrointestinal tract and their elongation by E. faecalis would conserve energy and carbon by relieving the requirement for total de novo synthesis of phospholipid acyl chains.

Comparison of the Effect of Omega-3 vs. MCT Supplementation on Iron-Related Indices in Patients Undergoing Dialysis.

Chronic kidney disease (CKD), characterized by progressive kidney failure, significantly increases mortality and comorbidity risks such as anemia. This study contrasts the impacts of omega-3 and medium-chain triglycerides (MCT) oil on levels of iron, ferritin, total iron-binding capacity (TIBC), hemoglobin (Hb), and transferrin saturation in patients with CKD undergoing dialysis. This interventional trial was conducted on 120 patients with CKD undergoing dialysis in Rasht, Iran. For 8weeks, the omega-3 group was orally administered three 1000-mg capsules of omega-3 fatty acid supplement, and the MCT group was administered three 1000-mg capsules containing MCT oil daily. Serum concentrations of ferritin, iron, TIBC, Hb, and transferrin saturation were assessed pre-intervention and after the intervention. There was a significant increase in serum iron levels in the MCT group compared to the omega-3 group (103.72 ± 57.8vs. 77.48±40.13; P = 0.031). No effect was found regarding other iron-related factors such as TIBC, Hb, transferrin saturation, and ferritin levels. The results of our study indicated that taking MCT oil increased serum iron levels compared to omega-3 supplementation in patients with CKD undergoing dialysis. Further research is needed to better understand the potential benefits of MCT oils in patients with CKD.

Eicosapentaenoic Acid and Medium-Chain Triacylglycerol Structured Lipid Supplementation Improves Muscular Endurance Exercise Performance and Reduces Muscle Fatigue in Young Healthy Male

Objective Structured lipids containing medium-chain fatty acids, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) from fish oil (EPA/MCT) and it improve overall endurance. However, their effects on local muscle endurance remain unclear. This study aimed to investigate the effects of EPA/MCT intake on muscle endurance during leg extension exercises and subsequent muscle fatigue. Methods This 8-week, placebo-controlled, randomized, double-blind parallel-group trial involved 20 healthy young men. Subjects were randomly assigned to an EPA/MCT group (10 subjects) and a placebo group (PL group, 10 subjects). They consumed 4560 mg of the test food daily for 8 wk before an exercise intervention. The EPA/MCT supplement contained 600 mg of EPA, 260 mg of DHA, and 1890 mg of MCT (1110 mg of octanoic acid and 780 mg of decanoic acid). After the 8-week intervention, the subjects performed four sets of leg extension exercises at 40% of their body weight until exhaustion. The number of repetitions per set and the total repetitions across the four sets served as indicators of muscle endurance. Isometric maximum voluntary contraction (MVC), range of motion, circumference, muscle thickness, echo intensity, and muscle stiffness were measured before and after exercise to assess muscle fatigue. Results There was no difference between the groups in the number of repetitions for sets 1–4 or in the total number of repetitions during the leg extension exercise. In the EPA/MCT group, a significant negative correlation was observed between the increase in the blood EPA/AA ratio and the rate of decrease in the number of repetitions. Additionally, the decrease in MVC after exercise was significantly smaller in the EPA/MCT group than in the PL group. Conclusion Our study results suggest that an 8-week intake of EPA/MCT can increase the blood EPA/AA ratio and improve muscle endurance performance. Additionally, EPA/MCT intake reduces muscle fatigue after exercise.

Triheptanoin in patients with long-chain fatty acid oxidation disorders: clinical experience in Italy

BackgroundLong-chain fatty acid oxidation disorders (LC-FAOD) are rare and potentially life-threatening diseases that cause deficient energy production and accumulation of toxic metabolites. Despite dietary management, adherence to maximum fasting guidelines, restricted long-chain triglyceride intake and supplementation with medium-chain triglyceride (MCT) oil (current standard of care), most patients experience recurrent decompensation episodes that can require hospitalisation. Herein, we analysed the effectiveness and safety of triheptanoin (a highly purified, synthetic medium odd-chain triglyceride) treatment in a cohort of Italian patients with LC-FAOD.MethodsThis retrospective, nationwide study included nine patients with LC-FAOD who switched from standard therapy with MCT oil to triheptanoin oral liquid. Data were collected between 2018 and 2022. Clinical outcome measures were the number and duration of intercurrent catabolic episodes and number and duration of metabolic decompensation episodes requiring hospitalisation. Creatine kinase (CK) levels and treatment-related adverse effects were also reported.ResultsPatients were provided a mean ± standard deviation (SD) triheptanoin dose of 1.5 ± 0.9 g/kg/day in four divided administrations, which accounted for 23.9 ± 8.9% of patients’ total daily caloric intake. Triheptanoin treatment was started between 2.7 and 16 years of age and was continued for 2.2 ± 0.9 years. The number of intercurrent catabolic episodes during triheptanoin treatment was significantly lower than during MCT therapy (4.3 ± 5.3 vs 22.0 ± 22.2; p = 0.034), as were the number of metabolic decompensations requiring hospitalisation (mean ± SD: 2.0 ± 2.5 vs 18.3 ± 17.7; p = 0.014), and annualised hospitalisation rates and duration. Mean CK levels (outside metabolic decompensation episodes) were lower with triheptanoin treatment versus MCT oil for seven patients. No intensive care unit admissions were required during triheptanoin treatment. Epigastric pain and diarrhoea were recorded as adverse effects during both MCT and triheptanoin treatment.ConclusionsThe significant improvement in clinical outcome measures after the administration of triheptanoin highlights that this treatment approach can be more effective than MCT supplementation in patients with LC-FAOD. Triheptanoin was well tolerated and decreased the number of intercurrent catabolic episodes, metabolic decompensation episodes requiring hospitalisation, and the annualised rate and duration of hospitalisations.

12548 Mammary De Novo Lipogenesis During A Hyperinsulinemic-euglycemic Clamp

Abstract Disclosure: T.M. Fordham: None. M. Ramos-Roman: None. E.J. Parks: Consulting Fee; Self; Simply Good Foods. Stock Owner; Self; Sagimet Biosciences. Other; Self; Past President of The Obesity Society. Introduction: The mammary produces large amounts of medium-chain saturated fatty acids. Long-chain saturated fatty acids found in human milk primarily derive from the maternal diet or from the mobilization of stored triglycerides. Previous studies have established the importance of insulin in stimulating mammary differentiation, milk synthesis, and lipogenesis. However, no studies have assessed how changes in insulin concentrations alter human mammary de novo lipogenesis (DNL) nor what effect gestational diabetes may have on insulin’s relationship to lipogenesis during lactation. Through the utilization of stable isotopes and the hyperinsulinemic-euglycemic clamp technique, we tested the differing concentrations of insulin to stimulate mammary DNL. Methods: Eight women (32±4 yrs) with (GDM, n=4) or without (NGT, n=4) recent gestational diabetes and overweight or obesity (28.2±2.9 kg/m2) were recruited to participate in this study at 6 weeks postpartum. The night before the study, participants orally consumed 3 doses of 70% deuterated water to label newly made fatty acids. Participants arrived in the morning for IV placement and immediately pumped milk contralaterally for 20 minutes. Milk was pumped two hours later, again at the end of step 1 of the clamp (10 mU/m2/min) and once more after step 2 (either 20 or 40 mU/m2/min). Milk triglycerides were extracted and prepared for analysis by gas chromatography-mass spectrometry. The incorporation of deuterium into milk triglyceride-fatty acids was the primary outcome. Results: Fasting insulin concentrations were significantly associated with newly-made 16:0 in milk triglycerides (r=0.85, P=0.01). Of all measured triglyceride 16:0, 1.6±1.0% were made de novo. This percentage increased 1.5-fold by the end of step 2 of the clamp (P=0.06). Fasting milk DNL 14:0 was 12.3±4.8% which was significantly greater than DNL 16:0 (P&amp;lt;0.01). DNL 14:0 increased 1.7-fold during step 2 (P=0.04). For both milk triglyceride 12:0 and 14:0 derived from DNL, a significant effect across clamp-stage was observed (P&amp;lt;0.001 for both), but not an effect of group (P=0.12, P=0.11, respectively). Bonferroni posthoc analyses revealed that the insulin effect was significant for both groups for 12:0 (GDM, P=0.02; NGT, P &amp;lt;0.01) and 14:0 (GDM, P&amp;lt;0.01; NGT, P=0.01). Interpretation: The present study is the first to assess the acute effect of a hyperinsulinemic-euglycemic clamp on the synthesis of newly-made triglyceride fatty acids in human milk. These results suggest that the increases in mammary DNL may be fatty acid specific, favoring that of lauric and myristic acids, but not longer chain fatty acids like palmitate. Mammary lipogenesis was stimulated by insulin in all subjects regardless of recent gestational diabetes diagnosis. The role mammary DNL plays in overall milk fat content deserves further investigation. Presentation: 6/3/2024