Plasma Triacylglycerol Concentrations Research Articles

Effects of Amino Acid Supplementation on Liver Lipid Content: A Randomized, Double-Blinded, Placebo-Controlled Trial

Abstract Objectives To test whether chronic ingestion of essential amino acids (EAAs) plus arginine lowers liver lipid content when compared with a placebo (non-essential amino acids; NEAAs). Methods Older adults (50–75 y) with elevated fasting plasma triacylglycerol (TAG) concentrations were recruited into the study. After screening (week -2), all participants ingested placebo (NEAAs; alanine, aspartic acid, and serine) capsules twice daily (between meals) for two weeks and 3 T nuclear magnetic resonance spectroscopy scans were used to determine baseline (week 0) liver lipid percentage. Participants were then randomised to receive capsules containing 11 g of EAAs plus arginine (n = 10) or NEAAs (n = 9) twice daily for eight weeks, using a double-blinded design. Follow-up NMR spectroscopy scans were conducted at eight weeks after the onset of randomised supplementation (week 8) to determine the impact on liver lipids. Results Liver lipid percentage (mean ± standard deviation) was not significantly altered by randomised supplementation in either the EAAs plus arginine group (Pre: 9.08 ± 7.90%; Post: 8.94 ± 6.91%; P = 0.65) or the NEAAs group (Pre: 10.23 ± 7.20%; Post: 9.65 ± 7.70%; P = 0.18). Change in fasting plasma TAG during placebo run-in (Week 0 minus screening) was significantly negatively correlated with change in liver lipid content (week 8 minus week 0) for the EAAs plus arginine group (r = −0.722; P = 0.02), but not for the NEAAs group A (r = −0.479; P = 0.19). Conclusions Eight weeks of essential amino acids plus arginine ingestion did not significantly lower liver lipid content in older adults. However, ingestion of non-essential amino acids during the run-in period may have influenced the effect on liver fat of subsequent randomised amino acid supplementation, suggesting further investigation is warranted. Funding Sources The study was sponsored by NIH/NIA (award to EB), and the Roy and Christine Sturgis Charitable Trust (award to NMH). Screenings and study visits were undertaken within the ITS-Clinical Research Center at UTMB, funded by NIH/NCRR, and within the UAMS Donald W. Reynolds Institute on Aging at UAMS, funded by NIH/NIA. NMH and EB were also funded by the Arkansas Biosciences Institute, the major research component of the Arkansas Tobacco Settlement Proceeds Act of 2000.

No Difference in Lipemic Response or Endothelial Function Following Interesterified and Non-Interesterified Functionally Equivalent Fats: A Randomized Controlled Trial

Abstract Objectives Interesterified (IE) fats are now used as hard fats to replace harmful trans fats, however the cardiometabolic health impact of the most commonly consumed IE fat blends are unknown. The InterCardio study (NCT03438084) investigated the effect of the most commonly consumed IE spread versus functionally equivalent hard fats and a control oil, on postprandial lipemia (PPL) and acutely changing markers of endothelial function. Methods A four-armed, double blind, randomized controlled trial in healthy males and females (n = 50) aged 35–75 years compared sequential test meals (0 h; 897 kcal, 50 g fat, 16 g protein, 88 g carbohydrate, 5 h; 550 kcal, 30 g fat, 15 g protein, 39 g carbohydrate) on postprandial plasma triacylglycerol (TG) concentrations, endothelial function (flow mediated dilation (FMD)), plasma nitrite concentrations and NADPH oxidase activity. Test fats were: a commercially available IE spread, a functionally equivalent non-IE spread, spreadable butter (SB), and a high-MUFA oil (rapeseed oil) as control. Melt curve data for the spreadable fats showed similar solid fat content at 37°C (IE; 0.3%, non-IE; 0.4%, SB; 0%). Blood was collected at fasting and regular intervals up to 8 hrs, and FMD was measured at fasting, 4.5 hrs and 7.5 hrs. Results All 4 test fats increased TG levels postprandially, reaching peak concentrations at 6 hrs. There was no significant treatment or treatment x time effects on plasma TAG concentrations (P = 0.684), nor incremental areas under the curves up to 4 and 8 hrs; mean iAUC0–8 h (95% CI) were 5.4 mmol/L.h (4.3, 6.4) for IE spread, 5.7 mmol/L.h (4.3, 6.8) for non-IE spread, 5.5 mmol/L.h (4.0, 7.0) for SB and 5.9 mmol/L.h (4.3,6.8) for rapeseed oil. There were no significant treatment effects on endothelial function, while nitrite concentrations and NADPH oxidase activity reduced postprandially. Mean NAPDH oxidase activity following IE spread, non-IE spread, SB and rapeseed oil at 6 h were 322, 333, 270, and 268 respectively. Conclusions In the first study to investigate the acute effects of commercially relevant IE and non-IE spreads and SB, we report no adverse effect of IE fats on acutely changing cardiometabolic risk factors relative to a high-MUFA reference oil. The similar effects on endothelial function and postprandial lipemia is likely to be due to their similar solid fat content at body temperature. Funding Sources BBSRC.

Lactation Versus Formula Feeding: Insulin, Glucose, and Fatty Acid Metabolism During the Postpartum Period.

Milk production may involve a transient development of insulin resistance in nonmammary tissues to support redistribution of maternal macronutrients to match the requirements of the lactating mammary gland. In the current study, adipose and liver metabolic responses were measured in the fasting state and during a two-step (10 and 20 mU/m2/min) hyperinsulinemic-euglycemic clamp with stable isotopes, in 6-week postpartum women who were lactating (n = 12) or formula-feeding (n = 6) their infants and who were closely matched for baseline characteristics (e.g., parity, body composition, and intrahepatic lipid). When controlling for the low insulin concentrations of both groups, the lactating women exhibited a fasting rate of endogenous glucose production (EGP) that was 2.6-fold greater and a lipolysis rate that was 2.3-fold greater than the formula-feeding group. During the clamp, the groups exhibited similar suppression rates of EGP and lipolysis. In the lactating women only, higher prolactin concentrations were associated with greater suppression rates of lipolysis and lower intrahepatic lipid and plasma triacylglycerol concentrations. These data suggest that whole-body alterations in glucose transport may be organ specific and facilitate nutrient partitioning during lactation. Recapitulating a shift toward noninsulin-mediated glucose uptake could be an early postpartum strategy to enhance lactation success in women at risk for delayed onset of milk production.

Dietary betaine improves egg-laying rate in hens through hypomethylation and glucocorticoid receptor–mediated activation of hepatic lipogenesis-related genes

In avian species, liver lipid metabolism plays an important role in egg laying performance. Previous studies indicate that betaine supplementation in laying hens improves egg production. However, it remains unclear if betaine improves laying performance by affecting hepatic lipid metabolism and what mechanisms are involved. We fed laying hens a 0.5% betaine-supplemented diet for 4 wks to investigate its effect on hepatic lipids metabolism in vivo and confirmed its mechanism via in vitro experiments using embryonic chicken hepatocytes. Results showed that betaine supplemented diet enhanced laying production by 4.3% compared with normal diet, accompanied with increased liver and plasma triacylglycerol concentrations (P < 0.05) in hens. Simultaneously, key genes involved in hepatic lipid synthesis, such as sterol regulatory element binding protein 1 (SREBP-1), fatty acid synthase, acetyl-CoA carboxylase, and stearoyl-CoA desaturase 1 (SCD1) were markedly upregulated at the mRNA level (P < 0.05). Western blot results showed that SREBP-1 and SCD1 protein levels were also increased (P < 0.05). Moreover, mRNA expression of main apolipoprotein components of yolk-targeted lipoproteins, apolipoprotein B (ApoB) and apolipoprotein-V1 (ApoV1), in addition to microsomal triglyceride transfer proteins, which is closely related to the synthesis and release of very-low density lipoprotein, were also markedly elevated (P < 0.05). Methylated DNA immunoprecipitation combined with PCR detects reduction of methylation levels in certain regions of the above gene promoters. Chromatin immunoprecipitation PCR assays showed increased binding of glucocorticoid receptor (GR) to SREBP1 and ApoB gene promoters. Similar results of ApoV1 gene expression were obtained from cultured hepatocytes treated with betaine. Additionally, betaine increased the expression of GR and some genes involved in methionine cycle in vitro. These results suggest that betaine supplementation could alter the expression of liver lipid synthesis and transport-related genes by modifying the methylation status and GR binding on their promoter and hence promote the synthesis and release of yolk precursor substances in the liver.

Emulsion Droplet Crystallinity Attenuates Postprandial Plasma Triacylglycerol Responses in Healthy Men: A Randomized Double-Blind Crossover Acute Meal Study

The presence of triacylglycerol (TAG) cystallinity is assumed to influence digestibility and postprandial lipemia (PPL), although studies to date are limited. This study aimed to investigate whether the presence of solid fat compared with undercooled liquid oil, specifically, plays a role in determining PPL by comparing emulsion droplets differing only in terms of physical state. Ten percent palm stearin and 0.4% sorbitan monostearate emulsions were tempered to contain identically sized, charged, and shaped (spherical) undercooled liquid (LE) compared with partially crystalline solid (SE; mean±SEM: 33.2%±0.03% solid fat at 37°C) droplets. Fifteen healthy fasting adult men (mean±SD age: 27.5±5.7 y; BMI: 24.1±2.5 kg/m2) consumed 500 mL of each emulsion on separate occasions and plasma TAG concentrations, particle size of the plasma chylomicron-rich fraction (CMRF), and fatty acid (FA) composition of the CMRF-TAG were serially determined in a 6-h postprandial randomized double-blind crossover acute meal study. Changes from baseline values were analyzed by repeated-measures ANOVA. An earlier (2 compared with 3 h, P<0.05) significant rise, a 39.9% higher mean postprandial TAG change from baseline (P=0.08), and higher peak concentration (mean±SEM: 1.47±0.19 compared with 1.20±0.15 mmol/L, P=0.04) and iAUC (1.95±0.39 compared with 1.45±0.31 mmol/L×h, P=0.03) values were observed for LE compared with SE. The compositions of the CMRF-TAG FAs shifted toward those of the ingested palm stearin by 4 h but did not differ between SE and LE (P=0.90). Nor were there differences in postprandial changes in CMRF particle size (P=0.79) or nonesterified FAs (P=0.72) based on lipid physical state. Despite their identical compositions and colloidal properties, differences in lipid absorption were observed between SE and LE in healthy adult men. This is direct evidence that TAG physical state contributes to PPL, with the presence of solid fat having an attenuating influence.This trial was registered at clinicaltrials.gov as NCT03515590.

Interesterification of a commonly consumed palm-based hard fat blend does not affect postprandial lipoprotein metabolism in healthy older adults

AbstractInteresterified (IE) fats are widely used to replace partially-hydrogenated fats as hard fats with functional and sensory properties needed for spreads/margarines, baked goods, and confectionary, while avoiding the health hazards of trans fats. Detailed mechanistic work to determine the metabolic effects of interesterification of commonly-consumed hard fats has not yet been done. Earlier studies using fats less commonly consumed have shown either neutral or a lowering effect on postprandial lipaemia. We investigated postprandial lipaemia, lipoprotein remodelling, and triacylglycerol-rich lipoprotein (TRL) fraction apolipoprotein concentrations following a common IE blend of palm oil/kernel fractions versus its non-IE counterpart, alongside a reference monounsaturated (MUFA) oil. A 3-armed, double blind, randomized controlled trial (clinicaltrials.gov NCT03191513) in healthy adults (n = 20; 10 men, 10 women) aged 45–75 y, assessed effects of single meals (897 kcal, 50 g fat, 16 g protein, 88 g carbohydrate) on postprandial plasma triacylglycerol (TAG) concentrations, lipoprotein profiles, and TRL fraction apolipoprotein B48 and TAG concentrations. Test fats were IE 80:20 palm stearin/palm kernel fat, the equivalent non-IE fat, and a high-MUFA reference oil (rapeseed oil, RO). Blood was collected at baseline and hourly for 8 h. Linear mixed modelling was performed, adjusting for treatment order and baseline values (ver. 24.0; SPSS Inc., Chicago, IL, USA). Total 8 h incremental area under the curves (iAUC) for plasma TAG concentrations were lower following IE and non-IE compared with RO (mean difference in iAUC: non-IE vs. RO -1.8 mmol/L.h (95% CI -3.3, -0.2); IE vs. RO -2.6 mmol/L.h (95% CI -5.3, 0.0)), but iAUCs for IE and non-IE were not significantly different. There were no differences between IE and non-IE for chylomicron fraction apoB48 concentrations nor TAG:apoB48 ratio. No differences were observed between IE and non-IE for lipoprotein (VLDL, HDL, LDL) particle size or sub-class particle concentrations. However, LDL particle diameters were reduced at 5 and 6 h following IE vs RO (P &lt; 0.05). XXL- (including chylomicron remnants and VLDL particles), XL- and L-VLDL particle concentrations (average diameters &gt; 75, 64, and 53.6 nm respectively) were higher following IE and non-IE vs. RO at 6 h (P &lt; 0.05) and 8 h postprandially (P &lt; 0.005–0.05). In conclusion, both IE and non-IE palmitic acid-rich fats generated a greater preponderance of pro-atherogenic large TRL remnant particles in the late postprandial phase relative to an oleic acid-rich oil. However, the process of interesterification did not modify postprandial TAG response or lipoprotein metabolism.

Short Sprints Accumulated at School Modulate Postprandial Metabolism in Boys.

This study examined the efficacy of maximal sprint running accumulated during a typical school day to modulate postprandial metabolism in adolescent boys. Nineteen adolescent boys completed three 2-d experimental conditions: a standard-practice control (CON), an accumulated in-school sprint running (ACC), and a single block of afterschool sprint running (BLO). On day 1, a fasting capillary blood sample was taken at 0735 h in the school. Three subsequent postprandial blood samples were taken at predetermined times after consumption of standardized breakfast and lunch. During ACC, participants accumulated four sets of 10 × 30-m maximal-intensity sprint runs across natural breaks in lessons. During BLO, participants performed the same number of sprints (40) in a single after-school exercise session. The blood samples from day 1 were replicated on the day after exercise (day 2). On day 1, no significant differences in total area under the plasma triacylglycerol concentration versus time curve (TAUC-TAG) were observed between conditions (P = 0.126). However, TAUC-insulin was lower in ACC compared with BLO (-26%, effect size [ES] = 0.86, P = 0.001) and CON (-22%, ES = 0.72, P = 0.010). On day 2, TAUC-TAG was 12% lower after ACC (ES = 0.49; P = 0.002) and 10% lower after BLO (ES = 0.37; P = 0.019) compared with CON. No significant differences were observed between conditions on day 2 for postprandial insulin or glucose (P ≥ 0.738). Four sets of 10 × 30-m sprints, accumulated in four separate bouts (<5 min) during the school day, reduced postprandial triacylglycerol and insulin concentrations in adolescent boys and may represent an effective in-school exercise strategy to promote metabolic health.

Relationship between semen quality and seminal plasma cholesterol, triacylglycerols and proteins in the domestic cat.

The current study aimed to evaluate the relationship between specific seminal plasma components - cholesterol (CHOL), triacylglycerols (TAG) and total protein (PROT) concentrations - and semen quality in cats. A further aim was to determine the relationship between specific seminal protein bands and semen quality. Thirteen toms, 2-5 years of age, were included. Semen collection was performed by electroejaculation every 4 weeks. Fifty-eight ejaculates were assessed for motility, velocity, volume, sperm concentration, total sperm count, viability, acrosome integrity, plasma membrane integrity and sperm morphology. Samples were divided into two groups: good semen quality (GSQ) and poor semen quality (PSQ). After evaluation, seminal plasma was separated from the sperm by centrifugation and stored at -20°C. CHOL, TAG and PROT concentrations were then assessed and seminal plasma protein profile was determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Seminal plasma CHOL and TAG concentrations, motility, velocity, sperm concentration, total sperm count and sperm morphology were significantly higher in GSQ cats compared with PSQ cats (P <0.01). Moreover, seminal plasma SDS-PAGE analysis showed an identifiable extra band exclusively in the GSQ group. Data obtained in this study showed that seminal plasma CHOL and TAG concentrations and specific protein bands could be used to improve semen evaluation in toms. In this sense, the 14 kDa protein band could be a valuable marker for semen quality in the cat and should be further investigated. However, more studies are necessary to determine its relationship with fertility.

Effects of rumen-protected choline on the inflammatory and metabolic status and health of dairy cows during the transition period

The objectives of this study were to evaluate the effects of rumen-protected choline (RPC) supplementation from 21 d pre- to 21 d postpartum on markers of metabolic status and inflammatory response, concentrations of liposoluble vitamins, and plasma total Ca in parous Holstein cows. The hypotheses were that supplementing RPC during the transition period would reduce hepatic triacylglycerol accumulation postpartum and attenuate markers of inflammatory response following parturition, and collectively, such responses were expected to benefit health of dairy cows. Parous cows at 241 d of gestation were blocked by parity group and 305-d milk yield, and within block, they were assigned randomly to receive either 0 g/d [no choline in transition (NT), n = 55] or 12.9 g/d choline ion [choline in transition (CT), n = 58] from 21 d pre- to 21 postpartum. The RPC product was individually top-dressed onto the total mixed ration once daily. Prepartum, treatments were supplemented (mean ± standard deviation) for the last 18.8 ± 5.7 and 19.2 ± 5.0 d of gestation in NT and CT, respectively. Supplementing RPC prepartum did not affect concentrations of plasma metabolites and inflammatory markers during the last 3 wk of gestation. Postpartum, cows fed RPC had greater hepatic concentration of hepatic triacylglycerol (NT = 3.4 vs. CT = 4.4%) and tended to have increased concentration of β-hydroxybutyrate (NT = 0.48 vs. CT = 0.53 mM) in plasma. In spite of the increased hepatic triacylglycerol in cows fed RPC, treatment did not affect the concentrations of the inflammatory marker tumor necrosis factor-α or of the positive acute phase proteins, haptoglobin and fibrinogen. Supplementing choline tended to increase the concentration of plasma triacylglycerol by 0.69 mg/dL in the first 21 d postpartum and reduced the incidence of subclinical hypocalcemia by 20.9 percentage units compared with NT. Supplementing transition cows with RPC did not affect the concentrations of liposoluble vitamins in the first 7 d postpartum or the incidence of individual diseases or morbidity in early lactation. The inability of supplemental choline to reduce hepatic triacylglycerol might have been a consequence of the increased productive performance without additional dry matter intake.

Effect of mountain ultra-marathon running on plasma angiopoietin-like protein 4 and lipid profile in healthy trained men

PurposeAngiopoietin-like protein 4 (ANGPTL4) regulates lipid metabolism by inhibiting lipoprotein lipase activity and stimulating lipolysis in adipose tissue. The aim of this study was to find out whether the mountain ultra-marathon running influences plasma ANGPTL4 and whether it is related to plasma lipid changes.MethodsTen healthy men (age 31 ± 1.1 years) completed a 100-km ultra-marathon running. Plasma ANGPTL4, free fatty acids (FFA), triacylglycerols (TG), glycerol (Gly), total cholesterol (TC), low (LDL-C) and high (HDL-C) density lipoprotein-cholesterol were determined before, immediately after the run and after 90 min of recovery.ResultsPlasma ANGPTL4 increased during exercise from 68.0 ± 16.5 to 101.2 ± 18.1 ng/ml (p < 0.001). This was accompanied by significant increases in plasma FFA, Gly, HDL-C and decreases in plasma TG concentrations (p < 0.01). After 90 min of recovery, plasma ANGPTL4 and TG did not differ significantly from the exercise values, while plasma FFA, Gly, TC and HDL-C were significantly lower than immediately after the run.TC/HDL-C and TG/HDL-C molar ratios were significantly reduced. The exercise-induced changes in plasma ANGPTL4 correlated positively with those of FFA (r = 0.73; p < 0.02), and HDL-C (r = 0.69; p < 0.05). Positive correlation was found also between plasma ANGPTL4 and FFA concentrations after 90 min of recovery (r = 0.77; p < 0.01).ConclusionsThe present data suggest that increase in plasma FFA during mountain ultra-marathon run may be involved in plasma ANGPTL4 release and that increase in ANGPTL4 secretion may be a compensatory mechanism against fatty acid-induced oxidative stress. Increase in plasma HDL-C observed immediately after the run may be due to the protective effect of ANGPTL4 on HDL.

Dietary Supplementation of 25-Hydroxycholecalciferol Improves Livability in Broiler Breeder Hens-Amelioration of Cardiac Pathogenesis and Hepatopathology.

Simple SummaryBroiler breeder hens with higher bodyweights (BW) and fat accumulation suffered sudden death earlier in conjunction with compromised heart rhythms and over-ventilation. Pathological cardiac hypertrophy and functional failure are causative factors of sudden death with exacerbation by hepatopathology. Dietary 25-OH-D3 supplementation improved hen’s livability and heart health by ameliorating systemic hypoxia, acidosis, and cardiac pathological hypertrophy through calcineurin-NFAT4c signaling and MHC-β expression in association with reduced hepatic steatosis and fibrosis.A supplement of 69 μg 25-hydroxycholecalciferol (25-OH-D3)/kg feed increased livability in feed restricted (R-hens) broiler breeder hens by 9.9% and by 65.6% in hens allowed ad libitum feed intake (Ad-hens) in a feeding trial from age 26–60 weeks. Hens with higher bodyweight and/or adiposity suffered sudden death (SD) earlier in conjunction with compromised heart rhythms and over-ventilation. In the study with the same flock of hens, we demonstrate that 25-OH-D3 improved hen’s livability and heart health by ameliorating systemic hypoxia, acidosis, and cardiac pathological hypertrophy through calcineurin-NFAT4c signaling and MHC-β expression in association with reduced plasma triacylglycerol and hepatic steatosis and fibrosis (p < 0.05). In contrast to live hens sampled at 29, 35, and 47 weeks, SD hens exhibited severe cardiac hypertrophy that was either progressive (Ad-groups) or stable (R-groups). Actual and relative liver weights in SD hens from any group declined as the study progressed. Heart weight correlated significantly to total and relative liver weights in SD-hens of both R- and Ad-groups. In contrast to normal counterparts sampled at 35 and 47 weeks, R-hens exhibiting cardiac hypertrophy experienced severe hypoxia and acidosis, with increased bodyweight, absolute and relative weights of liver and heart, hepatic and plasma triacylglycerol content, and cardiac arrhythmia (p < 0.05). The present results demonstrate that pathological cardiac hypertrophy and functional failure are causative factors of SD and this pathogenic progression is accelerated by hepatopathology, particularly during the early age. Increased feed efficiency with rapid gains in BW and fat increase hens’ risk for hypoxia, irreversible cardiac hypertrophy, and arrhythmias that cause functional compromise and SD. Additional supplementation of 69 mg/kg feed of 25-OH-D3 to the basal diet is effective to ameliorate cardiac pathogenesis and prevent SD in broiler breeder hens.

Oral administration of α-ketoglutarate enhances nitric oxide synthesis by endothelial cells and whole-body insulin sensitivity in diet-induced obese rats.

Obesity is a risk factor for many chronic diseases, including hypertension, type-2 diabetes, and cancer. Interestingly, concentrations of branched-chain amino acids (BCAAs) in plasma are commonly associated with endothelial dysfunction in humans and animals with obesity. Because L-leucine inhibits nitric oxide synthesis by endothelial cells (EC), we hypothesized that dietary supplementation with AKG (a substrate for BCAA transaminase) may stimulate BCAA catabolism in the small intestine and extra-intestinal tissues, thereby reducing the circulating concentrations of BCAAs and increasing nitric oxide synthesis by endothelial cells. Beginning at four weeks of age, male Sprague-Dawley rats were fed a low-fat or a high-fat diet for 15 weeks. At 19 weeks of age, lean or obese rats continued to be fed for 12 weeks their respective diets and received drinking water containing 0 or 1% AKG ( n = 8/group). At 31 weeks of age, the rats were euthanized to obtain tissues. Food intake did not differ ( P &gt; 0.05) between rats supplemented with or without AKG. Oral administration of AKG (250 mg/kg BW per day) reduced ( P &lt; 0.05) concentrations of BCAAs, glucose, ammonia, and triacylglycerols in plasma, adiposity, and glutamine:fructose-6-phosphate transaminase activity in endothelial cells, and enhanced ( P &lt; 0.05) concentrations of the reduced form of glutathione in tissues, nitric oxide synthesis by endothelial cells, and whole-body insulin sensitivity (indicated by oral glucose tolerance test) in both low-fat and high-fat rats. AKG administration reduced ( P &lt; 0.05) white adipose tissue weights of rats in the low-fat and high-fat groups. These novel results indicate that AKG can reduce adiposity and increase nitric oxide production by endothelial cells in diet-induced obese rats. Impact statement Obesity is associated with elevated concentrations of branched-chain amino acids, including L-leucine. L-Leucine inhibits the synthesis of nitric oxide from L-arginine by endothelial cells, contributing to impairments in angiogenesis, blood flow, and vascular dysfunction, as well as insulin resistance. Reduction in the circulating levels of branched-chain amino acids through dietary supplementation with α-ketoglutarate to promote their transamination in the small intestine and other tissues can restore nitric oxide synthesis in the vasculature and reduce the weights of white adipose tissues, thereby improving metabolic profiles and whole-body insulin sensitivity (indicated by oral glucose tolerance test) in diet-induced obese rats. Our findings provide a simple and effective nutritional means to alleviate metabolic syndrome in obese subjects. This is highly significant to combat the current obesity epidemic and associated health problems in humans worldwide.

Effect of Acute Ingestion of Green Tea Extract and Lemon Juice on Oxidative Stress and Lipid Profile in Pigs Fed a High-Fat Diet.

Green tea and its catechins have been shown to ameliorate high fat diet-induced oxidative stress and hyperlipidemia. However, low bioavailability of catechins limits their therapeutic potential. Lemon juice (LJ) has been suggested to enhance the bioavailability of catechins in vitro. This study investigated the antioxidative and hypolipidemic efficacy of a single dose of green tea extract (GTE) or GTE plus LJ (GTE + LJ) in high-fat diet fed pigs. Sixteen pigs ingested a single dose of GTE (190 mg/kg/day) or GTE + LJ (0.75 mL/kg/day) mixed with low-fat (LF; 5% fat) or high-fat (HF; 22% fat) diets and blood samples were collected for 24 h. Plasma catechin level peaked at two hours, and gradually returned to baseline after six hours following the intake. The addition of LJ significantly increased plasma catechin level. The diet containing GTE did not lower plasma cholesterol and triacylglycerol (TG) concentrations, superoxide dismutase (SOD) and catalase activity, or malondialdehyde concentration in 24 h in HF-fed pigs. Addition of a single dose of LJ, however, significantly decreased plasma TG level in LF groups but did not cause further changes on any other markers compared to the GTE alone. Our findings indicate limited effect of a single meal containing GTE on plasma antioxidant enzymes, lipid profile, and lipid peroxidation in pigs and no significant synergistic/additive action of adding LJ to GTE within 24 h in pigs. A study with a longer treatment period is warranted to further understand the potential role of GTE in reducing HF diet-induced oxidative stress and the possible synergistic role of LJ.

Effects of abomasal infusions of fatty acids and one-carbon donors on hepatic ceramide and phosphatidylcholine in lactating Holstein dairy cows

Our objectives were to (1) determine whether the abomasal infusion of behenic acid (C22:0) elevated hepatic ceramide relative to palmitic acid (C16:0) or docosahexaenoic acid (C22:6n-3) infusion; (2) assess whether the abomasal infusion of choline chloride or l-serine elevated hepatic phosphatidylcholine (PC) in cows abomasally infused with C16:0; and (3) characterize the PC lipidome in cows abomasally infused with C22:6n-3, relative to C16:0 or C22:0 infusion. In a 5 × 5 Latin square design, 5 rumen-cannulated Holstein cows (214 ± 4.9 DIM; 3.2 ± 1.1 parity) were enrolled in a study with 6-d periods. Abomasal infusates consisted of (1) palmitic acid (PA; 98% C16:0); (2) PA + choline chloride (PA+C; 50 g/d choline chloride); (3) PA + l-serine (PA+S; 170 g/d l-serine); (4) behenic acid (BA; 92% C22:0); and (5) an algal oil rich in docosahexaenoic acid (DHA; 44% C22:6n-3). Emulsion infusates provided 301 g/d of total fatty acids containing a minimum of 40 g/d of C16:0. Cows were fed a corn silage-based diet. Milk was collected on d -2, -1, 5, and 6. Blood was collected and liver biopsied on d 6 of each period. Although we did not detect differences in milk yield, milk fat yield and content were lower in cows infused with DHA relative to PA. Plasma triacylglycerol concentrations were lower with DHA treatment relative to PA or BA. Cows infused with DHA had lower plasma insulin concentrations relative to cows infused with PA only. For objective 1, hepatic ceramide-d18:2/22:0 was highest in cows infused with BA relative to other treatments. For objective 2, plasma free choline concentrations were greater in PA+C cows relative to PA; however, we did not observe this effect with PA+S. Plasma total PC concentrations were similar for all treatments. Regarding the hepatic lipidome, a total of 18 hepatic PC were higher (e.g., PC-16:1/18:2) and 25 PC were lower (e.g., PC-16:0/22:6) with PA+C infusion relative to PA. In addition, 17 PC were higher (e.g., PC-20:3/22:5) and 21 PC were lower (e.g., PC-18:0/22:6) with PA+S infusion relative to PA. For objective 3, hepatic concentrations of many individual saturated PC (e.g., PC-18:0/15:0) were lower with DHA relative to other treatments. Hepatic concentrations of highly unsaturated PC with very-long-chain fatty acids (e.g., PC-14:0/22:6) were higher in DHA-infused cows relative to PA, PA+C, PA+S, or BA. The abomasal infusion of emulsions containing palmitic acid, palmitic acid with choline chloride or serine, behenic acid, or docosahexaenoic acid influence the hepatic ceramide and PC profiles of lactating cows.

Lower Postprandial Lipemia After Palmitic Acid-rich Fats with and Without Interesterification Is Associated with Increased Atherogenic Lipoproteins versus a High MUFA Oil (OR19-03-19)

ObjectivesInteresterified (IE) fats are commonly used as hard fat alternatives to trans fats. However, their health effects are unknown. Postprandial lipemia is an independent risk factor for CVD; a prolonged postprandial lipemia may detrimentally impact lipoprotein remodelling. We compared the postprandial lipoprotein profiles of palmitic acid-rich IE and non-IE fats and an unsaturated control oil. MethodsA double blind, randomized controlled trial in healthy adults (n = 20) aged 45–75 years, assessed effects of single test meals (897 kcal, 50 g fat, 16 g protein, 88 g carbohydrate) on postprandial plasma triacylglycerol (TG) concentrations by colorimetric assay and lipoprotein profiles by NMR. Test fats were: a commonly consumed IE [80:20 palm stearin/palm kernel fat], the equivalent non-IE fat, and a control high-MUFA rich oil (canola oil, CO) as a reference point. Blood was collected at baseline, and hourly thereafter for 8h. Lipoprotein statistical analysis used linear mixed effect regression modelling (lme4 package on R). Metabolites were considered as response and treatment as predictor along with various covariates: time, period, baseline values, and subject (random effect), with post hoc adjustment for multiple comparisons. ResultsThere was a significant time x treatment interaction (P = 0.006) in change from baseline for plasma TG concentrations (Figure 1), with significant differences between the IE fat and CO and the non-IE fat and CO (both P = 0.001), but no difference between IE and non-IE fats. NMR analysis of lipoprotein (VLDL, HDL, LDL) particle size, composition and number, revealed an increase in particle and cholesterol concentrations following IE and non-IE fats versus the CO at T + 8h for the following lipoprotein fractions: chylomicron remnants and extremely large VLDL (non-IE vs CO P < 0.05; IE vs CO P < 0.001; Figure 2), and very large VLDL (non-IE vs CO P < 0.01; IE vs CO P < 0.005). ConclusionsInteresterification of a commonly consumed palm-based fat did not modify lipoprotein particle size or composition. Despite a reduction in postprandial lipemia, the generation of atherogenic TG-rich lipoprotein remnant particles in the late postprandial phase may in part explain the atherogenic potential of saturated rich fats compared with unsaturated rich fats. Funding SourcesBBSRC DRINC, UK. Supporting Tables, Images and/or Graphs▪▪

The effect of the dietary inclusion levels and sources of zinc on the performance, metabolism, redox and immune status of turkeys

The aim of this experiment was to determine whether the inclusion levels of supplemental Zn in turkey diets could be reduced without compromising important metabolic functions, the immune status and growth parameters of birds, and whether the above goal can be achieved with the use of zinc (Zn) nanoparticles. The experiment was performed on 648 one-day-old Hybrid Converter turkey hens divided into 6 groups with 6 replicates (18 birds per pen), in a two-factorial design with three dietary supplemental levels of Zn (100, 50 and 10 mg/kg) and two dietary sources of Zn - conventional zinc oxide (ZnO) and Zn nanoparticles (NP-ZnO). The applied inclusion levels and sources of Zn had no effect on the growth performance of turkeys, including liveability. The replacement of ZnO with NP-ZnO in turkey diets led to an increase in the levels of albumin (ALB), triacylglycerols (TG) and alkaline phosphatase (ALP) activity in the blood serum as well as minor changes in redox indicators including a decrease in plasma malondialdehyde (MDA) levels, catalase (CAT) activity in the liver, and total glutathione (GSH + GSSG) and MDA levels in the bursa of Fabricius. The addition of 50 mg and 100 mg of Zn exerted similar effects on blood biochemical parameters and antioxidant status indicators in the liver. Only in the bursa of Fabricius, the moderate dietary inclusion level of Zn contributed to a decrease in GSH + GSSG levels. The results of this study indicate that the recommended level of ZnO supplementation in turkey diets can be reduced to 50 mg/kg. A decrease in the dose of supplemental Zn from 100 to 10 mg/kg did not compromise the growth performance of turkeys, but it had a negative effect on lipid metabolism by increasing plasma TG concentrations. The replacement of ZnO with NP-ZnO had no beneficial influence on performance, the immune and antioxidant status of turkeys.

Insect Meal as Alternative Protein Source Exerts Pronounced Lipid-Lowering Effects in Hyperlipidemic Obese Zucker Rats

Specific dietary proteins exert strong health-related effects compared with casein. Herein, the hypothesis was tested using screening and conventional biochemical and molecular biological techniques that protein-rich insect meal compared with casein influences metabolic health in hyperlipidemic rats. A 4-wk feeding trial with male, 8-wk-old homozygous obese Zucker rats (n=36) and male, 8-wk-old heterozygous lean Zucker rats (n=12) was performed. Obese rats were randomly divided into 3 obese groups (OC, OI50, and OI100) of 12 rats each and lean rats served as a lean control group (LC). LC and OC were fed a control diet with 20% casein as protein source, whereas in OI50 and OI100 50% and 100% of the casein, respectively, was replaced isonitrogenously by insect meal from Tenebrio molitor L. All data were analyzed by 1-factor ANOVA, except transcriptomic data which were analyzed by groupwise comparisons with the OC group. Transcript profiling revealed a coordinated inhibition by -17% to -521% and -37% to -859% of genes involved in fatty acid, triacylglycerol (TG), and cholesterol biosynthesis in the livers of OI100 and OI50, respectively, compared with OC (P<0.05). Enzyme activities of fatty acid synthase, glucose-6 phosphate dehydrogenase, and 3-hydroxy-3-methylglutaryl-coenzyme-A reductase in the liver were 100-150% greater in OC compared with LC, but reduced by 50-60% in OI100 compared with OC (P<0.05), to the same level as in LC. Liver and plasma concentrations of TG and cholesterol were 250-1000%, 30-800%, and 40-600% higher in OC, OI50, and OI100, respectively, than in LC (P<0.05), but 40-60% and 20-60% lower in OI100 and OI50, respectively, than in group OC (P<0.05). Plasma and liver concentrations of homocysteine were 20-30% lower in group OI100 than in group OC (P<0.05). Insect meal exerts pronounced lipid-lowering effects in hyperlipidemic rats and, thus, might be useful for hyperlipidemic individuals.

Roux-en-Y Gastric Bypass Surgery Induces Distinct but Frequently Transient Effects on Acylcarnitine, Bile Acid and Phospholipid Levels

Roux-en-Y gastric bypass (RYGB) is an effective method to achieve sustained weight loss, but the mechanisms responsible for RYGB effects have not yet been fully characterized. In this study, we profiled the concentrations of 143 lipid metabolites in dry blood spots (DBS) of RYGB patients. DBS from obese patients (BMI range 35–44 kg/m2) were collected 7 days before, 15 and 90 days after the surgery. LC-MS/MS was used to quantify acylcarnitines, phosphatidylcholines, sphingomyelins and bile acids. RYGB caused a rapid increase in acylcarnitine levels that proved to be only transient, contrasting with the sustained decrease in phosphatidylcholines and increase of sphingomyelins and bile acids. A PLS-DA analysis revealed a 3-component model (R2 = 0.9, Q2 = 0.74) with key metabolites responsible for the overall metabolite differences. These included the BCAA-derived acylcarnitines and sphingomyelins with 16 and 18 carbons. We found important correlations between the levels of BCAA-derived acylcarnitines and specific sphingomyelins with plasma cholesterol and triacylglycerol concentrations. Along with the marked weight loss and clinical improvements, RYGB induced specific alterations in plasma acylcarnitines, bile acid and phospholipid levels. This calls for more studies on RYGB effects aiming to elucidate the metabolic adaptations that follow this procedure.

Supplementation effects of pomegranate by-products on oxidative status, metabolic profile, and performance in transition dairy cows

Recent studies demonstrated a high antioxidant capacity for pomegranate components due to their rich bioactive compounds, such as conjugated fatty acids and phenolics. The objective of the present study was, therefore, to assess whether pomegranate seed or pomegranate seed pulp (peel + seed) supplementation could be effective to improve antioxidant status, and hence metabolic profile and performance in periparturient dairy cows. After a 1-wk pretreatment period, Holstein cows (primiparous n = 12, multiparous n = 18) were assigned to 3 dietary treatments from 25 d before expected calving through 25 d postcalving. The dietary treatments included (1) control (CON); (2) diet supplemented with pomegranate seeds (PS; 400 g/cow per day); and (3) diet supplemented with pomegranate seed pulp (PSP; 400 g of seeds/cow per day + 1200 g of peels/cow per day). Compared with CON, supplementation with either PS or PSP had no effects on dry matter intake, rumen fermentation, and plasma concentrations of cholesterol, total protein, globulin, and aspartate amino transferase, but enhanced plasma total antioxidant activity, and lowered triacylglycerol, free fatty acids (FFA), and β-hydroxybutyrate at both pre- and postpartum periods. Plasma concentration of glucose, albumin, malondialdehyde (MDA) and blood superoxide dismutase (SOD) activity were not affected by dietary treatments at prepartum, whereas SOD activity increased and glucose, albumin, MDA, and FFA-to-albumin ratio decreased by feeding both by-products at postpartum period. In contrast to PS, supplementing PSP resulted in a greater decrease in plasma glucose and triacylglycerol concentration and higher increase in SOD activity. Energy- and fat-corrected milk yields were higher in cows fed PSP diet compared with those fed CON or PS diets, but content of milk fat, protein, and lactose were similar across the dietary treatments. These findings indicated that dietary pomegranate by-products supplementation, in particular PSP, could improve antioxidant status, which was associated with a decline in lipid oxidation (FFA and β-hydroxybutyrate) and peroxidation (MDA) and an enhancement in glucose utilization as well as fat-corrected milk yield.

Liver lipid metabolism disruption in cancer cachexia is aggravated by cla supplementation -induced inflammation

The liver is the main organ regulating metabolism. In spite of that, few studies examine liver metabolism in cachexia, a wasting syndrome associated with increased morbidity and mortality in cancer. Cachexia induces major metabolic disruption, inflammation and fat and lean mass loss. We have previously shown impairment of hepatic lipid metabolism in cancer cachexia that contributes to the aggravation of the symptoms. The present study addresses the effects of Conjugated Linoleic Acid supplementation upon liver lipid metabolism in cachectic rats. Male Wistar rats were randomly assigned to control groups (C) receiving 0.9NaCl (Placebo CP); or to groups supplemented with sunflower oil (CSF), supplemented with CLA (CCLA), or still, to tumour bearing animals (T) receiving NaCl (TP), sunflower oil (TSF), or CLA (TCLA). Supplementation (0.5ml) by gavage was carried out for 14 days. Body weight, dietary intake, glucose, cholesterol and triacylglycerol plasma content, liver glycogen and triacylglycerol content and mRNA expression of liver carnitine palmitoyltransferase I and II (CPT I and II), as well as microsomal triglyceride transfer protein (MTP), liver fatty acid-binding protein (L-FABP), peroxisome proliferator-activated receptor-alpha (PPAR-alpha), and apolipoprotein B (apoB), were assessed. Liver CPT II activity was reduced in all groups, when compared with CP. Hepatic mRNA expression of MTP, apoB and FABP was reduced in TCLA, when compared with all groups. TCLA also presented increased hepatic and plasma triacylglycerol content, when compared with all T groups. Adipose tissue-derived inflammatory factors were assessed. No differences among the groups were observed in regard to Retro Peritoneal Adipose Tissue cytokine (IL-1β, IL-6, and TNF-α) protein content and expression, with the exception of IL-10 in tumour-bearing animals. In the Epididymal Adipose Tissue, the inflammatory cytokines were augmented in TCLA, compared with all other groups. CLA supplementation fails to promote the re-establishment of hepatic lipid metabolism in tumour-bearing animals, and therefore is not recommended in cancer-related cachexia.