Reduced Plasma Triacylglycerol Research Articles

Effect of Dietary Acetic Acid Supplementation on Plasma Glucose, Lipid Profiles, and Body Mass Index in Human Adults: A Systematic Review and Meta-analysis

BackgroundAcetic acid is a short-chain fatty acid that has demonstrated biomedical potential as a dietary therapeutic agent for the management of chronic and metabolic illness comorbidities. In human beings, its consumption may improve glucose regulation and insulin sensitivity in individuals with cardiometabolic conditions and type 2 diabetes mellitus. Published clinical trial evidence evaluating its sustained supplementation effects on metabolic outcomes is inconsistent. ObjectiveThis systematic review and meta-analysis summarized available evidence on potential therapeutic effects of dietary acetic acid supplementation via consumption of acetic acid–rich beverages and food sources on metabolic and anthropometric outcomes. MethodsA systematic search was conducted in Medline, Scopus, EMBASE, CINAHL Plus, and Web of Science from database inception until October 2020. Randomized controlled trials conducted in adults evaluating the effect of dietary acetic acid supplementation for a minimum of 1 week were included. Meta-analyses were performed using a random-effects model on fasting blood glucose (FBG), triacylglycerol (TAG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), glycated hemoglobin (HbA1c), body mass index (BMI), and body fat percentage. Statistical heterogeneity was assessed by calculation of Q and I2 statistics, and publication bias was assessed by calculation of Egger’s regression asymmetry and Begg’s test. ResultsSixteen studies were included, involving 910 participants who consumed between 750 and 3600 mg acetic acid daily in interventions lasting an average of 8 weeks. Dietary acetic acid supplementation resulted in significant reductions in TAG concentrations in overweight and obese but otherwise healthy individuals (mean difference [MD] = −20.51 mg/dL [95% confidence intervals = −32.98, −8.04], P = .001) and people with type 2 diabetes (MD = −7.37 mg/dL [−10.15, −4.59], P < .001). Additionally, acetic acid supplementation significantly reduced FBG levels (MD = −35.73 mg/dL [−63.79, −7.67], P = .01) in subjects with type 2 diabetes compared with placebo and low-dose comparators. No other changes were seen for other metabolic or anthropometric outcomes assessed. Five of the 16 studies did not specify the dose of acetic acid delivered, and no studies measured blood acetate concentrations. Only one study controlled for background acetic acid-rich food consumption during intervention periods. Most studies had an unclear or high risk of bias. ConclusionSupplementation with dietary acetic acid is well tolerated, has no adverse side effects, and has clinical potential to reduce plasma TAG and FBG concentrations in individuals with type 2 diabetes, and to reduce TAG levels in people who are overweight or obese. No significant effects of dietary acetic acid consumption were seen on HbA1c, HDL, or anthropometric markers. High-quality, longer-term studies in larger cohorts are required to confirm whether dietary acetic acid can act as an adjuvant therapeutic agent in metabolic comorbidities management.

Plasma triacylglycerol-reducing activity of ergosterol linolenate is associated with inhibition of intestinal lipid absorption

Abstract This study investigated the role of ergosterol linolenate in the alleviation of hyperlipidemia induced by a high-fat diet and further explored the expression of key genes involved in lipid absorption and metabolism in mice. Twenty-four male C57BL/6J mice were divided into three groups and fed one of three experimental diets: a high-fat diet (HF), or a HF diet with either ergosterol (ER) or ergosterol linolenate (EL), respectively, for 6 weeks. The results demonstrate that EL significantly reduced plasma triacylglycerol (TG) levels by 20%, weight gain by 50% and relative perirenal and epididymal fat by 23.6%. This was accompanied by a significant decrease in liver cholesterol, liver total fatty acids and fecal bile acids, accompanied by a marked increase in fecal total fatty acids. Ergosterol linolenate effectively counteracted steatosis induced by a high-fat diet. Ergosterol linolenate also altered the mRNA expression of key intestinal and hepatic genes involved in lipid absorption and metabolism. Of them, ergosterol linolenate significantly reduced the mRNA expression of intestinal microsomal triglyceride transfer protein (MTP), a key component in the formation of chylomicrons. Therefore, the plasma TG-reducing action of ergosterol linolenate can be largely attributed to reduced lipid absorption and increased fecal lipid excretion.

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.

Reduction in voluntary food intake, but not fasting, stimulates hypothalamic gonadotropin-inhibitory hormone precursor mRNA expression in chicks under heat stress

Heat stress is an issue of rising concern across the globe. Recently, we found that mRNA expression of gonadotropin-inhibitory hormone (GnIH), an orexigenic neuropeptide, was increased in the heat-exposed chick brain when food intake was reduced. The aim of the current study was to examine mRNA expression of GnIH and of the glucocorticoid receptors (GRs) in the hypothalamus as well as the plasma corticosterone (CORT) and metabolites in 14-d-old chicks exposed to a high ambient temperature (HT; 40 ± 1 °C for 1 or 5 h) or a control thermoneutral temperature (CT; 30 ± 1 °C), either with free access to food or fasted. Heat stress caused a voluntary reduction of food intake and reduced plasma triacylglycerol concentration, but increased rectal temperature and plasma CORT and glucose concentrations (P < 0.05). Heat stress also increased (P < 0.05) the expression of diencephalic GnIH mRNA in chicks when they reduced food intake voluntarily, but did not do so under fasting conditions. Although the expression of GR mRNA was not altered as a result of heat stress, its expression was decreased (P < 0.05) in fasted chicks at 5 h in comparison with fed chicks. In addition, the rectal temperature of fasted chicks was lower than that of fed chicks under both CT and HT. In conclusion, voluntary reduction of food intake caused an increase in brain GnIH mRNA expression, plasma CORT, and body temperature in chicks under heat stress. Interestingly, brain GnIH mRNA expression was not induced by heat stress in fasted chicks and was not accompanied by a decrease in rectal temperature. These results suggest that the increased expression of brain GnIH mRNA in chicks under heat stress could be a consequence of a mechanism mediated by the voluntary reduction of food intake, but that it is not a consequence of fasting.

ARB treatment ameliorates triacylglycerol accumulation during insulin‐resistant conditions in the liver of OLETF rats

Non‐alcoholic fatty liver disease (NAFLD) is a growing concern globally, and is associated with obesity, hyperlipemia, hypertension, insulin resistance, and diabetes; all traits linked to metabolic syndrome, which affects 20% of the US population. While angiotensin receptor blockers (ARB) effectively ameliorate the hypertension associated with metabolic disorders, its potential benefits on other aspects of metabolism during such conditions are not fully appreciated. ARB treatment may reduce overproduction and accumulation of hepatic triacylglycerols (TG), but it remains unknown whether ARB treatment has favorable effects in fatty livers associated with insulin resistance. To evaluate the benefits of the ARB treatment on lipid‐related genes, three groups (n=4–6) of 25‐week‐old rats were used: (1) LETO (lean strain‐control), (2) insulin resistant OLETF, and 3) OLETF + ARB (10 mg olmesartan/kg/d × 8 wks). An oral glucose tolerance test (oGTT) was performed to mimic a high glucose challenge. Liver and plasma were collected at T0, T30, and T60 min of the oGTT. We measured gene expression of hepatic PPARα, SREBP1c, FASN, and CPT1 along with TG and cholesterol levels in liver and plasma. PPARα expression was 1.6‐fold lower at T0 in OLETF+ARB compared with OLETF, but no changes were detected for other genes evaluated. Hepatic TG content was 1.5‐, 3.4‐ and 1.5‐fold lower at T0, T30, and T60, respectively, in OLETF+ARB compared to OLETF, along with 1.2‐fold lower plasma TG at T30. These changes suggest that AT1 signaling contributes to stabilizing lipid metabolism especially during a glucose challenge, and contributes to maintaining lower hepatic TG content that translates to reduced plasma TG during a glucose challenge.Support or Funding InformationM. Thorwald was supported by NIH NCMHD9T37MD001480. R.M. Ortiz was partially supported by NIH NHLBIK02HL103787. Research was partially funded by NIH NHLBIR01HL091767.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Caffeic acid and hydroxytyrosol have anti-obesogenic properties in zebrafish and rainbow trout models.

Some natural products, known sources of bioactive compounds with a wide range of properties, may have therapeutic values in human health and diseases, as well as agronomic applications. The effect of three compounds of plant origin with well-known dietary antioxidant properties, astaxanthin (ATX), caffeic acid (CA) and hydroxytyrosol (HT), on zebrafish (Danio rerio) larval adiposity and rainbow trout (Onchorynchus mykiss) adipocytes was assessed. The zebrafish obesogenic test (ZOT) demonstrated the anti-obesogenic activity of CA and HT. These compounds were able to counteract the obesogenic effect produced by the peroxisome proliferator-activated receptor gamma (PPARγ) agonist, rosiglitazone (RGZ). CA and HT suppressed RGZ-increased PPARγ protein expression and lipid accumulation in primary-cultured rainbow trout adipocytes. HT also significantly reduced plasma triacylglycerol concentrations, as well as mRNA levels of the fasn adipogenic gene in the adipose tissue of HT-injected rainbow trout. In conclusion, in vitro and in vivo approaches demonstrated the anti-obesogenic potential of CA and HT on teleost fish models that may be relevant for studying their molecular mode of action. Further studies are required to evaluate the effect of these bioactive components as food supplements for modulating adiposity in farmed fish.

Lysosomal acid lipase regulates VLDL synthesis and insulin sensitivity in mice.

Aims/hypothesisLysosomal acid lipase (LAL) hydrolyses cholesteryl esters and triacylglycerols (TG) within lysosomes to mobilise NEFA and cholesterol. Since LAL-deficient (Lal-/-) mice suffer from progressive loss of adipose tissue and severe accumulation of lipids in hepatic lysosomes, we hypothesised that LAL deficiency triggers alternative energy pathway(s).MethodsWe studied metabolic adaptations in Lal-/- mice.ResultsDespite loss of adipose tissue, Lal-/- mice show enhanced glucose clearance during insulin and glucose tolerance tests and have increased uptake of [3H]2-deoxy-D-glucose into skeletal muscle compared with wild-type mice. In agreement, fasted Lal-/- mice exhibit reduced glucose and glycogen levels in skeletal muscle. We observed 84% decreased plasma leptin levels and significantly reduced hepatic ATP, glucose, glycogen and glutamine concentrations in fed Lal-/- mice. Markedly reduced hepatic acyl-CoA concentrations decrease the expression of peroxisome proliferator-activated receptor α (PPARα) target genes. However, treatment of Lal-/- mice with the PPARα agonist fenofibrate further decreased plasma TG (and hepatic glucose and glycogen) concentrations in Lal-/- mice. Depletion of hepatic nuclear factor 4α and forkhead box protein a2 in fasted Lal-/- mice might be responsible for reduced expression of microsomal TG transfer protein, defective VLDL synthesis and drastically reduced plasma TG levels.Conclusions/interpretationOur findings indicate that neither activation nor inactivation of PPARα per se but rather the availability of hepatic acyl-CoA concentrations regulates VLDL synthesis and subsequent metabolic adaptations in Lal-/- mice. We conclude that decreased plasma VLDL production enhances glucose uptake into skeletal muscle to compensate for the lack of energy supply.Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-016-3968-6) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

Krill oil reduces plasma triacylglycerol level and improves related lipoprotein particle concentration, fatty acid composition and redox status in healthy young adults - a pilot study

BackgroundLipid abnormalities, enhanced inflammation and oxidative stress seem to represent a vicious circle in atherogenesis, and therapeutic options directed against these processes seems like a reasonable approach in the management of atherosclerotic disorders. Krill oil (RIMFROST Sublime®) is a phospholipid-rich oil with eicosapentaenoic acid (EPA): docosahexaenoic acid (DHA) ratio of 1.8:1. In this pilot study we determined if krill oil could favourable affect plasma lipid parameters and parameters involved in the initiation and progression of atherosclerosis.MethodsThe study was conducted as a 28 days intervention study examining effect-parameters of dietary supplementation with krill oil (832.5 mg EPA and DHA per day). 17 healthy volunteers in the age group 18–36 (mean age 23 ± 4 years) participated. Plasma lipids, lipoprotein particle sizes, fatty acid composition in plasma and red blood cells (RBCs), plasma cytokines, antioxidant capacity, acylcarntines, carnitine, choline, betaine, and trimethylamine-N-oxide (TMAO) were measured before and after supplementation.ResultsPlasma triacylglycerol (TAG) and large very-low density lipoprotein (VLDL) & chylomicron particle concentrations decreased after 28 days of krill oil intake. A significant reduction in the TAG/HDL cholesterol resulted. Krill oil supplementation decreased n-6/n-3 polyunsaturated fatty acids (PUFA) ratio both in plasma and RBCs. This was due to increased EPA, DHA and docosapentaenoic acid (DPA) and reduced amount of arachidonic acid (AA). The increase of n-3 fatty acids and wt % of EPA and DHA in RBC was of smaller magnitude than found in plasma. Krill oil intake increased the antioxidant capacity, double bond index (DBI) and the fatty acid anti-inflammatory index. The plasma atherogenicity index remained constant whereas the thrombogenicity index decreased. Plasma choline, betaine and the carnitine precursor, γ-butyrobetaine were increased after krill oil supplementation whereas the TMAO and carnitine concentrations remained unchanged.ConclusionKrill oil consumption is considered health beneficial as it decreases cardiovascular disease risk parameters through effects on plasma TAGs, lipoprotein particles, fatty acid profile, redox status and possible inflammation. Noteworthy, no adverse effects on plasma levels of TMAO and carnitine were found.

Stimulation of Adipose Tissue Lipoprotein Lipase Activity Improves Glucose Metabolism and Increases High Density Lipoprotein Cholesterol in the Spontane

Insulin resistance syndrome (IRS), high blood pressure, elevated blood glucose and triacylglycerol-rich lipoproteins (TG-RL), as well as low levels of high-density lipoprotein (HDL-C) are disorders that combine to define metabolic syndrome (MetS). Metabolic syndrome is on the rise in the United States and is believed to be a powerful predictor of risk for diabetes and coronary events. Modulation of the activity of lipoprotein lipase (LPL) in MetS affects lipolysis of TG-RL, which has a direct correlation with the levels of plasma HDL-C. This study examined if increasing LPL activity by dietary means in a model for MetS leads to reduced IRS and increase in plasma HDL-C concentration. Ninety day-old Spontaneously Hypertensive Stroke-Prone male rats were originally fed lab chow diet for seven days. This was followed by feeding a fatty acid diet for 7 days containing one of the following: triolein (TO), trans fatty acids-rich (TFA, margarine) and 0 fatty acids (Control) with /without an LPL-rising drug (NO-1866) by gavages (5 mg or 25 mg/kg b. wt.). The results show that blood glucose and triacylglycerol levels were decreased with NO-1886. HDL-C levels increased with NO-1866 in the control and triolein group but not in the TFA group. Animals in the triolein group had higher levels of phospholipids and lower levels of insulin. Inclusion of NO-1866 lowered HOMA-IR by almost 40% in the control and the TFA group, but no further reduction was observed in the TO group. The control TFA groups had up to 45% higher HOMA-IR than the TO group. Overall the data suggest that raising the activity of lipoprotein lipase by dietary means, including the feeding of monounsaturated fat may increase HDL-C, reduce plasma triacylglycerol and other indices of MetS risk, and thus may decrease the incidence of vascular complications through the normalization of lipid metabolism in subjects with MetS.

Plasma triacylglycerol‐lowering activity of citrus polymethoxylated flavones is mediated by modulating the genes involved in lipid metabolism in hamsters

The present study investigated the underlying mechanism by which citrus polymethoxylated flavones (PMF) reduced plasma triacylglycerols (TG) in hamsters. Four groups of male hamsters were given a non‐cholesterol diet (NCD), a high cholesterol diet (HCD), a high cholesterol diet with supplementation of 0.5% PMF (L‐PMF), and a high cholesterol diet with supplementation of 1.0% PMF (H‐PMF), respectively, for 8 weeks. Results showed PMF could lower plasma TG by 32–46%, but it had no effect on plasma cholesterol. This was accompanied by down‐regulation of mRNA of liver sterol regulatory element binding protein‐1c (SREBP1c), fatty acid synthase (FAS), and peroxisome proliferator activated receptor alpha (PPARα) while up‐regulation of liver lipoprotein lipase (LPL). In addition, dietary PMF increased cholesterol by 5–15% and total lipids by 34–43% in the liver. PMF supplementation also reduced the body weight gain and the relative weights of white adipose tissue pads by 23–39%, possibly by decreasing the gene expression of FAS and LPL in the epididymal fat pad. It was concluded that plasma TG‐lowering activity of dietary PMF was mediated by modulating genes involved in lipid metabolism in hamsters.Practical applications: Hyperlipidemia is one of the risk factors for coronary heart diseases. The present study found that polymethoxylated flavones (PMF) were effective in reducing plasma triacylglycerols and adipose tissue weight. PMF may be developed as a nutraceutical to prevent hyperlipidemia and obesity.Citrus polymethoxylated flavones are able to reduce plasma triacylglycerols via two mechanisms of inhibition of lipogenesis and enhancement of lipid uptake by the liver, most likely mediated by down‐regulation of SREBP1c and FAS along with up‐regulation of LPL in the liver.

A Phospholipid-Protein Complex from Krill with Antioxidative and Immunomodulating Properties Reduced Plasma Triacylglycerol and Hepatic Lipogenesis in Rats.

Dietary intake of marine omega-3 polyunsaturated fatty acids (n-3 PUFAs) can change the plasma profile from atherogenic to cardioprotective. In addition, there is growing evidence that proteins of marine origin may have health benefits. We investigated a phospholipid-protein complex (PPC) from krill that is hypothesized to influence lipid metabolism, inflammation, and redox status. Male Wistar rats were fed a control diet (2% soy oil, 8% lard, 20% casein), or diets where corresponding amounts of casein and lard were replaced with PPC at 3%, 6%, or 11% (wt %), for four weeks. Dietary supplementation with PPC resulted in significantly lower levels of plasma triacylglycerols in the 11% PPC-fed group, probably due to reduced hepatic lipogenesis. Plasma cholesterol levels were also reduced at the highest dose of PPC. In addition, the plasma and liver content of n-3 PUFAs increased while n-6 PUFAs decreased. This was associated with increased total antioxidant capacity in plasma and increased liver gene expression of mitochondrial superoxide dismutase (Sod2). Finally, a reduced plasma level of the inflammatory mediator interleukin-2 (IL-2) was detected in the PPC-fed animals. The present data show that PPC has lipid-lowering effects in rats, and may modulate risk factors related to cardiovascular disease progression.

A water-soluble extract of chicken reduced plasma triacylglycerols, but showed no anti-atherosclerotic activity in apoE−/− mice

BackgroundA water-soluble protein extract of chicken (CP) has been reported to modulate plasma lipids and hepatic lipid catabolism. Atherosclerosis is the primary contributing factor of cardiovascular disease and there is evidence that both lipid abnormalities and chronic inflammation have crucial involvement in the initiation and progression of atherosclerosis. The aim of the study was to assess the impact of CP on atherosclerotic development in mice predisposed for developing atherosclerotic lesions. Methods24 apoE−/− mice were divided into two groups and fed a high-fat diet. The control group received a 20% casein diet, whereas the intervention group was fed a diet with 15% chicken protein and 5% casein. Body weight and feed intake was measured regularly, and indirect calorimetry was measured at week 1 and 10. After 12 weeks the mice were sacrificed, and blood, liver, heart and aorta were harvested. Plasma and liver lipids and fatty acid composition analyses were carried out, in addition to gene expression in liver and heart. Also, en-face analysis was performed on aorta, and plasma inflammatory markers were determined. ResultsThe dietary intervention with CP only resulted in minor reduction of plasma triacylglycerol (TAG) and no change in the plasma cholesterol level compared to control. The TAG lowering was associated with induction of hepatic carnitine acyltransferase 2 activity and gene expression. Mice fed CP also displayed a lower respiratory exchange ratio during the light cycle, indicating a higher degree of fatty acid oxidation in the fasting state. Aorta images displayed no differences in plaque development between mice fed CP or control diet, and gene expression of inflammatory markers in heart was unchanged. Moreover, CP administration did not influence plasma levels of several inflammatory cytokines and chemokines in apoE−/− mice. ConclusionChicken protein displayed a slight potential to increase mitochondrial fatty acid oxidation and reduce plasma TAG. However, CP did not affect plasma cholesterol levels, inflammation status or atherosclerotic development in apoE−/− mice. Based on these results, dietary intervention with CP does not have sufficient capacity to influence atherosclerotic development in apoE−/− mice.

Krill protein hydrolysate reduces plasma triacylglycerol level with concurrent increase in plasma bile acid level and hepatic fatty acid catabolism in high-fat fed mice

Background: Krill powder, consisting of both lipids and proteins, has been reported to modulate hepatic lipid catabolism in animals. Fish protein hydrolysate diets have also been reported to affect lipid metabolism and to elevate bile acid (BA) level in plasma. BA interacts with a number of nuclear receptors and thus affects a variety of signaling pathways, including very low density lipoprotein (VLDL) secretion. The aim of the present study was to investigate whether a krill protein hydrolysate (KPH) could affect lipid and BA metabolism in mice. Method: C57BL/6 mice were fed a high-fat (21%, w/w) diet containing 20% crude protein (w/w) as casein (control group) or KPH for 6 weeks. Lipids and fatty acid composition were measured from plasma, enzyme activity and gene expression were analyzed from liver samples, and BA was measured from plasma.Results: The effect of dietary treatment with KPH resulted in reduced levels of plasma triacylglycerols (TAG) and non-esterified fatty acids (NEFAs). The KPH treated mice had also a marked increased plasma BA concentration. The increased plasma BA level was associated with induction of genes related to membrane canalicular exporter proteins (Abcc2, Abcb4) and to BA exporters to blood (Abcc3 and Abcc4). Of note, we observed a 2-fold increased nuclear farnesoid X receptor (Fxr) mRNA levels in the liver of mice fed KPH. We also observed increased activity of the nuclear peroxiosme proliferator-activated receptor alpha (PPARα) target gene carnitine plamitoyltransferase 2 (CPT-2). Conclusion: The KPH diet showed to influence lipid and BA metabolism in high-fat fed mice. Moreover, increased mitochondrial fatty acid oxidation and elevation of BA concentration may regulate the plasma level of TAGs and NEFAs.Key words: Krill protein hydrolysate, triacylglycerol, fatty acids, TNFα

Acute oral amino acid intake increases both secretion and breakdown of very low density lipoprotein‐triacylglycerol

We have previously reported a reduced plasma triacylglycerol (TAG) concentration in elderly individuals following chronic intake of amino acids (AAs), but it is unclear how acute intake of AAs affects plasma TAG kinetics. We used dual stable isotope tracer methodology in this study to investigate the effect of acute AA intake on the fractional secretion rate (FSR) and fractional breakdown rate (FBR) of VLDL‐TAG derived from plasma fatty acids. Eight hypertriacylglycerolaemic volunteers (mean ± standard deviation (SD): age 63.4 ± 7.7 years; BMI 29.6 ± 5.0 kg·m−2; fasting TAG 191 ± 52 mg·dl−1) were studied during a 5‐h basal period and a 5‐h period of acute AA intake. Infusions of U‐13C16‐palmitate and 2H2‐palmitate were started and stopped at specific time points to allow VLDL‐TAG secretion and breakdown to be calculated. VLDL‐TAG FSR was significantly higher during the AA intake period than during the basal period (mean ± SEM: 12.9 ± 2.6 vs. 8.7 ± 1.4 %·h−1; P &lt; 0.05), as was VLDL‐TAG FBR (13.8 ± 4.0 vs. 4.9 ± 1.6 %·h−1; P &lt; 0.05). We conclude that acute amino acid intake increases fractional secretion and breakdown rates of VLDL‐TAG, and may promote a state of net breakdown, which lowers the plasma TAG concentration. The study is sponsored by 1R01 AG033761 NIH/NIA and P30 AG024832 NIH/NIA. Screenings and study visits are being undertaken within the ITS‐Clinical Research Center at UTMB, funded by grant 1 U54RR026141 NIH/NCRR.

Intake of mulberry 1-deoxynojirimycin prevents diet-induced obesity through increases in adiponectin in mice

In this study, the anti-obesity effect of 1-deoxynojirimycin (DNJ) was examined in the diet-induced obese mouse model. Mulberry DNJ was administered to the obese mice for 12weeks. As a result, DNJ decreased both the visceral fat weight and adipocyte size. To determine the influence of DNJ on lipid metabolism, lipid parameters of the plasma and the liver and the activities of several molecules related to lipid metabolism in the liver were measured. DNJ activated the β-oxidation system, suppressed lipid accumulation in the liver and reduced plasma triacylglycerol. Since it was thought that the factor activated in the β-oxidation system was adiponectin, plasma adiponectin levels were measured and it was shown that plasma adiponectin was increased with DNJ. Therefore, it was suggested that DNJ promoted an increase in plasma adiponectin and activated the β-oxidation system. Overall, it was shown that DNJ prevents diet-induced obesity through an increase in adiponectin.

Liver specific inactivation of carboxylesterase 3/triacylglycerol hydrolase decreases blood lipids without causing severe steatosis in mice

Carboxylesterase 3/triacylglycerol hydrolase (Ces3/TGH) participates in hepatic very low-density lipoprotein (VLDL) assembly and in adipose tissue basal lipolysis. Global ablation of Ces3/Tgh expression decreases serum triacylglycerol (TG) and nonesterified fatty acid levels and improves insulin sensitivity. To understand the tissue-specific role of Ces3/TGH in lipid and glucose homeostasis, we generated mice with a liver-specific deletion of Ces3/Tgh expression (L-TGH knockout [KO]). Elimination of hepatic Ces3/Tgh expression dramatically decreased plasma VLDL TG and VLDL cholesterol concentrations but only moderately increased liver TG levels in mice fed a standard chow diet. Significantly reduced plasma TG and cholesterol without hepatic steatosis were also observed in L-TGH KO mice challenged with a high-fat, high-cholesterol diet. L-TGH KO mice presented with increased plasma ketone bodies and hepatic fatty acid oxidation. Intrahepatic TG in L-TGH KO mice was stored in significantly smaller lipid droplets. Augmented hepatic TG levels in chow-fed L-TGH KO mice did not affect glucose tolerance or glucose production from hepatocytes, but impaired insulin tolerance was observed in female mice. Our data suggest that ablation of hepatic Ces3/Tgh expression decreases plasma lipid levels without causing severe hepatic steatosis.

The GTPase ARFRP1 controls the lipidation of chylomicrons in the Golgi of the intestinal epithelium

The uptake and processing of dietary lipids by the small intestine is a multistep process that involves several steps including vesicular and protein transport. The GTPase ADP-ribosylation factor-related protein 1 (ARFRP1) controls the ARF-like 1 (ARL1)-mediated Golgi recruitment of GRIP domain proteins which in turn bind several Rab-GTPases. Here, we describe the essential role of ARFRP1 and its interaction with Rab2 in the assembly and lipidation of chylomicrons in the intestinal epithelium. Mice lacking Arfrp1 specifically in the intestine (Arfrp1vil−/−) exhibit an early post-natal growth retardation with reduced plasma triacylglycerol and free fatty acid concentrations. Arfrp1vil−/− enterocytes as well as Arfrp1 mRNA depleted Caco-2 cells absorbed fatty acids normally but secreted chylomicrons with a markedly reduced triacylglycerol content. In addition, the release of apolipoprotein A-I (ApoA-I) was dramatically decreased, and ApoA-I accumulated in the Arfrp1vil−/− epithelium, where it predominantly co-localized with Rab2. The release of chylomicrons from Caco-2 was markedly reduced after the suppression of Rab2, ARL1 and Golgin-245. Thus, the GTPase ARFRP1 and its downstream proteins are required for the lipidation of chylo­microns and the assembly of ApoA-I to these particles in the Golgi of intestinal epithelial cells.

The effect of acute oral amino acid intake on fatty acid oxidation

We have previously reported a reduced plasma triacylglycerol (TAG) concentration in elderly individuals following chronic intake of amino acids (AAs). To test whether acute intake of AAs increases fatty acid oxidation we compared 13CO2 breath enrichment from 5 elderly hypertriacylglycerolaemic volunteers (mean ± standard deviation (SD): age 66.0 ± 2.9 years; height 1.66 ± 0.04 m; body mass 85.5 ± 19.3 kg; BMI 28.8 ± 6.0 kg·m−2; fasting TAG 192 ± 46 mg·dl−1) during a basal period and a period of acute AA intake, whilst the participants were undergoing a constant infusion of U‐13C16‐palmitate. Participants received a drink containing 1 g of AAs every 10 minutes during the AA period, with 4 breath samples collected, 10 minutes apart, from 1 h 55 min to 2 h 25 min during each period. 13CO2/12CO2 ratio was determined using isotope ratio mass spectrometry. 13C breath enrichment was found to be significantly higher during the AA intake period than during the basal period (mean ± SD: atom % excess 0.22 ± 0.02 vs. 0.09 ± 0.01; P &lt; 0.001). We conclude that acute amino acid intake increases fatty acid oxidation and may constitute a mechanism that contributes to lowering of the plasma TAG concentration. The study is sponsored by 1R01 AG033761 NIH/NIA. Screenings and study visits are being undertaken within the ITS‐Clinical Research Center at UTMB, Galveston, which is funded by grant 1 U54RR026141 from NIH/NCRR.

Lack of acyl-CoA:diacylglycerol acyltransferase 1 reduces intestinal cholesterol absorption and attenuates atherosclerosis in apolipoprotein E knockout mice

Triacylglycerols (TG) are the major storage molecules of metabolic energy and fatty acids in several tissues. The final step in TG biosynthesis is catalyzed by acyl-CoA:diacylglycerol acyltransferase (DGAT) enzymes. Lack of whole body DGAT1 is associated with reduced lipid-induced inflammation. Since one major component of atherosclerosis is chronic inflammation we hypothesized that DGAT1 deficiency might ameliorate atherosclerotic lesion development. We therefore crossbred Apolipoprotein E-deficient (ApoE−/−) mice with Dgat1−/− mice. ApoE−/− and ApoE−/−Dgat1−/− mice were fed Western-type diet (WTD) for 9weeks and thereafter examined for plaque formation. The mean atherosclerotic lesion area was substantially reduced in ApoE−/−Dgat1−/− compared with ApoE−/− mice in en face and aortic valve section analyses. The reduced lesion size was associated with decreased cholesterol uptake and absorption by the intestine, reduced plasma TG and cholesterol concentrations and increased cholesterol efflux from macrophages. The expression of adhesion molecules was reduced in aortas of ApoE−/−Dgat1−/− mice, which might be the reason for less migration capacities of monocytes and macrophages and the observed decreased amount of macrophages within the plaques. From our results we conclude that the lack of DGAT1 is atheroprotective, implicating an additional application of DGAT1 inhibitors with regard to maintaining cholesterol homeostasis and attenuating atherosclerosis.

Effects of protamine hydrochloride from chum salmon milt on lipid metabolism in rats

Protamine is a basic protein whose sulfate is used in medical applications as a carrier for injectable insulin and as a heparin antagonist, while its hydrochloride is used as an antibacterial ingredient for some food products. We previously showed that protamine hydrochloride derived from chum salmon milt inhibited pancreatic lipase and reduced plasma triacylglycerol levels in an oral fat tolerance test in humans. The present study evaluated the effect of chum protamine hydrochloride on lipid metabolism in rats. The single oral administration of protamine hydrochloride (500 mg/kg) reduced plasma triacylglycerol levels in a corn oil tolerance test, and repeated oral administration at a dose of 0, 150, 500, or 1,500 mg/kg with a high fat diet for 7 weeks significantly reduced body weight gain, liver weight, and epididymal adipose tissue, whereas total calorie intakes were not significantly different. These findings could be caused by the suppression of lipid digestibility leading to a significant increase in fecal lipid excretion due to the fact that protamine hydrochloride could bind with bile acids to make a complex that is difficult to digest. Protamine hydrochloride, with a considerable history as food, can be considered to be promising as an anti-obesity functional food material.