Low Density Lipoprotein Triacylglycerol Research Articles

Isotope Labeling and Biochemical Assessment of Liver-Triacylglycerol in Patients with Different Levels of Histologically-Graded Liver Disease

BackgroundNonalcoholic fatty liver disease (NAFLD) prevalence is rapidly growing, and fatty liver has been found in a quarter of the US population. Increased liver lipids, particularly those derived from the pathway of de novo lipogenesis (DNL), have been identified as a hallmark feature in individuals with high liver fat. This has led to much activity in basic science and drug development in this area. No studies to date have investigated the contribution of DNL across a spectrum of disease, although it is clear that inhibition of DNL has been shown to reduce liver fat. ObjectivesThe purpose of this study was to determine whether liver lipid synthesis increases across the continuum of liver injury. MethodsIndividuals (n = 49) consumed deuterated water for 10 d before their scheduled bariatric surgeries to label DNL; blood and liver tissue samples were obtained on the day of the surgery. Liver lipid concentrations were quantitated, and levels of protein and gene expression assessed. ResultsIncreased liver DNL, measured isotopically, was significantly associated with liver fatty acid synthase protein content (R = 0.470, P = 0.003), total steatosis assessed by histology (R = 0.526, P = 0.0008), and the fraction of DNL fatty acids in plasma very low-density lipoprotein-triacylglycerol (R = 0.747, P < 0.001). Regression analysis revealed a parabolic relationship between fractional liver DNL (percent) and NAFLD activity score (R = 0.538, P = 0.0004). ConclusionThese data demonstrate that higher DNL is associated with early to mid stages of liver disease, and this pathway may be an effective target for the treatment of NAFLD and nonalcoholic steatohepatitis.This study was registered at clinicaltrials.gov as NCT03683589.

Sex and Depot Differences in Palmitoleic Acid Content of Human Blood and Fat.

Palmitoleic acid has been classified as an insulin-sensitizing lipokine, but evidence for this from human studies has been inconsistent. We hypothesized that this is related to either the types of samples or conditions under which samples are collected. We measured plasma palmitoleic acid and total free fatty acids (FFA) using ultra-performance liquid chromatography in blood samples collected from 34 adults under a variety of conditions. We collected duplicate samples of adipose (n = 10), FFA (n = 9), and very low density lipoprotein triacylglycerol (VLDL-TAG) (n = 7) to measure the palmitoleic acid as a percentage of total fatty acids. We tested whether the percentage of palmitoleic acid was correlated with insulin resistance, as measured by homeostatic model of insulin resistance (HOMA-IR). Adipose stearoyl-coenzyme A desaturase 1 (SCD-1) protein was measured by capillary Western blotting. FFA-palmitoleic acid percentage increased as a function of total FFA and was greater (p < 0.005) in females than males. Adipose palmitoleic acid percentage was greater in females than males (p < 0.001), as was adipose SCD-1. Palmitoleic acid was greater in femoral fat than in abdominal fat in both females and males (p < 0.001), and correlated positively with HOMA-IR only in females. The test-retest reliability values for percentage palmitoleic acid were 7 ± 10% for adipose, 24 ± 26% for VLDL, and 53 ± 31% for FFA. Because FFA-palmitoleic acid percentage varies as a function of total FFA, investigators should re-evaluate how palmitoleic acid data is presented. The positive relationship between adipose palmitoleic acid and HOMA-IR in females suggests that it is not a potent insulin-sensitizing lipokine in humans.

Lipid Profile of Streptozotocin-Induced Diabetic Wistar Albino Rats Treated with Aqueous Extracts of Nauclea latifolia

In recent times there has been a steady increase in researches aimed at searching for plant agents that can be used in the management of diabetes mellitus and its complications with minimal side effects compared with the anti-diabetic drugs in the pharmaceutical market. This work is on the effect of aqueous extracts ofNauclea latifolia plant on serum lipid profile in streptozotocin- induced diabetic rats. Thirty mature male Wistar albino rats were divided into six treatment groups of five rats each. Group A was normal control and group B was streptozotocin-induced diabetic control. Groups C, D and E were streptozotocin- induced diabetic rats treated daily with 500mg / kg. body weight of aqueous extracts of stem-bark, leaves and root-bark of Nauclea latifolia respectively. Group F was streptozotocin- induced diabetic rats treated daily with 5mg / kg. body weight of glibenclamide and the treatment was for 28 days. The serum total cholesterol, high density lipoprotein cholesterol and triacylglycerol of the rats were determined using assay kits from Agape Diagnostic, Switzerland while very low density lipoprotein cholesterol was determined by calculation according to the method of Burstein and Samaile (1960). The low density lipoprotein cholesterol was estimated using the method of Friedwald, Levy and Fredrickson (1972) which entails differential subtraction of the sum of the cholesterol fractions from the total cholesterol. The parameters were analyzed using One- way Analysis of Variance with the level of significance determined by least significant difference. The streptozotocin-induced diabetic control rats had their serum levels of total cholesterol, low density lipoprotein cholesterol, very low density lipoprotein cholesterol and triacylglycerol significantly elevated compared with the normal control. Nauclea latifolia aqueous extracts brought about significant reduction of total cholesterol, low density lipoprotein cholesterol and triacylglycerol levels in the diabetic treated rats. The outcome of this work indicates that Nauclea latifolia aqueous extracts have ameliorating effect on diabetic complications due to high serum lipid profile levels.

Lipid Profile of Streptozotocin-Induced Diabetic Wistar Albino Rats Treated with Aqueous Extracts of Nauclea latifolia

In recent times there has been a steady increase in researches aimed at searching for plant agents that can be used in the management of diabetes mellitus and its complications with minimal side effects compared with the anti-diabetic drugs in the pharmaceutical market. This work is on the effect of aqueous extracts ofNauclea latifolia plant on serum lipid profile in streptozotocin- induced diabetic rats. Thirty mature male Wistar albino rats were divided into six treatment groups of five rats each. Group A was normal control and group B was streptozotocin-induced diabetic control. Groups C, D and E were streptozotocin- induced diabetic rats treated daily with 500mg / kg. body weight of aqueous extracts of stem-bark, leaves and root-bark of Nauclea latifolia respectively. Group F was streptozotocin- induced diabetic rats treated daily with 5mg / kg. body weight of glibenclamide and the treatment was for 28 days. The serum total cholesterol, high density lipoprotein cholesterol and triacylglycerol of the rats were determined using assay kits from Agape Diagnostic, Switzerland while very low density lipoprotein cholesterol was determined by calculation according to the method of Burstein and Samaile (1960). The low density lipoprotein cholesterol was estimated using the method of Friedwald, Levy and Fredrickson (1972) which entails differential subtraction of the sum of the cholesterol fractions from the total cholesterol. The parameters were analyzed using One- way Analysis of Variance with the level of significance determined by least significant difference. The streptozotocin-induced diabetic control rats had their serum levels of total cholesterol, low density lipoprotein cholesterol, very low density lipoprotein cholesterol and triacylglycerol significantly elevated compared with the normal control. Nauclea latifolia aqueous extracts brought about significant reduction of total cholesterol, low density lipoprotein cholesterol and triacylglycerol levels in the diabetic treated rats. The outcome of this work indicates that Nauclea latifolia aqueous extracts have ameliorating effect on diabetic complications due to high serum lipid profile levels.

Therapeutic effect of co-administered salvianolate and atorvastatin calcium on coronary heart disease patients with angina pectoris, and their blood lipid levels

Purpose: To investigate the clinical effect of combination of salvianolate and atorvastatin on blood lipids of coronary heart disease patients with angina pectoris (CHD-AP).Method: Patients with CHD-AP (n = 104) from January 2016 to January 2017 were randomly assigned to two groups: control group treated with atorvastatin (10 mg/day), and study group was administered atorvastatin (10 mg/day, oral) plus salvianolate (200 mg/day in 5 % glucose, iv). Palpitation, chest distress, improvement in myocardial ischemia, myocardial function, and hemodynamics were determined and used to assess treatment effectiveness in the two groups. Differences in blood lipid profiles were also investigated.Results: Improvement in palpitation, chest distress, myocardial ischemia and myocardial function in the study group were significantly higher than in the control group (p < 0.05). In the study group, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and triacylglycerols (TGs) significantly decreased, relative to the control group (p < 0.05).Conclusion: Treatment of CHD-AP patients with combination of salvianolate and atorvastatin significantly ameliorates coronary heart disease and angina pectoris, and also reduces their blood lipid levels.Keywords: Salvianolate, Atorvastatin, Coronary heart disease, Angina pectoris, Blood lipids

Reduction in Secretion of Very Low Density Lipoprotein-Triacylglycerol by a Matrix Metalloproteinase Inhibitor in a Rat Model of Diet-Induced Hypertriglyceridemia.

Matrix metalloproteinase inhibitors (MMPIs) reduced serum triacylglycerol (TAG) levels in streptozotocin-induced diabetic rats and Zucker fa/fa rats in our previous study. However, the mechanisms underlying TAG reduction by MMPIs remain unclear. The present study aimed to elucidate the mechanism by which F81-1144b, an MMPI, lowers serum TAG levels in an animal model of high-sucrose diet (HSD)-induced hypertriglyceridemia. F81-1144b was repeatedly administered to rats fed HSD, and its effects were evaluated on TAG levels in serum and the liver, very low density lipoprotein (VLDL) secretion, de novo fatty acid (FA) synthesis in the liver, and the expression of genes regulating the metabolism of FA, TAG, and VLDL in the liver and serum. F81-1144b lowered TAG levels in serum and the liver, VLDL-TAG secretion, de novo FA synthesis in the liver, and serum levels of insulin and glucose. F81-1144b suppressed the expression of genes related to the de novo synthesis of FA and TAG, key proteins (lipin 1 and apolipoprotein CIII) responsible for VLDL metabolism, and sterol regulatory element-binding protein-1c and carbohydrate response element-binding protein. F81-1144b little affected the expression of genes related directly to the degradation of TAG or FA, but it upregulated that of gene for uncoupling protein 2 in the liver. These results suggest that MMPIs are a novel type of therapeutic agent for the treatment of hypertriglyceridemia, because the metabolic effects of F81-1144b expected from changes in the expression of genes regulating lipid metabolism would alter metabolism differently from those induced by fibrates, niacin, or n-3 FAs.

The Lipid Lowering and Cardioprotective Effects of Vernonia calvoana Ethanol Extract in Acetaminophen-Treated Rats.

Background: Paracetamol overdose/abuse as a result of self-medication is a common occurrence amongst people living in low/middle income countries. The present study was designed to investigate the hypolipidemic and cardioprotective potentials of Vernonia calvoana (VC) ethanol extract in acetaminophen (paracetamol)-treated rats. Methods: Thirty-five Wistar rats weighing 100–150 g were randomly assigned into five groups of seven rats each. Groups 2–5 received high doses of paracetamol to induce liver damage, while group 1 was used as normal control. Afterwards, they were allowed to receive varying doses of VC (group 3 and 4) or vitamin E (group 5), whilst groups 1 and 2 were left untreated. The treatment period lasted for twenty one days after which sera were harvested and assayed for serum lipid indices using standard methods. Results: Groups 3 to 5 treated animals indicated significant decrease (p < 0.001) in low density lipoprotein cholesterol (LDL-c), total cholesterol (TC) and triacylglycerol (TG) levels relative to the normal and acetaminophen-treated controls, the atherogenic index showed a significant decrease (p < 0.001) in all treated groups compared with normal and acetaminophen-treated controls. However, the VC- and vitamin E-treated groups showed significant (p < 0.001) increase in high density lipoprotein cholesterol (HDL-c) relative to the controls. Conclusions: Data from our study suggest that ethanol leaf extract of VC possesses probable hypolipidemic and cardioprotective effects.

A Comparative Analysis of Lipid Profile among Rural and Urban School Going Male Adolescents in Katsina State, Nigeria

Aim: The study is aimed at analyzing blood samples from 484 male school going adolescents; of which 263 were randomly selected from a public school in Katsina metropolis (urban setting) and 221 from a public school in Batsari (rural setting) for the levels of serum total cholesterol (TC), high density lipoprotein cholesterol (HDL - CH), low density lipoprotein cholesterol (LDL - CH) and triacyl glycerol (TG) in order to ascertain a risk of cardiovascular disease ( CVD). Study Design: A cross sectional study was conducted among male adolescents from urban and rural settings aged between 12 - 18 years attending public secondary schools in Katsina State Nigeria to assess their nutritional status.

Gene Transfer of Apolipoprotein A-V Improves the Hypertriglyceridemic Phenotype of apoa5 (−/−) mice

Apolipoprotein (apo) A-V is a low abundance protein with a profound influence on plasma triacylglycerol levels. In human populations, single nucleotide polymorphisms and mutations in APOA5 positively correlate with hypertriglyceridemia. As an approach to preventing the deleterious effects of chronic hypertriglyceridemia, apoA-V gene therapy has been pursued. Recombinant adeno-associated virus (AAV) 2/8 harboring the coding sequence for human apoA-V or a control AAV2/8 was transduced into hypertriglyceridemic apoa5 (-/-) mice. After injection of 1×10(12) viral genome AAV2/8-apoA-V, maximal plasma levels of apoA-V protein were achieved at 3 to 4 weeks, after which the concentration slowly declined. Complementing the appearance of apoA-V was a decrease (50±6%) in plasma triacylglycerol content compared with apoa5 (-/-) mice treated with AAV2/8-β-galactosidase. After 8 weeks the mice were euthanized and plasma lipoproteins separated. AAV2/8-apoA-V-transduced mice displayed a dramatic reduction in very low-density lipoprotein triacylglycerol content. Vector generated apoA-V in plasma associated with both very low-density lipoprotein and high-density lipoprotein fractions. Taken together, the data show that gene transfer of apoA-V improves the severe hypertriglyceridemia phenotype of apoa5 (-/-) mice. Given the prevalence of hypertriglyceridemia, apoA-V gene therapy offers a potential strategy for maintenance of plasma triacylglycerol homeostasis.

Sucrose-rich feeding during rat pregnancy-lactation and/or after weaning alters glucose and lipid metabolism in adult offspring

1. Adverse fetal and early life environments predispose to the development of metabolic disorders in adulthood. The present study examined whether offspring of normal Wistar dams fed a high-sucrose diet (SRD) developed impaired lipid and glucose homeostasis when fed a control diet (CD) after weaning. In addition, we investigated whether there were more pronounced derangements in lipid and glucose homeostasis when offspring of SRD-fed Wistar were fed an SRD after weaning compared with those in offspring of CD-fed dams weaned on an SRD. 2. During pregnancy and lactation, female rats were fed either an SRD or CD. After weaning, half the male offspring from both groups were fed a CD or SRD, up to 100 days of age (CD-CD, CD-SRD, SRD-SRD and SRD-CD groups). 3. Final bodyweight was similar between all groups, although offspring of SRD-fed dams had lighter bodyweight at birth. Plasma lipid and glucose levels were significantly higher (P < 0.05) without changes in insulin levels in the CD-SRD, SRD-SRD and SRD-CD groups compared with the CD-CD group. Dyslipidaemia in the CD-SRD and SRD-SRD groups resulted from increased secretion of very low-density lipoprotein triacylglycerol, as well as decreased triacylglycerol (TAG) clearance that was associated with increased liver TAG content (P < 0.05) compared with the CD-CD group. The hypertriglyceridaemia observed in the SRD-CD group was mostly associated with decreased TAG clearance. Altered glucose and insulin tolerance were observed when the SRD was fed during any period of life. 4. These data support the hypothesis that early life exposure to SRD is associated with changes in lipid and glucose metabolism, leading to an unfavourable profile in adulthood, regardless of whether offspring consumed an SRD after weaning.

Effects of dietary inulin, statin, and their co-treatment on hyperlipidemia, hepatic steatosis and changes in drug-metabolizing enzymes in rats fed a high-fat and high-sucrose diet

BackgroundRats fed a high-fat and high-sucrose (HF) diet develop hepatic steatosis and hyperlipidemia. There are several reports that a change in nutritional status affects hepatic levels of drug-metabolizing enzymes. Synthetic inulin is a dietary component that completely evades glucide digestion. Supplementing a HF diet with inulin ameliorates hypertriglycemia and hepatic steatosis, but not hypercholesterolemia. This study aimed at distinguishing the effects of synthetic inulin and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin), which inhibit cholesterol biosynthesis.MethodsWe examined effects of co-treatment with synthetic inulin (5%) and fluvastatin (0, 4, and 8 mg/kg, per os) on body weight, epidydimal white adipose tissue weight, serum and hepatic lipid profiles, and hepatic cytochrome P450 (CYP) mRNA and protein profiles in rats fed a standard diet or a HF diet for 3 weeks.ResultsTreatment with the synthetic inulin (5%) or fluvastatin at 4 mg/kg (lethal dose in rats fed the HF diet, 8 mg/kg) ameliorated the elevation in hepatic triacylglycerol and total cholesterol levels in rats fed the HF diet. Whereas co-treatment with the inulin (5%) and fluvastatin (4 mg/kg) had a tendency to more strongly suppress the elevation in serum levels of very low density lipoprotein triacylglycerol than either treatment alone, no additive or synergistic effect was found in decrease in hepatic lipid levels. Hepatic levels of CYP1A1/2 and CYP2E1 mRNA and protein and methoxyresorufin O-demethylase and ethoxyresorufin O-deethylase activities were reduced in rats fed the HF diet. The synthetic inulin alleviated the reduction in hepatic levels of CYP1A1/2 and CYP2E1 mRNA and protein more strongly than fluvastatin, and no synergistic effects were observed on co-treatment. Furthermore, hepatic levels of aryl hydrocarbon receptor mRNA were decreased in rats fed the HF diet and recovered to near normal values with the intake of dietary inulin, which correlated with change in CYP1A1/2.ConclusionsDietary inulin alone was effective to prevent the development of hepatic steatosis, ameliorate nutritional effects, and alleviate the hepatic change in the expression of CYP1A1/2 and CYP2E1, while co-treatment with statin did not have additive or synergistic effects and statin may cause adverse effects in rats fed the HF diet.

Metabolic balancing acts of vitamin A in type-2 diabetes and obesity

Using mice that lack retinaldehyde dehydrogenase 1 gene (Raldh1-/- mice), Kierfer et al demonstrated that retinoids (metabolites of Vitamin A) play an important role in the regulation of cellular metabolisms and energetics. The Aldh1a1-/- mice were leaner and less prone to accumulate subcutaneous and visceral fat, and to acquire insulin resistance on high fat diet. Their lower fasting glucose levels concomitant with reduced hepatic expression of glucose 6-phosphatase and phosphoenol pyruvate carboxy kinase genes indicated that Aldh1a1-/- mice were defective in gluconeogenesis. These mice also had lower plasma levels of triglycerides, very low-density lipoprotein and low-density lipoprotein-triacylglycerol, while their skeletal muscles elicited higher expression of carnitine palmatoyl transferase, medium chain acyl-A dehydrogenase, peroxisome proliferation activated receptor (PPARα and PPARδ. Thus, the improved lipid and lipoprotein profiles of Raldh1a1-/- mice resulted from a combination of reduced lipogenesis and enhanced fatty acid oxidation by retinoids. The mechanistic details of how retinoids integrate fasting glucose, hepatic gluconeogenesis and adaptive thermogenesis independent of body mass deserve further study.

Effect of germinated &amp;lt;i&amp;gt;Glycine max&amp;lt;/i&amp;gt; seeds on glycemic control in STZ+NAD induced type 2 diabetic models: a preliminary study

Objective: Glycine max (soybean) is a legume (Fabaceae) native to East Asia. Glycine max seeds are a powerful stimulant of immune system, used to decrease menopause symptoms, estrogen, treat certain types of cancers including that of the breast, lungs, prostate. It is also used for treating diabetes, liver and kidney disorders. The study aimed to investigate the effect of germinated Glycine max seeds on glycemic control in Streptozotocin (STZ) plus Nicotinamide (NAD) induced type 2 diabetic rats. Methods: The effect of Glycine max seed extract at the dose of 100, 200, 400 mg/kg b.w, respectively, germinated at different time intervals was investigated in STZ+NAD induced diabetic rats. The study was conducted for 21 days to investigate the effect of extract on blood biochemical parameters indicative of hyperglycemia; fasting blood glucose (FBG), oral glucose tolerance test (OGTT), glycosylated hemoglobin (GHb) and lipid profile, i.e. total cholesterol (TC), low and high density lipoprotein cholesterol (LDL-c and HDL-c) and triacylglycerol (triglycerides, TG) levels. Results: Aqueous extract (200 mg/kg b.w) of 12 h soaked and germinated Glycine max seeds produced significant reduction in FBG after 90 min (9.6%) and 3 h (15.6%) of administration. When the extract (200 mg/kg) was administered daily for three weeks to diabetic rats, significant fall in FBG (48.6%) and GHb (30.2%) was observed. Glucose tolerance was also found to be improved. Extract also showed significant hypolipidemic effect in diabetic rats as apparent from fall in TG, TC and LDL-c, and significant improvement on HDL-c. Conclusion: The results suggest that aqueous extract of 12 h germinated Glycine max seeds possess antihyperglycemic as well as hypolipidemic activity.

Apolipoprotein B and triacylglycerol secretion in human triacylglycerol hydrolase transgenic mice

Apolipoprotein B (apoB)-containing lipoproteins play a critical role in whole body lipid homeostasis and the pathogenesis of atherosclerosis. The assembly of hepatic apoB-containing lipoproteins, VLDL, is governed by the availability of lipids, including triacylglycerol (TG). The majority of TG associated with VLDL is derived from the hepatic cytoplasmic lipid stores by a process involving lipolysis followed by reesterification. Microsomal triacylglycerol hydrolase (TGH) has been demonstrated to play a role in the lipolysis/reesterification process. To evaluate the potential regulatory role of TGH in hepatic VLDL assembly, we developed inducible transgenic mice expressing a human TGH minigene under the control of the mouse metallothionein promoter. Induction of human TGH by zinc resulted in liver-specific expression of the enzyme associated with 3- to 4-fold increases in lipolytic activity that could be attenuated with a TGH-specific inhibitor. Augmented TGH activity led to increased secretion of newly synthesized apoB and plasma TG levels. These results suggest that increased hepatic expression of TGH leads to a more proatherogenic plasma lipid and apoB profile.

A zinc finger HIT domain-containing protein, ZNHIT-1, interacts with orphan nuclear hormone receptor Rev-erbβ and removes Rev-erbβ-induced inhibition of apoCIII transcription

The orphan receptors, Rev-erbalpha and Rev-erbbeta, are members of the nuclear receptor superfamily and specifically repress apolipoprotein CIII (apoCIII) gene expression in rats and humans. Moreover, Rev-erbalpha null mutant mice have elevated very low density lipoprotein triacylglycerol and apoCIII levels. However, ligands for Rev-erb are unknown and the regulatory mechanism of Rev-erb is poorly understood. Conceivably, cofactors for Rev-erb may play an important role in the regulation of lipid metabolism. In this study, a zinc finger HIT domain-containing protein, ZNHIT-1, interacted with Rev-erbbeta. ZNHIT-1 was found to be a conserved protein in eukaryotes and was highly abundant in human liver. Furthermore, ZNHIT-1 was identified as a nuclear protein. Serial truncated fragments and substitution mutations established a putative nuclear localization signal at amino acids 38-47 of ZNHIT-1. A putative ligand-binding domain of Rev-erbbeta and the FxxLL motif of ZNHIT-1 were required for their interaction. Finally, ZNHIT-1 was recruited by Rev-erbbeta to the apoCIII promoter and removed the Rev-erbbeta-induced inhibition of apoCIII transcription. These findings demonstrate that ZNHIT-1 functions as a cofactor to regulate the activity of Rev-erbbeta, and may play a role in lipid metabolism.

A single bout of brisk walking increases basal very low-density lipoprotein triacylglycerol clearance in young men

Very low-density lipoprotein triacylglycerol (VLDL-TG) turnover rate was evaluated in the morning, 12 hours after a single bout of brisk walking (90 minutes at approximately 60% of V̇ o 2max; EXE), compared to a resting control period (CON) in 10 recreationally active men. VLDL-TG fractional catabolic rate was calculated from the decay in isotopic enrichment after a bolus injection of [ 2H 5]glycerol. Plasma VLDL-TG concentration was 24% lower in the morning after the EXE trial compared to control (0.47 ± 0.04 and 0.36 ± 0.04 mmol L −1, for CON and EXE, respectively; P < .01). Serum insulin (7.4 ± 0.7 and 5.6 ± 0.4 mIU L −1, CON and EXE, respectively; P < .05) and plasma glucose (5.6 ± 0.1 and 5.4 ± 0.1 mmol/L, CON and EXE, respectively; P < .05) concentrations were also significantly lower in the EXE trial. Insulin sensitivity (homeostasis model assessment [HOMA] index) was improved by 27% in EXE compared with the CON trial ( P < .05).VLDL–apolipoprotein B-100 and plasma fatty acid concentrations were similar in the two trials. Hepatic VLDL-TG secretion rates were not significantly affected by exercise (13.1 ± 1.2 and 13.2 ± 1.6 μmol .min −1 for the CON and EXE trials, respectively), whereas VLDL-TG clearance rate increased by 36% (28.1 ± 1.3 and 38.1 ± 3.5 mL .min −1 for the CON and EXE trials, respectively; P < .05). It is concluded that the decrease in fasting plasma VLDL-TG concentration observed 12 hours after brisk walking is related mainly to increased VLDL-TG clearance from plasma.

The reduction of dietary sucrose improves dyslipidemia, adiposity, and insulin secretion in an insulin-resistant rat model

Objective The purpose of the present work was to investigate whether changes in the type of carbohydrate in the diet are able to improve and/or reverse hyperlipemia, impaired glucose homeostasis, and insulin secretion from β-cells induced in rats by chronically feeding a high sucrose intake. Methods For 30 wk male Wistar rats received a sucrose-rich diet (63% w/w) or a control diet in which sucrose was replaced by starch. After this period, the sucrose-fed animals were randomly divided into two groups: the first group continued with this diet up to 42 wk and the other received the same diet but with a 20% reduction in the amount of sucrose and the rest of the carbohydrate being replaced by starch. Rats were fed with this diet for the next 12 wk. Results The reduction of the amount of sucrose in the diet showed a substantial improvement ( P < 0.05) of dyslipidemia associated with an amelioration of “in vivo” very low-density lipoprotein-triacylglycerol secretion and triacylglycerol removal rate from the circulation. Glucose homeostasis and glucose-induced insulin release from β-cells were improved ( P < 0.05), although these values did not reach those observed in rats fed a control diet. Visceral adiposity was also significantly reduced ( P < 0.05). Conclusion These data are consistent with the suggestion that the composition of the diet could contribute to improvements in dyslipidemia, insulin resistance, and adiposity by direct effects on the lipid metabolism and insulin action and indirectly through the reduction of visceral fat mass and distribution.

Effect of Hydroxycut Intake on Fasted and Postprandial Lipemia in Rats

Hydroxycut, an herbal supplement not currently defined as a drug, is frequently sold over the counter to increase exercise performance, build muscles, and burn fat. The effects of 8 wk of hydroxycut-induced changes on blood lipid profile in rats fed with either regular or high-fat diet were evaluated. Regardless of fat content in the diet, the doses of hydroxycut used significantly decreased fasting serum concentrations of cholesterol, triacylglycerol (TAG), low-density lipoprotein (LDL) cholesterol, total apolipoprotein B (apo B), and LDL/high-density lipoprotein (HDL) cholesterol ratio. A significant increase in serum blood glucose level was observed with hydroxycut intake in the presence of a high-fat diet. No hydroxycut-related changes in serum activities of serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate dehydrogenase (SGPT), lactate dehydrogenase (LDH), and creatinine phosphokinase (CPK) enzymes were noted, indicating no liver damage occurred. A decrease in liver fat content was observed with hydroxycut intake. The drug did not affect the number and composition of secreted very-low-density lipoprotein (VLDL) particles except for a decrease in VLDL TAG when the fat content in the diet was high. Hydroxycut reduced significantly LDL apo B and LDL TAG and cholesterol concentrations. Hydroxycut increased TAG and cholesterol excretion in feces. A single intragastric food load containing hydroxycut reduced significantly postprandial plasma TAG concentration in a dose-dependent manner. In conclusion, hydroxycut intake in recommended doses exerts a beneficial impact on atherosclerosis, an effect attributed to improved clearance and metabolism of lipoprotein particles, and to a lesser extent to an increased excretion of TAG and cholesterol in the feces. More studies are needed to ensure the safety of long-term use of hydroxycut.

Mutation of F417 but not of L418 or L420 in the lipid binding domain decreases the activity of triacylglycerol hydrolase

Human triacylglycerol hydrolase (hTGH) has been shown to play a role in hepatic lipid metabolism. Triacylglycerol hydrolase (TGH) hydrolyzes insoluble carboxylic esters at lipid/water interfaces, although the mechanism by which the enzyme adsorbs to lipid droplets is unclear. Three-dimensional modeling of hTGH predicts that catalytic residues are adjacent to an alpha-helix that may mediate TGH/lipid interaction. The helix contains a putative neutral lipid binding domain consisting of the octapeptide FLDLIADV (amino acid residues 417-424) with the consensus sequence FLXLXXXn (where n is a nonpolar residue and X is any amino acid except proline) identified in several other proteins that bind or metabolize neutral lipids. Deletion of this alpha-helix abolished the lipolytic activity of hTGH. Replacement of F417 with alanine reduced activity by 40% toward both insoluble and soluble esters, whereas replacement of L418 and L420 with alanine did not. Another potential mechanism of increasing TGH affinity for lipid is via reversible acylation. Molecular modeling predicts that C390 is available for covalent acylation. However, neither chemical modification of C390 nor mutation to alanine affected activity. Our findings indicate that F417 but not L418, L420, or C390 participates in substrate hydrolysis by hTGH.

Contributions of Different Fatty Acid Sources to Very Low-Density Lipoprotein-Triacylglycerol in the Fasted and Fed States

The liver's regulation of fatty acids (FAs) postprandially may contribute to risk of metabolic diseases. Measurements of steady-state metabolism were used to investigate sources of FAs used for very low-density lipoprotein (VLDL)-triacylglycerol (TG) synthesis during fasting and feeding in vivo. Subjects were duodenally fed a formula labeled with the stable isotope glyceryl tri-palmitate-d(31) and iv infused with [1,2,3,4-(13)C(4)]-palmitatic acid and [1-(13)C(1)]-acetate to quantitate the liver's use of FAs originating from adipose tissue and de novo lipogenesis. This study of healthy men (n = 12; body mass index, 24.4 +/- 2.7 kg/m(2)) was conducted at a General Clinical Research Center. Concentrations of metabolites during fasting and feeding, sources of FAs used for lipoprotein synthesis, rate of appearance of serum nonesterified FA (NEFA), and VLDL-TG were measured. During fasting, 77.2 +/- 14.0% of VLDL-TG was derived from adipose FA recycling and 4.0 +/- 3.6% from lipogenesis; with feeding, 43.6 +/- 18.6% came from adipose FAs (P < 0.001), 8.2 +/- 5.1% from lipogenesis (P < 0.001), 15.2 +/- 13.7% from uptake of chylomicron-remnant TG, and 10.3 +/- 6.9% from dietary FA spillover into the serum NEFA pool. Fed-state VLDL-TG from NEFA reesterification decreased in proportion to the reduction in adipose NEFA appearance. These data: 1) quantify the extent to which the healthy liver manages its use of different sources of FAs that flow to it, 2) demonstrate how the postprandial reduction in adipose-NEFA flux may be partially replaced by other sources, and 3) highlight the potential for dietary FA spillover to support the continued dominance of NEFA as a substrate for VLDL-TG synthesis.