Effects of short-term overfeeding with fructose,fat and fructose plus fat on plasma and hepatic lipids in healthy men

AimsThe present study aimed to assess the effects of excess fat, fructose and fat-plus-fructose intakes on intrahepatocellular lipid (IHCL).MethodsHealthy male subjects were studied after an isocaloric diet or a 7-day high-fructose (Fru: +3.5 g fructose/kg fat-free mass/day, +35% energy), high-fat (Fat: +30% energy as saturated-fat) or high-fructose, high-fat diet (FruFat: +3.5 g fructose/kg fat-free mass/day, +30% energy as fat, +65% total energy). IHCL was measured by ¹H magnetic resonance spectroscopy.ResultsAll hypercaloric diets increased IHCL (Fru: +16%; Fat: +86%; FruFat: +133%; P < 0.05). Very low-density lipoprotein (VLDL) triacylglycerols increased after Fru (+58%; P < 0.05), but decreased after Fat (−22%; P < 0.05), while no change was observed after FruFat.ConclusionFat and fructose both increased IHCL, but fructose increased, while fat decreased, VLDL triacylglycerols. However, excess fat and fructose combined had additive effects on IHCL and neutralizing effects on VLDL triglycerides. This suggests that fructose stimulates, while fat inhibits, hepatic VLDL triacylglycerol secretion.     

Impact of hematopoietic cyclooxygenase-1 deficiency on obesity-linked adipose tissue inflammation and metabolic disorders in mice

ObjectiveAdipose tissue (AT)-specific inflammation is considered to mediate the pathological consequences of obesity and macrophages are known to activate inflammatory pathways in obese AT. Because cyclooxygenases play a central role in regulating the inflammatory processes, we sought to determine the role of hematopoietic cyclooxygenase-1 (COX-1) in modulating AT inflammation in obesity.Materials/MethodsBone marrow transplantation was performed to delete COX-1 in hematopoietic cells. Briefly, female wild type (wt) mice were lethally irradiated and injected with bone marrow (BM) cells collected from wild type (COX-1 +/+) or COX-1 knock-out (COX-1 ?/?) donor mice. The mice were fed a high fat diet for 16 weeks.ResultsThe mice that received COX-1 ?/? bone marrow (BM-COX-1 ?/?) exhibited a significant increase in fasting glucose, total cholesterol and triglycerides in the circulation compared to control (BM-COX-1 +/+) mice. Markers of AT-inflammation were increased and were associated with increased leptin and decreased adiponectin in plasma. Hepatic inflammation was reduced with a concomitant reduction in TXB2 levels. The hepatic mRNA expression of genes involved in lipogenesis and lipid transport was increased while expression of genes involved in regulating hepatic glucose output was reduced in BM-COX-1 ?/? mice. Finally, renal inflammation and markers of renal glucose release were increased in BM-COX-1 ?/? mice.ConclusionHematopoietic COX-1 deletion results in impairments in metabolic homeostasis which may be partly due to increased AT inflammation and dysregulated adipokine profile. An increase in renal glucose release and hepatic lipogenesis/lipid transport may also play a role, at least in part, in mediating hyperglycemia and dyslipidemia, respectively.     

Micro RNA-146a expression,NF-κB/P65 activity and serum pentosidine levels as potential biomarkers for disease severity in primary knee osteoarthritis patients

IntroductionIdentifying osteoarthritis (OA) patients at high risk for progression is important.Aim of the workTo study the expression pattern of micro RNA-146a (miR-146a), NF-κB/p65 binding activity and serum pentosidine levels in patients with primary knee OA (KOA) in order to assess their value as potential markers for disease prognosis and severity and to clarify their role in disease pathogenesis.Patient and methodsThis study was conducted on 36 female patients with primary KOA divided radiologically into those with moderate KOA and severe KOA as well as 20 controls. The expression patterns of miR-146a were analyzed using quantitative real time-PCR, NF-κB/p65 binding activity and serum pentosidine levels determined using ELISA kits.ResultsmiR-146a expression levels were significantly higher in KOA patients than controls being significantly higher in moderate KOA compared to severe cases. NF-κB/p65 binding activity and serum pentosidine levels were significantly higher in severe KOA patients (0.74 ± 0.06 and 425.2 ± 40.3 pg/ml) compared to moderate cases (0.3 ± 0.03 and 311.4 ± 30 pg/ml) (p < 0.05) and were higher compared to controls (0.15 ± 0.08 and 257 ± 32.3 pg/ml respectively) (p < 0.05).ConclusionThis study may emphasize the role of miR-146a expression, and NFKB/p65 binding activity in primary KOA. Assessment of NFKB/p65 binding activity, miR-146a expression, and serum pentosidine in primary KOA patients could extend the panel of laboratory tests available to monitor the severity and progress of the disease and might benefit as markers for detection of patients with high risk for disease progression; and hence to be a novel therapeutic target to inhibit cartilage destruction.     

Stress oxydant et effets bénéfiques rénaux de la restriction sodée dans l’insulinorésistance chez le rat

The aim of this work was to evaluate the influence of dietary sodium restriction on metabolic and renal changes associated with insulin resistance. At 8 weeks of age, rats received either a diet containing 60% fructose with or without sodium or a standard diet for 12 weeks. The insulin resistance and albuminuria induced by the high fructose diet were associated with a fibrosis and increase in oxidative stress in the kidney. The low salt diet prevented insulin resistance, renal fibrosis and albuminuria induced by the fructose diet. These beneficial effects on the kidney were associated with a decrease in kidney NADPH oxidase activity. Oxidative status is probably one of the major targets of the favourable effect of salt restriction on renal changes associated with insulin resistance, without excluding the involvement of other mechanisms.     

Effect of Atorvastatin and Ezetimibe Treatment on Serum Lipid Profile and Oxidative State in Rats Fed With a High-Cholesterol Diet

IntroductionThe effects of ezetimibe and atorvastatin on serum lipid profile and oxidant-antioxidant system were investigated in rats.MethodsSeventy-two Sprague-Dawley rats were assigned to 6 groups. Group 1 was fed with standard rat chow. Group 2 and the other 4 groups were fed with a high-cholesterol diet: 10 mg/kg/d atorvastatin to group 3; 1 mg/kg/d atorvastatin to group 4; 10 mg/kg/d atorvastatin and 1 mg/kg/d ezetimibe to group 5; and 1 mg/kg/d ezetimibe to group 6. After 3 months, serum total, low-density lipoprotein, high-density lipoprotein cholesterol, and triglyceride levels, and the activities of malondialdehyde, glutathione peroxidase, and superoxide dismutase were measured in the plasma. In addition, the left anterior descending and femoral arteries were examined histopathologically.ResultsSerum total, low-density lipoprotein cholesterol, and triglyceride levels decreased slightly in group 3. However, administration of 1 mg/kg/d atorvastatin or 1 mg/kg/d ezetimibe did not significantly change lipid parameters. Plasma malondialdehyde levels slightly increased in group 2 compared with controls and decreased compared with both the atorvastatin regimens. However, malondialdehyde levels increased with the addition of ezetimibe to atorvastatin. Only the administration of ezetimibe significantly elevated the levels of malondialdehyde. Glutathione peroxidase and superoxide dismutase levels were also found to be significantly reduced in the groups receiving ezetimibe when compared with atorvastatin groups.ConclusionsAtorvastatin has a beneficial effect on oxidative stress in rats fed with high-cholesterol diet. A combination of ezetimibe with atorvastatin diminishes the beneficial effects of atorvastatin. Conversely, the sole administration of ezetimibe increases oxidative stress.     

A new approach to facilitate diagnosis of nonalcoholic fatty liver disease through a galactose single point method in rats with fatty liver

BackgroundLiver biopsy reliably diagnoses nonalcoholic fatty liver disease, but its invasiveness and inter- and intra-observer errors limit its usefulness in monitoring.AimsUse a galactose single point method or combined biochemical parameters to improve assessments of nonalcoholic fatty liver disease in a rat model.MethodsThree nonalcoholic fatty liver disease severities were generated in 50 rats: a control group (n = 18) on a standard diet, and 2 study groups on a choline-deficient diet (n = 18), with and without treatment with silymarin (n = 14). At weeks 4, 8, and 18, a galactose solution (0.5 g/kg/body weight) was rapidly injected intravenously. Sixty minutes later, internal artery blood was taken for biochemical analyses, including galactose. The livers were then removed for haematoxylin–eosin staining and to measure the hepatic lipid content.ResultsAlkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, albumin, and total protein were each significantly correlated with nonalcoholic fatty liver disease severity. Regarding logistic regression, galactose single point method and total protein were significantly predictive. The optimal alanine aminotransferase cutoff point for nonalcoholic fatty liver disease prediction from the receiver-operating characteristic curve had 72.4% sensitivity and 52.4% specificity; galactose single point method alone had 82.8% and 72.4%, whereas galactose single point method + total protein showed 82.8% and 81.0%.ConclusionsBoth galactose single point method and galactose single point method + total protein had greater diagnostic sensitivity and specificity for nonalcoholic fatty liver disease than traditional biochemical tests.     

Branched-chain amino acids alleviate hepatic steatosis and liver injury in choline-deficient high-fat diet induced NASH mice

BackgroundFor successful treatment for nonalcoholic steatohepatitis (NASH), it may be important to treat the individual causative factors. At present, however, there is no established treatment for this disease. Branched-chain amino acids (BCAAs) have been used to treat patients with decompensated cirrhosis.AimIn order to elucidate the mechanisms responsible for the effects of BCAAs on hepatic steatosis and disease progression, we investigated the effects of BCAA supplementation in mice fed a choline-deficient high-fat diet (CDHF), which induces NASH.MethodsMale mice were divided into four groups that received (1) choline-sufficient high fat (HF) diet (HF-control), (2) HF plus 2% BCAA in drinking water (HF-BCAA), (3) CDHF diet (CDHF-control), or (4) CDHF-BCAA for 8 weeks. We monitored liver injury, hepatic steatosis and cholesterol, gene expression related to lipid metabolism, and hepatic fat accumulation.ResultsSerum alanine aminotransferase (ALT) levels and hepatic triglyceride (TG) were significantly elevated in CDHF-control relative to HF-control. Liver histopathology revealed severe steatosis, inflammation, and pericellular fibrosis in CDHF-control, confirming the NASH findings. Serum ALT levels and hepatic TG and lipid droplet areas were significantly lower in CDHF-BCAA than in CDHF-control. Gene expression and protein level of fatty acid synthase (FAS), which catalyzes the final step in fatty acid biosynthesis, was significantly decreased in CDHF-BCAA than in CDHF-control (P < 0.05). Moreover, hepatic total and free cholesterol of CDHF-BCAA was significantly lower than those of CDHF-control.ConclusionsBCAA can alleviate hepatic steatosis and liver injury associated with NASH by suppressing FAS gene expression and protein levels.     

Fisiopatología de la miocardiopatía dilatada isquémica a través del microRNA-16-5p

Introduction and objectivesThe expression levels of microRNA-16-5p (miR-16) are upregulated in ischemic cardiomyopathy and in animal models of ischemic dilated cardiomyopathy (iDCM), inducing myocardial apoptosis. We investigated the role of miR-16 in the adaptive cellular response associated with endoplasmic reticulum (ER) stress and autophagy in the apoptotic iDCM environment.MethodsWe quantified the miR-16 plasma levels of 168 participants—76 controls, 60 iDCM patients, and 32 familial DCM patients with the pathogenic variant of BAG3—by quantitative real-time polymerase chain reaction and correlated the levels with patient variables. The effects of intracellular miR-16 overexpression were analyzed in a human cardiac cell line. Apoptosis and cell viability were measured, as well as the levels of markers associated with ER stress, cardiac injury, and autophagy.ResultsPlasma miR-16 levels were upregulated in iDCM patients (P = .039). A multivariate logistic regression model determined the association of miR-16 with iDCM clinical variables (P < .001). In vitro, miR-16 overexpression increased apoptosis (P = .02) and reduced cell viability (P = .008). Furthermore, it induced proapoptotic components of ER stress, based on upregulation of the PERK/CHOP pathway. However, we observed augmentation of autophagic flux (P < .001) without lysosomal blockade by miR-16 as a possible cytoprotective mechanism.ConclusionsMiR-16 is specifically associated with iDCM. In an ischemic setting, miR-16 activates ER stress and promotes inflammation followed by autophagy in human cardiac cells. Thus, autophagy may be an attempt to maintain cellular homeostasis in response to misfolded/aggregated proteins related to ER stress, prior to apoptosis.     

Consuming a hypocaloric high fat low carbohydrate diet for 12 weeks lowers C-reactive protein,and raises serum adiponectin and high density lipoprotein-cholesterol in obese subjects

ObjectiveHigh fat, low carbohydrate (HFLC) diets have become popular tools for weight management. We sought to determine the effects of a HFLC diet compared to a low fat high carbohydrate (LFHC) diet on the change in weight loss, cardiovascular risk factors and inflammation in subjects with obesity.MethodsObese subjects (29.0–44.6 kg/m²) recruited from Boston Medical Center were randomized to a hypocaloric LFHC (n = 26) or HFLC (n = 29) diet for 12 weeks.ResultsThe age range of subjects was 21–62 years. As a percentage of daily calories, the HFLC group consumed 33.5% protein, 56.0% fat and 9.6% carbohydrate and the LFHC group consumed 22.0% protein, 25.0% fat and 55.7% carbohydrate. The change in percent body weight, lean and fat mass, blood pressure, flow mediated dilation, hip:waist ratio, hemoglobin A1C, fasting insulin and glucose, and glucose and insulin response to a 2 h oral glucose tolerance test did not differ (P > 0.05) between diets after 12 weeks. The HFLC group had greater mean decreases in serum triglyceride (P = 0.07), and hs-CRP (P = 0.03), and greater mean increases in HDL cholesterol (P = 0.004), and total adiponectin (P = 0.045) relative to the LFHC. Secreted adipose tissue adiponectin or TNF-α did not differ after weight loss for either diet.ConclusionsRelative to the LFHC group, the HFLC group had greater improvements in blood lipids and systemic inflammation with similar changes in body weight and composition. This small-scale study suggests that HFLC diets may be more beneficial to cardiovascular health and inflammation in free-living obese adults compared to LFHC diets.     

Alcohol and HBV synergistically promote hepatic steatosis

Background and aimsHepatitis virus and alcohol are the main factors leading to liver damage. Synergy between hepatitis B virus (HBV) and alcohol in promoting liver cell damage and disease progression has been reported. However, the interaction of HBV and ethanol in hepatic steatosis development has not been fully elucidated.MethodsEight-week-old male C57BL/6 mice were treated with or without HBV, ethanol, or the combination of HBV and ethanol (HBV + EtOH), followed by a three-week high-fat diet (HFD) regimen. Liver histology, serum biomarkers, and liver triglyceride levels were analysed. Furthermore, a meta-analysis of the effects of alcohol and HBV on hepatic steatosis in populations was performed.ResultsHepatic steatosis was significantly more severe in the HBV + EtOH group than in the other groups. The serum alanine aminotransferase, aspartate aminotransferase and liver triglyceride levels in the HBV + EtOH group were also significantly higher than those in the other groups. The HBeAg and HBsAg levels in the HBV + EtOH group were significantly higher than those in the pair-fed HBV-infected mice. In addition, the meta-analysis showed that alcohol consumption increased the risk of hepatic steatosis by 43% in HBV-infected patients (pooled risk ratio (RR) = 1.43, P < 0.01).ConclusionsAlcohol and HBV synergistically promote high-fat diet-induced hepatic steatosis in mice. In addition, alcohol consumption increases the risk of hepatic steatosis in HBV-infected patients.     

Hypermethylation of Anti-oncogenic MicroRNA 7 is Increased in Emphysema Patients

IntroductionMicroRNA-7 (miR-7) has a suppressive role in lung cancer and alterations in its DNA methylation may contribute to tumorigenesis. As COPD patients with emphysema have a higher risk of lung cancer than other COPD phenotypes, we compared the miR-7 methylation status among smoker subjects and patients with various COPD phenotypes to identify its main determinants.Methods30 smoker subjects without airflow limitation and 136 COPD patients without evidence of cancer were recruited in a prospective study. Clinical and functional characteristics were assessed and patients were classified into: frequent exacerbator, emphysema, chronic bronchitis and asthma COPD overlap (ACO). DNA collected from buccal epithelial samples was isolated and bisulfite modified. miR-7 methylation status was evaluated by quantitative methylation-specific polymerase chain reaction (qMSP).ResultsmiR-7 Methylated levels were higher in COPD patients than in smokers without airflow limitation (23.7 ± 12.4 vs. 18.5 ± 8.8%, p = 0.018). Among COPD patients, those with emphysema had higher values of methylated miR-7 (27.1 ± 10.2%) than those with exacerbator (19.4 ± 9.9%, p = 0.004), chronic bronchitis (17.3 ± 9.0%, p = 0.002) or ACO phenotypes (16.0 ± 7.2%, p = 0.010). After adjusting for clinical parameters, differences between emphysematous patients and those with other phenotypes were retained. In COPD patients, advanced age, mild-moderate airflow limitation, reduced diffusing capacity and increased functional residual capacity were identified as independent predictors of methylated miR-7 levels.ConclusionThe increase of miR-7 methylation levels experienced by COPD patients occurs mainly at the expense of the emphysema phenotype, which might contribute to explain the higher incidence of lung cancer in these patients.     

Long-Term Effects of Dietary Sodium Intake on Cytokines and Neurohormonal Activation in Patients With Recently Compensated Congestive Heart Failure

BackgroundA growing body of evidence suggests that the fluid accumulation plays a key role in the pathophysiology of heart failure (HF) and that the inflammatory and neurohormonal activation contribute strongly to the progression of this disorder.Methods and ResultsThe study evaluated the long-term effects of 2 different sodium diets on cytokines neurohormones, body hydration and clinical outcome in compensated HF outpatients (New York Heart Association Class II). A total of 173 patients (105 males, mean age 72.5 ± 7) recently hospitalized for worsening advanced HF and discharged in normal hydration and in clinical compensation were randomized in 2 groups (double blind). In Group 1, 86 patients received a moderate restriction in sodium (120 mmol to 2.8 g/day) plus oral furosemide (125 to 250 mg bid); in Group 2, 87 patients: received a low-sodium diet (80 mmol to 1.8 g/day) plus oral furosemide (125 to 250 mg bid). Both groups were followed for 12 months and the treatment was associated with a drink intake of 1000 mL daily. Neurohormonal (brain natriuretic peptide, aldosterone, plasma rennin activity) and cytokines values (tumor necrosis factor-α, interleukin-6) were significantly reduced with a significant increase of the anti-inflammatory cytokine interleukin-10 at 12 months in normal, P < .0001) than low-sodium group. The low-sodium diet showed a significant activation of neurohormones and cytokines and worsening the body hydration, whereas moderate sodium restriction maintained dry weigh and improved outcome in the long term.ConclusionsOur results appear to suggest a surprising efficacy of a new strategy to improve the chronic diuretic response by increasing Na intake and limiting fluid intake. This counterintuitive approach underlines the need for a better understanding of factors that regulate sodium and water handling in chronic congestive HF. A larger sample of patients and further studies are required to evaluate whether this is due to the high dose of diuretic used or the low-sodium diet.     

AT1 Receptor Blockade Prevents the Increase in Blood Pressure and the Augmentation of Intrarenal ANG II Levels in Hypertensive Cyp1a1-Ren2 Transgenic Rats Fed With a High-Salt Diet

IntroductionThis study was performed to determine the effects of high-salt diet on the magnitude of the increases in systolic blood pressure (SBP) and kidney tissue angiotensin (ANG) II levels that occur after induction of ANG II-dependent malignant hypertension in Cyp1a1-Ren2 transgenic rats with inducible expression of the mouse Ren2 renin gene [strain name: TGR(Cyp1a1Ren2)].MethodsCyp1a1- Ren2 rats (n = 6) were fed a normal diet containing 0.3% indole-3- carbinol (I3C) for 10 days to induce ANG II-dependent malignant hypertension.ResultsRats induced with I3C exhibited increases in SBP and elevations of ANG II levels in kidney cortex and medulla. In a second group of rats (n = 6), high-salt intake alone did not alter basal SBP; however, subsequent dietary administration of 0.3% I3C during continued high-salt intake elicited a substantially greater increase in SBP than observed in rats fed a normal salt diet. ANG II levels in kidney cortex and medulla of rats induced with I3C and fed a high-salt diet were elevated similarly to those in rats induced with I3C alone. Chronic administration of the AT₁ receptor antagonist, losartan (100 mg/L in drinking water, n = 6), markedly attenuated the I3C-induced increase in SBP and prevented the augmentation of ANG II levels in kidney cortex and medulla in rats induced with I3C and maintained on a high-salt diet.ConclusionsActivation of AT₁ receptors contributes to the augmented blood pressure and elevated kidney tissue ANG II levels that occur in Cyp1a1-Ren2 transgenic rats with malignant hypertension maintained on a high-salt diet.     

The GLP-1 analog liraglutide attenuates acute liver injury in mice

Introduction and objectivesAcute liver injury is a current health problem with few effective treatments. The present study investigated the hepatoprotective and curative potential of the glucagon-like peptide-1 analog liraglutide against carbon tetrachloride (CCl₄)-induced hepatotoxicity.Materials and methodsMale Swiss mice were subjected to two protocols. The first protocol (Pretreatment) consisted of intraperitoneal (i.p.) treatment with liraglutide (0.057 and 0.118 mg kg⁻¹) or vehicle (distilled water) once daily for 7 days. On days 6 and 7, the animals were challenged with 2% CCl₄ (5 mg kg⁻¹, i.p.). The second protocol (Late treatment) began with an injection of 5% CCl₄ (5 mg kg⁻¹, i.p.) and subsequent treatment with liraglutide (0.057 mg kg⁻¹) or vehicle (distilled water) for 1 day. In both protocols, 24 h after the last administration, blood and bile were collected from anesthetized animals, followed by euthanasia and liver collection. Plasma and bile underwent biochemical analyses, and histological, oxidative stress, and metabolic parameters were evaluated in the liver.ResultsBoth liraglutide treatment protocols attenuated hepatotoxicity that was induced by CCl₄, decreasing plasma levels of hepatic enzymes, stimulating the hepatic antioxidant system, and decreasing centrilobular necrosis, hepatic glycogen, and lipid accumulation. CCl₄ tended to reduce bile lipid excretion, but liraglutide did not influence this parameter.ConclusionsThe present results demonstrated the hepatoprotective and therapeutic effects of liraglutide, which may be attributable to a decrease in liver oxidative stress and the preservation of metabolism. Liraglutide may have potential as a complementary therapy for acute liver injury.     

The high-fat high-fructose hamster as an animal model for niacin’s biological activities in humans

ObjectiveNiacin has been used for more than 50 years to treat dyslipidemia, yet the mechanisms underlying its lipid-modifying effects remain unknown, a situation stemming at least in part from a lack of validated animal models. The objective of this study was to determine if the dyslipidemic hamster could serve as such a model.Materials/MethodsDyslipidemia was induced in Golden Syrian hamsters by feeding them a high-fat, high-cholesterol, and high-fructose (HF/HF) diet. The effect of high-dose niacin treatment for 18 days and 28 days on plasma lipid levels and gene expression was measured.ResultsNiacin treatment produced significant decreases in plasma total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and free fatty acids (FFA), but had no measureable effect on high-density lipoprotein cholesterol (HDL-C) in the dyslipidemic hamster. Niacin treatment also produced significant increases in hepatic adenosine ATP-Binding Cassette A1 (ABCA1) mRNA, ABCA1 protein, apolipoprotein A-I (Apo A-I) mRNA, and adipose adiponectin mRNA in these animals.ConclusionsWith the exception of HDL-C, the lipid effects of niacin treatment in the dyslipidemic hamster closely parallel those observed in humans. Moreover, the effects of niacin treatment on gene expression of hepatic proteins related to HDL metabolism are similar to those observed in human cells in culture. The HF/HF-fed hamster could therefore serve as an animal model for niacin’s lowering of proatherogenic lipids and mechanisms of action relative to lipid metabolism.     

NO levels in diabetes mellitus: Effects of l-NAME and insulin on LCAT,Na+/K+ ATPase activity and lipid profile

ObjectivesDiabetes mellitus (DM) is a chronic disease and one of the most important health problems. Several factors may be responsible for the complications of diabetes mellitus including alterations in the activities of sodium–potassium adenosine triphosphatase (Na⁺/K⁺ ATPase) and lecithin:cholesterol acyltransferase (LCAT) and also levels of nitric oxide (NO). We have investigated the effects of alterations in serum NO levels on activities of erythrocyte membran Na/K ATPase and serum LCAT enzymes.Materials and methodsThe experiments were performed on male rats divided into four groups: group 1, control (standart diet); group 2, diabetic control (single dose of 65 mg/kg of streptozotocin (STZ), i.p); group 3, STZ + insulin (8 IU/kg/day s.c.); group 4 (STZ + l-NAME 5 mg/kg/day orally).ResultStreptozotocin-induced diabetic rats, showed a significant increase in blood glucose and serum cholesterol (C) and triglyceride (TG). Compared to the control group with diabetic group plasma LCAT concentrations and erythrocyte membrane Na⁺/K⁺ ATPase were found to be decreased. Activities of Na⁺/K⁺ ATPase and serum NO level were decreased with the administration of l-NAME. We observed that insulin was ameliorated in all parameters.ConclusionsSerum NO levels is related to erythrocyte membrane Na⁺/K⁺ ATPase activity. But serum NO levels did not affect the plasma LCAT activity and serum lipid profiles.     

Effects of a low glycemic load diet versus a low-fat diet in subjects with and without the metabolic syndrome

Background and aimAlthough many studies report benefits of low glycemic diets, the clinical effects as a whole are mixed. The study aim was to compare a low glycemic load (LGL) diet versus a low-fat diet in a trial with a moderately intense dietary intervention in subjects with varying degrees of metabolic syndrome.Methods and resultsMen and women aged 30–65 years, with a BMI of 28–40 kg/m² (28–35 for women) and at least one criterion of metabolic syndrome were randomized to the two diets. A total of 202 subjects were included, of which 126 (62%) had metabolic syndrome (≥3 criteria). The completion rate was 81%. At 3 months, weight loss was greater in the LGL group (?4.8 ± 3.9 kg versus ?3.8 ± 3.5 kg; P = 0.06) compared to the low-fat group. At 1 year, however, weight loss was similar in both groups (?4.0 ± 5.5 kg versus ?4.3 ± 6.2 kg; n.s.), but waist circumference reduction was less in the LGL group (?3.9 ± 5.3 cm versus ?5.8 ± 6.8 cm; P = 0.03). In contrast, diastolic blood pressure decreased significantly more in the LGL group (?4.0 ± 8.7 mmHg versus ?1.1 ± 8.5 mmHg; P = 0.02). We also observed a significant interaction between the presence of the metabolic syndrome and the effect of the two diets on waist circumference, with a less favorable effect of the LGL diet in subjects without the syndrome (P = 0.039).ConclusionAfter 12 months, both diets reduced body weight and the metabolic disturbances similarly, but the LGL diet appeared more suitable for subjects with metabolic syndrome, and was less effective in those without it.     

La restriction énergétique réduit le stress oxydant de l’aorte et du cœur et corrige le risque athérogène chez le rat rendu obèse

Aim of the studyThe aim was to see if 40% of caloric restriction can improve in rats, the oxidative stress induced by a high fat diet on liver, heart and aorta, and have a positive impact on the lipoproteins-cholesterol contents.MethodsMale Wistar rats (n = 12) consumed at weaning obesegenic diet. The obese rats were divided into two groups (n = 6) each consumed for 4 weeks a normocaloric diet (1,60 MJ) or a calorie restricted diet (40% of energy of the standard diet [0.96 MJ]). A control group (n = 6) was fed a standard diet during the experiment.ResultsCaloric restriction decreased cholesterol and low-density lipoproteins-cholesterol, whereas the high-density lipoproteins-cholesterol was elevated. Levels of cholesterol in the aorta and heart were lowered in the group that consumed caloric restriction compared to normocaloric diet. The values of thiobarbituric acid reactive substances and hydroperoxides were lowered in the aorta and the heart. The caloric restriction compared to normocaloric diet increased positively the superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase activities in the heart and those of catalase and superoxide dismutase in aorta.ConclusionIn obese rats, caloric restriction may play a role in the antioxidant defense of cardiovascular system by reducing proatherogenic cholesterol and lipid peroxidation and increasing the antioxidant activity of some enzymes, which was in favor of reduction of cardiometabolic risk associated with obesity.     

Changes in amino acid profiles and liver alterations in pregnant rats with a high carbohydrate/low protein diet

Introduction and aimIntake of a high-carbohydrate, low-protein diet (HCD/LPD) during pregnancy promotes metabolic disturbances. It has been suggested that liver function during pregnancy contributes to the synthesis of proteins necessary for fetal development during this stage. The liver is a site of response to the synthesis of macronutrients such as proteins. However, it is unknown how HCD/LPD is associated with modifications to the amino acid profiles and hepatic alterations in the maternal environment during pregnancy.Materials and methodsA transverse longitudinal study was done in primiparous mothers during gestation (G) (G1 day 1, G5 day 5, G15 day 15, and G20 day 20). Histological analysis was used to assess hepatic alterations, and amino acid profiles in the liver were analyzed with high performance liquid chromatography (HPLC). Food and water intake was quantified, and peripheral biochemical indicators in serum were measured.ResultsMothers with HCD/LPD had increased micro and macro vesicles of fat, necrosis, and inflammation in the liver on G5. The total concentration of hepatic amino acids increased by 40% on G1, 17% on G5, and 25% on G15; and, there was a 12% decrease on G20. The following increases were observed in the liver on G1: arginine 68%, histidine 75%, alanine 18%, methionine 71%, and phenylalanine 51% (p > 0.05); on G5: arginine 12%, methionine 34%, and phenylalanine 83% (p > 0.05); on G15: arginine and phenylalanine 66%, tryptophan 81% and histidine 60.4% (p > 0.05); and on G20: arginine 32% (p > 0.05). No weight loss, changes in food consumption, or hepatomegaly occurred.ConclusionsHCD/LPD during pregnancy in primiparous mothers may promote development of fat vesicles. Possibly, this condition causes metabolic adaptations and nitrogen management reflected in decreased levels of serum urea and altered amino acid profiles in the liver.