Lipids in Health and Disease Latest Content

NPC1L1 inhibitor ezetimibe is a reliable therapeutic agent for non-obese patients with nonalcoholic fatty liver disease

Munechika Enjoji — 2010-03-12T00:00:00Z

Background: We recently examined the distribution of abdominal fat, dietary intake and biochemical data in patients with nonalcoholic fatty liver disease (NAFLD) and found that non-obese NAFLD patients did not necessarily exhibit insulin resistance and/or dysregulated secretion of adipocytokines. However, dietary cholesterol intake was superabundant in non-obese patients compared with obese patients, although total energy and carbohydrate intake was not excessive. Therefore, excess cholesterol intake appears to be one of the main factors associated with NAFLD development and liver injury. Methods: We reviewed a year of follow-up data of non-obese NAFLD patients treated with Niemann-Pick C1 like 1 inhibitor ezetimibe to evaluate its therapeutic effect on clinical parameters related to NAFLD. Without any dietary or exercise modification, 10 mg/day of ezetimibe was given to 8 patients. In 4 of 8 patients, ezetimibe was administered initially. In the remaining 4 patients, medication was switched from ursodeoxycholic acid to ezetimibe. Results: In each patient, body mass index was maintained under 25 kg/m2 during the observation period. Serum ALT levels significantly decreased within 6 months and in 4 patients levels reached the normal range (<30 U/L), which was accompanied with at least a 10% decrease in serum total cholesterol and LDL-cholesterol. However, ultrasonographic findings of fatty liver did not show obvious improvement for a year. Conclusion: We conclude that the cholesterol absorption inhibitor ezetimibe can suppress hepatic injury in non-obese patients with NAFLD and that ezetimibe may offer a novel treatment for NAFLD.

Association of LIPC -250G>A polymorphism and several environmental factors with serum lipid levels in the Guangxi Bai Ku Yao and Han populations

Li Meng — 2010-03-11T00:00:00Z

Background: The association between -250G>A polymorphism in the promoter region of the hepatic lipase gene (LIPC) and plasma high-density lipoprotein cholesterol (HDL-C) concentration is contradictory in diverse ethnics. Bai Ku Yao is an isolated subgroup of the Yao minority in China. This study was designed to detect the association of LIPC -250G>A (rs2070895) polymorphism and several environmental factors with serum lipid levels in the Guangxi Bai Ku Yao and Han populations. Methods: A total of 778 subjects of Bai Ku Yao and 648 participants of Han Chinese aged 15-80 were randomly selected from our previous stratified randomized cluster samples. Genotyping of the LIPC -250G>A was performed by polymerse chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. Results: The levels of serum total cholesterol (TC), HDL-C, low-density lipoprotein cholesterol (LDL-C) and apolipoprotein (apo) AI were lower in Bai Ku Yao than in Han (P<0.01 for all). The frequencies of GG, GA and AA genotypes were 50.0%, 43.3% and 6.7% in Bai Ku Yao, and 35.7%, 50.6% and 13.7% in Han (P<0.01); respectively. The frequencies of G and A alleles were 71.7% and 28.3% in Bai Ku Yao, and 61.0% and 39.0% in Han (P<0.01). The levels of HDL-C and the ratio of apoAI to apoB in Bai Ku Yao were lower in GG genotype than in GA or AA genotype (P<0.05~0.01). The levels of TC, HDL-C, LDL-C and apoB in Han were lower in GG genotype than in GA or AA genotype (P<0.05-0.01). The levels of HDL-C and the ratio of apoAI to apoB in Bai Ku Yao, and the levels of HDL-C, LDL-C and apoB in Han were correlated with genotype and/or allele (P<0.05 for all). Serum lipid parameters were also correlated with age, sex, alcohol consumption, cigarette smoking, blood pressure, body weight, and body mass index in both ethnic groups. Conclusions: The differences in the lipid profiles between the two ethnic groups might partly result from different genotypic frequency of LIPC -250G>A or different LIPC-enviromental interactions.

Evaluation of different formulas for LDL-C calculation

Ana Vujovic — 2010-03-10T00:00:00Z

Background: Friedewald's formula for the estimation of LDL-C concentration is the most often used formula in clinical practice. A recent formula by Anandaraja and colleagues for LDL-C estimation still needs to be evaluated before it is extensively applied in diagnosis. In the present study we validated existing formulas and derived a more accurate formula to determine LDL-C in a Serbian population. Methods: Our study included 2053 patients with TG [less than or equal to] 4.52 mmol/L. In an initial group of 1010 patients, Friedewald's and Anandaraja's formulas were compared to a direct homogenous method for LDL-C determination. The obtained results allowed us to modify Friedewald's formula and apply it in a second group of patients. Results: The mean LDL-C concentrations were 3.9 +/- 1.09 mmol/L, 3.63 +/- 1.06 mmol/L and 3.72 +/- 1.04 mmol/L measured by a direct homogenous assay (D-LDL-C), calculated by Friedewald's formula (F-LDL-C) and calculated by Anandaraja's formula (A-LDL-C), respectively in the 1010 patients. The Student's paired t-test showed that D-LDL-C values were significantly higher than F-LDL-C and A-LDL-C values (p < 0.001). The Passing-Bablok regression analysis indicated good correlation between calculated and measured LDL-Cs (r > 0.89). Using lipoprotein values from the initial group we modified Friedewald's formula by replacing the term 2.2 with 3. The new modified formula for LDL-C estimation (S-LDL-C) showed no statistically significant difference compared to D-LDL-C. The absolute bias between these two methods was - 0.06 +/- 0.37 mmol/L with a high correlation coefficient (r = 0.96). Conclusions: Our modified formula for LDL-C estimation appears to be more accurate than both Friedewald's and Anandaraja's formulas when applied to a Serbian population.

The changes in various hydroxyproline fractions in aortic tissue of rabbits are closely related to the progression of atherosclerosis

Mohamed Abdelhalim — 2010-03-09T00:00:00Z

Background: The most important function of collagen and elastin is to induce several mechanical parameters which are known to play a dominant role in governing mechanical properties of the blood vessels. The aortic tissue of rabbit is one of the important sources of collagen and elastin. The effects of high fat diet (HFD) on the hydroxyproline (Hyp) fractions in serum and aortic tissues of rabbits and collagen content in the aortic tissues of rabbits have not been documented before. The present study was undertaken to investigate the changes in Hyp fractions in serum and aortic tissues of rabbits and collagen content in the aortic tissues of rabbits during the progression of atherosclerosis. The atherosclerotic model used in this study was the New Zealand white rabbit (male; 12 weeks old). Twenty five rabbits were individually caged, and divided into control group (NOR; n = 10) and HFD group (CHO; n = 15). The control group was fed (100 g/day) of normal (NOR) diet for a period of 15 weeks. The HFD group was fed normal diet supplemented with 1.0% cholesterol plus 1.0% olive oil (100 g/day) for the same period of time. Results: We found that the TC, LDLC, and TG (mg/dl) were significantly (p< 0.001) increased in HFD rabbits compared with control rabbits with percentage normalized changes of 1198%, 1591%, and 710%, respectively. The peptide-bound Hyp in the serum was significantly (P< 0.05) increased in HFD rabbits compared with control rabbits with percentage normalized change of 517% while it significantly (P < 0.01) decreased in aortic tissues of HFD rabbits compared with control rabbits with percentage normalized change of 65%. The protein-bound Hyp in the serum was significantly (P < 0.01) increased in HFD rabbits compared with control rabbits with percentage normalized change of 100%; the protein-bound Hyp in the aortic tissues of control rabbits was 235.30 +/- 55.14 (Mean +/- SD) while it was not detectable (ND) in HFD rabbits. Total serum Hyp showed no significant (P< 0.05) change in HFD rabbits compared with control rabbits while it was significantly (P < 0.05) decreased in aortic tissues of HFD rabbits compared with control rabbits with percentage normalized change of 73%. The total collagen was significantly (p< 0.01) decreased in aortic tissues of HFD rabbits compared with control rabbits with percentage normalized change of 73% which was supported by histological study. Conclusions: These results suggest that percentage decrease in various Hyp fractions in aortic tissue of HFD rabbits are closely related to percentage decrease of collagen content in aortic tissues of HFD rabbits. These results also suggest that it may be possible to use the changes in various Hyp fractions in aortic tissues of rabbits as an important risk factor during the progression of atherosclerosis.

Dietary saponins of sea cucumber alleviate orotic acid-induced fatty liver in rats via PPAR alpha and SREBP-1c signaling

Xiao-Qian Hu — 2010-03-09T00:00:00Z

Background: Nonalcoholic fatty liver disease is the most common chronic liver disease in the world, and is becoming increasingly prevalent. Saponins of sea cucumber (SSC) are proven to exhibit various biological activities. Therefore, the present study was undertaken to examine the effect of saponins extracted from sea cucumber (Pearsonothuria graeffei) on the preventive activity of fatty liver in rats. Methods: Male Wistar rats were randomly divided into five groups, including normal control group, fatty liver model group, SSC-treated group with SSC at levels of 0.01 %, 0.03 % and 0.05 %. Model rats were established by administration with 1% orotic acid (OA). After the experiment period, serum total cholesterol (TC), triglyceride (TG), and hepatic lipid concentrations were determined. To search for a possible mechanism, we examined the changes of key enzymes and transcriptional factors involved in hepatic lipids biosynthesis, fatty acid beta-oxidation. Results: Both 0.03% and 0.05 % SSC treatment alleviated hepatic steatosis and reduced serum TG and TC concentration significantly in OA fed rats. Hepatic lipogenic enzymes, such as fatty acid synthase (FAS), malic enzyme (ME), and glucose-6-phosphate dehydrogenase (G6PDH) activities were inhibited by SSC treatment. SSC also decreased the gene expression of FAS, ME, G6PDH and sterol-regulatory element binding protein (SREBP-1c). Otherwise, the rats feeding with SSC showed increased carnitine palmitoyl transferase (CPT) activity in the liver. Hepatic peroxisome proliferator-activated receptor alpha (PPAR alpha), together with its target gene CPT and acyl-CoA oxidase (ACO) mRNA expression were also upregulated by SSC. Conclusions: According to our study, the lipids-lowering effect of dietary SSC may be partly associated with the enhancement of beta-oxidation via PPAR alpha activation. In addition, the inhibited SREBP-1c- mediated lipogenesis caused by SSC may also contribute to alleviating fatty liver.

Fatty acid extracts from Lucilia sericata larvae promote murine cutaneous wound healing by angiogenic activity

Zhen Zhang — 2010-03-08T00:00:00Z

Background: fatty acids are considered to be effective components to promote wound healing and Lucilia sericata larvae are applied clinically to treat intractable wounds. We aimed to investigat the effect of fatty acid extracts from dried Lucilia sericata larvae on murine cutaneuous wound healing as well as angiogenesis. Results: On day 7 and 10 after murine acute excision wounds creation, the percent wound contraction of fatty acid extracts group was higher than that of vaseline group. On day 3, 7 and 10 after wounds creation, the wound healing quality of fatty acid extracts group was better than that of vaseline group on terms of granulation formation and collagen organization. On day 3 after wounds creation, the micro vessel density and vascular endothelial growth factor expression of fatty acid extracts group were higher than that of vaseline group. Component analysis of the fatty acid extracts by gas chromatography-mass spectrometry showed there were 10 kinds of fatty acids in total and the ratio of saturated fatty acid, monounsaturated fatty acid and polyunsaturated fatty acid (PUFA) was: 20.57%:60.32%:19.11%. Conclusions: Fatty acid extracts of dried Lucilia sericata larvae, four fifths of which are unsaturated fatty acids, can promote murine cutaneous wound healing probably resulting from the powerful angiogenic activity of the extracts.

Comparative antilipidemic effect of N-acetylcysteine and sesame oil administration in diet-induced hypercholesterolemic mice

Laskarina-Maria Korou — 2010-03-06T00:00:00Z

Background: There is an increasing number of novel antilipidemic therapies under consideration. The putative hypolipidemic effect of N-acetylcysteine (NAC) and sesame oil was studied in a mouse model of dietary-induced hypercholesterolemia. Methods: Male C57bl/6 mice were assigned to the following groups: (NC) control group, (HC) group receiving test diet supplemented with 2% cholesterol and 0.5% cholic acid for 8 weeks, (HCN) group receiving the test diet with NAC supplementation (230 mg/kg p.o.) and (HCS) group fed the test diet enriched with 10% sesame oil. Total serum cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides were assayed at the beginning and at the end of the experiment. Total peroxides and nitric oxide (NO) levels were measured in the serum at the end of the experiment. Hepatic and aortic lesions were evaluated by haematoxylin-eosin staining. Results: Higher serum levels of total and LDL-cholesterol were recorded in all groups fed the high cholesterol diet. The HCN group presented reduced lipid levels compared to HC and HCS groups. No differences were observed between HCS and HC groups. Peroxide content in serum was markedly increased in mice consuming high cholesterol diet. NAC and sesame oil administration led to a significant decrease of serum lipid peroxidation in the levels of control group, whereas only NAC restored NO bioavailability. In terms of liver histology, the lesions observed in HCN group were less severe than those seen in the other high cholesterol groups. Conclusion: Co-administration of NAC, but not sesame oil, restored the disturbed lipid profile and improved hepatic steatosis in the studied diet-induced hypercholesterolemic mice. Both agents appear to ameliorate serum antioxidant defense.

Postnatal ontogenesis of clock genes in mouse suprachiasmatic nucleus and heart

Jie Huang — 2010-03-05T00:00:00Z

Background: The master clock within the hypothalamic suprachiasmatic nucleus (SCN) synchronizing clocks in peripheral tissues is entrained by the environmental condition, such as the light-dark (LD) cycle. The mechanisms of circadian clockwork are similar in both SCN and peripheral tissues. The aim of the present work was to observe the profiles of clock genes expression in mouse central and peripheral tissues within postnatal day 5 (P5).The daily expression of four clock genes mRNA (Bmal1, Per2, Cry1 and Rev-erb alpha) in mouse SCN and heart was measured at P1, P3 and P5 by real-time PCR. Results: All the studied mice clock genes began to express in a circadian rhythms manner in heart and SCN at P3 and P5 respectively . Interestingly, the daily rhythmic phase of some clock genes shifted during the postnatal days. Moreover, the expressions of clock genes in heart were not synchronizeed with those in SCN until at P5. Conclusion: The data showed the gradual development of clock genes in SCN and a peripheral tissue, and suggested that development of clock genes differed between in the SCN and the heart. Judging from the mRNA expression, it was possible that the central clock synchronized the peripheral clock as early as P5.

Influence of co-existing atrial fibrillation on the efficacy of atorvastatin treatment in patients with dilated cardiomyopathy: a pilot study

Agata Dabrowa-Bielecka — 2010-02-23T00:00:00Z

IntroductionThe aim of the study was to assess the influence of co-existing atrial fibrillation (AF) on inflammatory condition factors, left ventricular function, clinical course and the efficacy of statin treatment of congestive heart failure in the course of dilated cardiomyopathy (DCM).Material and methodsIn a prospective, randomized, open-label study, 69 patients with DCM and left ventricular ejection fraction (LVEF) ≤40% were divided into two groups, with and without AF, who were treated according to the recommended standards. 68% of patients from the group with AF and 59% of patients from the group without AF were administered atorvastatin 40 mg daily for 8 weeks and 10 mg for next 4 months. Clinical examination with the assessment of body mass index (BMI) and waist size were followed by routine laboratory tests, measurement of concentration of tumor necrosis factor (TNF-α), interleukin-6 (IL-6), and IL-10 in blood plasma, N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration in blood serum, echocardiographic examination, and the assessment of exercise capacity in 6-minute walk test (6-MWT). After six months, morbidity rate and the number of heart failure hospitalizations were also observed. Results: In the whole population of patients, a significantly higher concentration of NT-proBNP was observed in the AF group (2669 ± 2192 vs 1540 ± 1067, p = 0.02). After statin treatment, in patients with DCM and co-existing AF, higher values of NT-proBNP and IL-6 were observed compared to non-AF patients (1530 ± 1054 vs 1006 ± 1195, p = 0.04 and (14.16 ± 13.40 vs 6.74 ± 5.45, p = 0.02, respectively). Conclusion: In patients with DCM and co-existing AF, a weaker effect of atorvastatin concerning the reduction of IL-6 and NT-proBNP concentration was observed than in patients without atrial fibrillation.Trials Registration(ClinialTrial.gov No.: NCT01015144)

The use of LeptiCore in reducing fat gain and managing weight loss in patients with metabolic syndrome

Dieudonne Kuate — 2010-02-19T00:00:00Z

Background: LeptiCore® is a proprietary combination of various ingredients which have been shown to have properties which could be beneficial to weight loss in obese and overweight human subjects. This study evaluates the effect of Lepticore® on bodyweight as well as parameters associated with obesity and metabolic syndrome. Methods: The study was an 8 week randomized, double-blind, placebo-controlled design involving 92 obese (mean BMI > 30 kg/m2) participants (37 males; 55 females; ages 19-52; mean age = 30.7). The participants were randomly divided into three groups: placebo (n = 30), LeptiCore® formula A (low dose) (n = 31) and LeptiCore® formula B (high dose) (n = 31). Capsules containing the placebo or active formulations were administered twice daily before meals with 300 ml of water. None of the participants followed any specific diet nor took any weight-reducing medications for the duration of the study. A total of 12 anthropomorphic and serological measurements were taken at the beginning of the study and after 2, 4, 6, and 8 weeks of treatment. Results: Compared to the placebo group, the two active groups showed statistically significant differences on all 12 variables by week 8. These included four anthropomorphic variables (body weight, body fat, waist and hip size) and eight measures of serological levels (plasma total cholesterol, LDL, HDL, triglycerides, blood glucose, serotonin, leptin, C-reactive protein). The two active groups also showed significant intra-group differences on all 12 variables between study onset and week 8. Conclusion: The LeptiCore® formulation at both the low and high dosages appears to be helpful in the management of fat gain and its related complications. The higher dosage resulted in significantly greater reductions in body weight and triglyceride, blood glucose, and C-reactive protein levels, as well as increased serotonin levels.