Increased Serum Triglyceride Levels Research Articles

Relationship between serum triglyceride levels and endothelial function in a large community-based study

Background and aimsIt is established that low-density lipoprotein cholesterol is an independent risk factor for cardiovascular events. Recently, circulating triglycerides level has been focused on as a risk factor for cardiovascular events. In this study, we evaluated the associations between triglycerides and endothelial function in a general population. MethodsWe analyzed data for 4887 subjects who were enrolled in the FMD-Japan registry. We investigated cross-sectional associations between serum triglyceride levels and endothelial function assessed by measurement of flow-mediated vasodilation (FMD). ResultsSerum triglyceride levels were correlated with FMD (r = −0.12, p < 0.001). Subjects were divided into six groups based on serum triglyceride levels. FMD was significantly decreased with an increase in serum triglyceride levels (≤0.71 mmol/L, 7.0 ± 3.5%; 0.72–0.94 mmol/L, 6.3 ± 3.5%; 0.95–1.19 mmol/L, 6.0 ± 3.1%; 1.20–1.48 mmol/L, 5.8 ± 3.2%; 1.49–2.02 mmol/L, 5.7 ± 3.1%; ≥2.03 mmol/L, 5.5 ± 3.0%; p for trend <0.001). After adjustment for age, sex, and cardiovascular risk factors, including high-density lipoprotein cholesterol, serum triglyceride levels of more than 1.20 mmol/L were independently associated with the low quartile of FMD (1.20–1.48 mmol/L, odds ratio (OR) 1.41, 95% confidence interval (CI) 1.09 to 1.82; 1.49–2.02 mmol/L, OR 1.31, 95% CI 1.00 to 1.70; ≥2.03 mmol/L, OR 1.48, 95% CI 1.13 to 1.95) using serum triglyceride levels of less than 0.71 mmol/L group as the reference. ConclusionsThese findings suggest that triglycerides are an independent predictor of endothelial function. Lowering circulating triglyceride levels may improve endothelial function, leading to a decrease in cardiovascular events. Clinical trial registration informationURL for Clinical Trial: http://UMIN; Registration Number for Clinical Trial: UMIN000003409

Propofol LCT vs propofol MCT-LCT: Randomized controlled trial

Background: Propofol formulation containing long chain triglycerides (LCT) elicits severe pain on intravenous injection. Newer formulation of propofol containing combination of medium and long chain triglycerides (MCT/LCT;50:50) with less concentration of free propofol may be beneficial in this aspect. Methods: This prospective, randomized, double blind study included 116 ASAI/II adult patients undergoing short surgical procedures under general anesthesia. Patients in group M received 3 cc of MCT/LCT propofol (Fresofol 1%, Fresenius Kabi) and group L received LCT propofol (Diprivan 1%, Astrazeneca), both over 3 seconds (@1cc/sec to assess pain on injection using the VRS score. Induction time and requirement of additional dose of propofol was also noted. Heart rate (HR) and mean arterial pressure (MAP) were recorded at baseline, post intubation and 1, 3, 5 and 10 minutes thereafter. Serum triglyceride levels were measured 24 hours post-surgery and compared to preoperative levels. Results: Group M reported reduced pain score after IV propofol injection (1.37+2.40 vs 2.60+2.93) along with overall less incidence of pain (34.5% vs 53.4%). No difference was found in preoperative and 24 hours postoperative serum triglyceride levels in both groups. Three patients in group L developed thrombophlebitis as compared to one in group M. Induction time and hemodynamics were similar in both groups. Conclusion: MCT/LCT propofol produces less pain on intravenous injection. However, both formulations did not increase serum triglyceride levels after single induction dose. Keywords: Propofol, Anesthesia, Triglycerides, Long chain, Medium chain

A comparative study to illustrate the benefits of using ethinyl estradiol-cyproterone acetate over metformin in patients with polycystic ovarian syndrome

AimThis study was done to illustrate the clinical and biochemical effects of ethinyl estradiol-cyproterone acetate (EE-AC) and metformin in this disease. MethodsThis was a randomized control trial study, done on twenty-six female patients already diagnosed as cases of PCOS. Participants were divided into two study groups: group one (Group 1), received metformin of 500mg twice daily and the second group (Group 2), was given ethinyl estradiol–cyproterone acetate for 21 consecutive days followed by 7 days drug-free. The course of the treatment for both groups was continued for three consecutive months. ResultsGroup 1 showed a statistical significant increase in serum high density lipoprotein cholesterol (HDL-C) levels (P=0.006) and a decrease in the level of triglyceride (TG) (P=0.006). In addition, Group 1 had a significant reduction in the levels of very density lipoprotein cholesterol (VLDL-C) (P=0.006). Group 2 had a significant increase in serum TG levels (P=0.01), associated with a significant decrease in serum LDL-C (P=0.04). Serum testosterone was significantly reduced in group 1 (P=0.038). This was associated with an improvement in glucose tolerance test (GTT) and BMI in the same group (group 1). Group 2, had an improvement in the menstrual cycle control; hirsutism and acne. ConclusionThis study showed that metformin treatment is beneficial in improving serum lipids; glucose homeostasis and BMI, however, the ethinyl estradiol-cyproterone acetate is superior in improving the clinical manifestation of patients with PCOS, including menstrual cycle regulation, hyperandrogenic state.

A Grape Seed Procyanidin Extract Ameliorates Fructose-Induced Hypertriglyceridemia in Rats via Enhanced Fecal Bile Acid and Cholesterol Excretion and Inhibition of Hepatic Lipogenesis.

The objective of this study was to determine whether a grape seed procyanidin extract (GSPE) exerts a triglyceride-lowering effect in a hyperlipidemic state using the fructose-fed rat model and to elucidate the underlying molecular mechanisms. Rats were fed either a starch control diet or a diet containing 65% fructose for 8 weeks to induce hypertriglyceridemia. During the 9th week of the study, rats were maintained on their respective diet and administered vehicle or GSPE via oral gavage for 7 days. Fructose increased serum triglyceride levels by 171% after 9 weeks, compared to control, while GSPE administration attenuated this effect, resulting in a 41% decrease. GSPE inhibited hepatic lipogenesis via down-regulation of sterol regulatory element binding protein 1c and stearoyl-CoA desaturase 1 in the fructose-fed animals. GSPE increased fecal bile acid and total lipid excretion, decreased serum bile acid levels and increased the expression of genes involved in cholesterol synthesis. However, bile acid biosynthetic gene expression was not increased in the presence of GSPE and fructose. Serum cholesterol levels remained constant, while hepatic cholesterol levels decreased. GSPE did not modulate expression of genes responsible for esterification or biliary export of the newly synthesized cholesterol, but did increase fecal cholesterol excretion, suggesting that in the presence of GSPE and fructose, the liver may secrete more free cholesterol into the plasma which may then be shunted to the proximal small intestine for direct basolateral to apical secretion and subsequent fecal excretion. Our results demonstrate that GSPE effectively lowers serum triglyceride levels in fructose-fed rats after one week administration. This study provides novel insight into the mechanistic actions of GSPE in treating hypertriglyceridemia and demonstrates that it targets hepatic de novo lipogenesis, bile acid homeostasis and non-biliary cholesterol excretion as important mechanisms for reducing hypertriglyceridemia and hepatic lipid accumulation in the presence of fructose.

Association of KCNB1 polymorphisms with lipid metabolisms and insulin resistance: a case-control design of population-based cross-sectional study in Chinese Han population.

BackgroundIn our previous study, we had assessed in the Chinese Han population the association of KCNB1 rs1051295 with metabolic traits indicating metabolic syndrome, and showed that KCNB1 rs1051295 genotype TT was associated with increase of waist to hip ratio (WHR), fasting insulin (FINS), triglycerides (TG) and decreased insulin sensitivity at basal condition. Here, we aimed at detecting whether there were associations between other tag SNPs of KCNB1 and favorable or unfavorable metabolic traits.MethodsWe conducted a case–control design of population-based cross-sectional study to investigate the association between each of the 22 candidates tag SNPs of KCNB1 and metabolic traits in a population of 733 Chinese Han individuals. The association was assessed by multiple linear regression analysis or unconditional logistic regression analysis.ResultsWe found that among the 22 selected tag SNPs, four were associated with an increase (rs3331, rs16994565) or decrease (rs237460, rs802950) in serum cholesterol levels; two of these (rs237460, rs802590) further associated or were associated with reduced serum LDL-cholesterol. Two novel tag SNPs (rs926672, rs1051295) were associated with increased serum TG levels. We also showed that KCNB1 rs926672 associated with insulin resistance by a case–control study, and two tag SNPs (rs2057077and rs4810952) of KCNB1 were associated with the measure of insulin resistance (HOMA-IR) in a cross-section study.ConclusionThese results indicate that KCNB1 is likely associated with metabolic traits that may either predispose or protect from progression to metabolic syndrome. This study provides initial evidence that the gene variants of KCNB1, encoding Kv2.1 channel, is associated with perturbation of lipid metabolism and insulin resistance in Chinese Han population.

Metabolic Effects of Two Different Doses of Venlafaxine Therapy on Rats

Abstract Objectives: Venlafaxine is an antidepressant, categorized as a serotonin-norepinephrine reuptake inhibitor (SNRI) with suspected metabolic side effects. The aim of our study was to assess these metabolic effects in rats, using two different doses of venlafaxine. Materials: Three groups of Wistar rats have been treated with venlafaxine during seven weeks. The rats have received a daily dose of 10mg/kg (D1) and 40 mg/kg (D2) while the control group (Dc) has received no treatment. Rats were given “ad libitum” access to food and water. The rats were weighted at treatment day 0, 7, 14, 21, 28, 35, 42 and 49. After completion of venlafaxine treatment, the rats were sacrificed, blood was harvested and the following biochemical parameters have been determined from the centrifuged plasma: triglycerides, glucose and total cholesterol levels. Results: Both the 10 mg/kg and the 40 mg/kg dose venlafaxine therapy resulted in a highly significant increase of rat’s weight. Compared with the control group the mean weight of D1 group has increased with 130.5 ±21.79 g (&lt;0.01) while the mean weight of the second group increased with 94±24.16 g (p&lt;0.01). In addition weight gain of D1 group was significantly higher than that of D2 group (p&lt;0.01). Venlafaxine therapy induced significant increase in serum triglyceride levels (140.04±55.46 mg/dL p&lt;0.01, 83.59±52.85 mg/dL p=0.05). This metabolic effect has been shown to be more evident in case of 10mg/kg dose therapy (p=0.03). Simultaneously, serum cholesterol levels have been reduced, however this decrease proved to be significant only in case of group D2 (p=0.03). Despite of increased triglyceride values, glucose levels were significantly decreased in both treated groups (133.33±36.18mg/dL p=0.05, 118.10±51.98 mg/dL p=0.02). Conclusions: Our results suggest that venlafaxine administrated to rats has unwished dose related metabolic effects such as significant increase in weight and hypertriglyceridemia, however serum cholesterol and plasma glucose levels appears to be decreased by this medication.

Gender-specific increase in susceptibility to metabolic syndrome of offspring rats after prenatal caffeine exposure with post-weaning high-fat diet

Prenatal caffeine exposure (PCE) alters the hypothalamic–pituitary–adrenocortical (HPA) axis-associated neuroendocrine metabolic programming and induces an increased susceptibility to metabolic syndrome (MS) in intrauterine growth retardation (IUGR) offspring rats. High-fat diet (HFD) is one of the main environmental factors accounting for the incidence of MS. In this study, we aimed to clarify the gender-specific increase in susceptibility to MS in offspring rats after PCE with post-weaning HFD. Maternal Wistar rats were administered with caffeine (120mg/kg·d) from gestational day 11 until delivery. The offspring rats with normal diet or HFD were euthanized at postnatal week 24, and blood samples were collected. Results showed that PCE not only reduced serum adrenocorticotropic hormone (ACTH) and corticosterone levels, but also enhanced serum glucose, triglyceride and total cholesterol (TCH) concentrations in the offspring rats. Moreover, several interactions among PCE, HFD and gender were observed by a three-way ANOVA analysis. In PCE offspring, HFD could aggravate the degree of increased serum triglyceride level. Meanwhile, serum corticosterone levels of females were decreased more obviously than those of males in PCE offspring. The results also revealed interactions between HFD and gender in the levels of serum ACTH, triglyceride and TCH, which were changed more evidently in female HFD offspring. These results indicate that HFD could exacerbate the dysfunction of lipid metabolism and the susceptibility to MS induced by PCE, and the female offspring are more sensitive to HFD-induced neuroendocrine metabolic dysfunction than their male counterparts.

Mendelian randomization provides no evidence for a causal role of serum urate in increasing serum triglyceride levels.

Triglycerides and their lipoprotein transport molecules are risk factors for heart disease. Observational studies have associated elevated levels of serum urate (SU) with triglycerides and risk of heart disease. However, owing to unmeasured confounding, observational studies do not provide insight into the causal relationship between SU and triglyceride. The aim of this study was to test for a causal role of SU in increasing triglyceride using Mendelian randomization that accounts for unmeasured confounding. Subjects were of European ancestry from the atherosclerosis risk in communities (n=5237) and Framingham heart (n=2971) studies. Mendelian randomization by the 2-stage least squares regression method was done with SU as the exposure, a uric acid transporter genetic risk score as instrumental variable, and triglyceride as the outcome. In ordinary linear regression, SU was significantly associated with triglyceride levels (β=2.69 mmol/L change in triglyceride per mmol/L increase in SU). However, Mendelian randomization-based estimation showed no evidence for a direct causal association of SU with triglyceride concentration-there was a nonsignificant 1.01 mmol/L decrease in triglyceride per mmol/L increase in SU attributable to the genetic risk score (P=0.21). The reverse analysis using a triglyceride genetic risk score provided evidence of a causal role for triglyceride in raising urate in men (P(Corrected)=0.018). These data provide no evidence for a causal role for SU in raising triglyceride levels, consistent with a previous Mendelian randomization report of no association between SU and ischemic heart disease.

White rice consumption is a risk factor for metabolic syndrome in Tehrani adults: a prospective approach in Tehran Lipid and Glucose Study.

Consumption of white rice has been proposed as a dietary risk factor for development of metabolic disorders and type 2 diabetes, especially in populations who consume white rice as a staple food. In this study, we investigated the association between consumption of white rice and the occurrence of metabolic syndrome in Tehrani adults after 3 years of follow-up. This longitudinal study was conducted within the framework of the Tehran Lipid and Glucose Study on 1476 adults, aged 19-70 years. Dietary intakes were measured using a validated semi-quantitative food frequency questionnaire at baseline. Biochemical and anthropometric measurements were assessed and documented at baseline (2006-2008) and again 3 years later (2009-2011). Multiple logistic regression models were used to estimate the occurrence of the MetS in each quartile of white rice consumption. The mean age of participants was 37.8 ± 12.3 years, and mean BMI was 26.0 ± 4.5 Kg/m2 at baseline. Participants in the highest quartile of white rice consumption were significantly younger, had lower HDL-C levels, and higher systolic and diastolic blood pressures at baseline (P < 0.01). Higher consumption of white rice was also accompanied by higher increase in serum triglyceride levels after the 3-year follow-up (9.9 ± 2.3 vs. 8.2 ± 2.3%, P < 0.01). After adjustment for all potential confounders, the risk of metabolic syndrome in the highest quartile of white rice consumption compared with the lowest, was 1.66 (95% CI: 1.04-2.66). Moreover, participants with central obesity, low physical activity or low-fiber diet had greater risk of metabolic syndrome if white rice constituted ≥25.6% of total energy. We demonstrated that higher consumption of white rice may be a risk factor for development of metabolic syndrome among Iranian adults.

Comparison of serum triglyceride levels with propofol in long chain triglyceride and propofol in medium and long chain triglyceride after short term anesthesia in pediatric patients.

Background:Significant increase in serum triglyceride (ST) concentration have been described in adult population after prolonged administration of propofol formulation containing long chain triglyceride (LCT). Though, medium chain triglyceride-LCT (MCT-LCT) propofol when compared with LCT propofol for long-term sedation in adults resulted in identical triglyceride levels, the elimination of triglyceride was faster in patients administered MCT-LCT propofol.Materials and Methods:A total of 40 children were randomized into two groups of 20 each; Group I were induced with 1% LCT propofol (3 mg/kg) and Group II with 1% medium and LCT propofol and maintained with descalating dose of 20.15 and 10 mg/kg/h at 10 min intervals. Blood samples for ST concentration were obtained before induction of anesthesia, at the end of propofol infusion and 4 h after terminating propofol infusion.Results:ST levels were raised significantly above the basal values in both the groups but the rise was significantly higher in Group I (P < 0.05). Four hours after stopping propofol infusion the triglyceride levels were similar to the basal values in Group II, whereas in Group I the values were significantly greater than the baseline (P < 0.05) as well as those of Group II (P < 0.05). No clinically significant adverse effect of hypertriglyceridemia was observed.Conclusion:Even short term anesthesia with LCT and MCT-LCT propofol (1%) leads to elevated ST levels. The increase in ST levels is less with MCT-LCT propofol and elimination of triglyceride is also rapid after terminating MCT-LCT propofol infusion.

Korean red ginseng combined with nattokinase ameliorates dyslipidemia and the area of aortic plaques in high cholesterol-diet fed rabbits

Male white rabbits were fed a high cholesterol diet supplemented with red ginseng (RG) or red ginseng plus nattokinase (RGNK). RG and RGNK significantly reduced increased serum triglycerides levels and aortic plaque area in a hypercholesterol diet fed rabbits. Moreover, only RGNK reduced hepatic cholesterol and cholesteryl ester transfer protein activity levels. Therefore, the present study suggests RGNK might be a potential therapeutic approach for atherogenesis.

Thyroid Hormone Modulates Food Intake and Glycemia via Ghrelin Secretion in Zucker Fatty rats

Hyperthyroidism is known to increase food intake and central administration of thyroid hormone shows acute orexigenic effects in rodents. We investigated whether T3 influences appetite and glucose homeostasis by modulating circulating ghrelin, an important orexigenic hormone, in Zucker fatty rats. The acute anorectic effects of T3 and ghrelin mimetic MK-0677 were studied in rats trained for fasting induced food intake. The serum concentration of T3, ghrelin, glucose, triglycerides, and liver glycogen were estimated. The involvement of sympathetic nervous system was evaluated by conducting similar experiments in vagotomized rats. T3 increased food intake and glucose in rats over 4 h, with increase in serum T3 and decrease in liver glycogen. T3 treatment was associated with increase in serum ghrelin. An additive effect on appetite and glucose was observed when T3 (oral) was administered with central (intracerebroventricular) administration of a ghrelin mimetic, MK-0677. Ghrelin antagonist, compound 8a, antagonized the hyperglycemic and hyperphagic effects of T3. In vagotomized rats, T3 did not show increase in appetite as well as glucose. Serum ghrelin levels were unchanged in these animals after T3 treatment. However, T3 showed increase in serum triglyceride levels indicating its peripheral lipolytic effect, in vagotomized as well as sham treated animals. To conclude, acute orexigenic and hyperglycemic effects of T3 are associated with ghrelin secretion and activity. This effect seems to be mediated via vagus nerves, and is independent of glucoregulatory hormones.

Fast food consumption and the risk of metabolic syndrome after 3-years of follow-up: Tehran Lipid and Glucose Study

There are growing concern globally regarding fast food consumption and its related cardiometabolic outcomes. In this study we investigated whether fast food consumption could affect the occurrence of metabolic syndrome (MetS) after 3-years of follow-up in adults. This longitudinal study was conducted in the framework of Tehran Lipid and Glucose Study on 1476 adults, aged 19-70 y. The usual intakes of participants were measured using a validated semi-quantitative food frequency questionnaire at baseline. Biochemical and anthropometric measurements were assessed at baseline (2006-2008) and 3 years later (2009-2011). Multiple logistic regression models were used to estimate the occurrence of the MetS in each quartile of fast food consumption. The mean age of participants was 37.8±12.3 y, and mean BMI was 26.0±4.5 kg/m(2) at baseline. Participants in the highest quartile of fast food consumption were younger (33.7 vs 43.4 years, P<0.01). Higher consumption of fast food was accompanied with more increase in serum triglyceride levels and triglyceride to HDL-C ratio after the 3-year follow-up. After adjustment for all potential confounding variables, the risk of metabolic syndrome, in the highest quartile of fast foods compared with the lowest, was 1.85 (95% CI=1.17-2.95). The effects of fast food consumption on the occurrence of MetS were more pronounced in younger adults (<30 years), and participants who had greater wait to hip ratio, consumed less phytochemical-rich foods or had low-fiber diet (P<0.05). We demonstrated that higher consumption of fast foods had undesirable effects on metabolic syndrome after 3-years of follow-up in Iranian adults.

The calcium-sensing receptor R990G polymorphism is associated with increased risk of hypertriglyceridemia in obese Chinese

BackgroundWe have demonstrated that the calcium-sensing receptor (CaSR) is involved in lipid metabolism; however, whether CaSR polymorphisms affect lipid metabolism in obesity is still unclear. The present study aimed to determine the effects of CaSR polymorphisms on HTG risk in obese Chinese. MethodsA total of 972 subjects with HTG and 1197 with normal triglyceride (NTG) were stratified by body mass index (BMI) into normal weight, overweight or obesity subgroups. After 12-h fasting, CaSR polymorphisms in exon 7 were determined in the blood. Serum lipids and glucose, as well as height, body weight and waist circumference were measured. The anthropometric and metabolic characteristics of the NTG subjects were re-evaluated 3years later. ResultsThere were no genotypic or allelic distribution differences for the A986S or Q1011E polymorphisms between the NTG and HTG groups. However, the G/G genotypic and G allelic distributions of the CaSR R990G polymorphism in the HTG group were higher than the NTG group (p<0.001). After stratification, in obese subjects, the homozygous (G/G) distribution of the CaSR R990G polymorphism in the HTG group was significantly higher than in the NTG group (p=0.001), and showed an increased risk of HTG at baseline [OR=2.55, 95% CI=1.65–3.92, p<0.006]. Interaction of the CaSR R990G polymorphism with BMI was associated with increased risk of HTG (β=0.927, p<0.001). Re-evaluation of the NTG subjects revealed significantly increased serum triglyceride levels in obese homozygous versus wildtype carriers (p<0.05). ConclusionsThese results suggest that the CaSR R990G polymorphism is associated with increased risk of HTG, especially in obese Chinese, and may be a potential genetic predictor of diseases related to HTG.

Carnitine Deficiency and its Possible Risk Factors in TB Patients: First Report

To assess carnitine serum levels and possible risk factors of its deficiency in patients with TB. All newly diagnosed TB patients admitted to an infectious diseases ward were recruited. Demographic, clinical and paraclinical characteristics of the patients were collected. Total carnitine serum concentrations were measured. To investigate factors that can predict carnitine deficiency, logistic regression analysis with odds ratio and 95% CI was performed. The mean ± standard deviation of carnitine serum levels of patients was 43.77 ± 32.92 µmol/l. Carnitine deficiency was detected in 47.7% of the study population. According to the final model of multivariate logistic regression analysis, increased serum triglyceride levels and hypoalbuminemia were identified as predictive factors of carnitine deficiency in TB patients aged over 35 years old. Nearly half of Iranian patients with TB were carnitine-deficient. Increased serum triglyceride levels and hypoalbuminemia were identified as independent risk factors of carnitine deficiency in patients aged over 35 years. Considering malnutrition as a major risk factor of TB and the safety of carnitine supplementation, use of carnitine as an adjunctive modality instead of other standard interventions may show beneficial effects in patients with TB.

Association of ADRB2 polymorphism with triglyceride levels in Tongans

BackgroundOur previous study demonstrated that the A-allele of the single nucleotide polymorphism (SNP) rs34623097 located in the upstream region of the β2 adrenergic receptor gene (ADRB2) is significantly associated with risk for obesity in Oceanic populations.MethodsTo investigate whether the ADRB2 polymorphisms explain part of the individual differences in lipid mobilization, energy expenditure and glycogen breakdown, the associations of 10 ADRB2 SNPs with total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and triglyceride levels were examined in 128 adults in Tonga.ResultsA multiple linear regression analysis adjusted for age, sex, and body mass index revealed that rs34623097 was significantly associated with triglyceride levels (P-value = 0.037). A copy of the rs34623097-A allele increased serum triglyceride levels by 70.1 mg/dL (0.791 mmol/L). None of the ADRB2 SNPs showed a significant association with total-cholesterol, high-density lipoprotein cholesterol, or low-density lipoprotein cholesterol.ConclusionsIn a Tongan population, a SNP located in the upstream region of ADRB2 is associated with triglyceride levels independent of body mass index.

You are what you eat-Do not blame your mother.

You are what you eat-Do not blame your mother.

Effects on Gene Expression in Rat Liver after Administration of RXR Agonists: UAB30, 4-Methyl-UAB30, and Targretin (Bexarotene)

Examination of three retinoid X receptor (RXR) agonists [Targretin (TRG), UAB30, and 4-methyl-UAB30 (4-Me-UAB30)] showed that all inhibited mammary cancer in rodents and two (TRG and 4-Me-UAB30) strikingly increased serum triglyceride levels. Agents were administered in diets to female Sprague-Dawley rats. Liver RNA was isolated and microarrayed on the Affymetrix GeneChip Rat Exon 1.0 ST array. Statistical tests identified genes that exhibited differential expression and fell into groups, or modules, with differential expression among agonists. Genes in specific modules were changed by one, two, or all three agonists. An interactome analysis assessed the effects on genes that heterodimerize with known nuclear receptors. For proliferator-activated receptor α/RXR-activated genes, the strongest response was TRG > 4-Me-UAB30 > UAB30. Many liver X receptor/RXR-related genes (e.g., Scd-1 and Srebf1, which are associated with increased triglycerides) were highly expressed in TRG and 4-Me-UAB30- but not UAB30-treated livers. Minimal expression changes were associated with retinoic acid receptor or vitamin D receptor heterodimers by any of the agonists. UAB30 unexpectedly and uniquely activated genes associated with the aryl hydrocarbon hydroxylase (Ah) receptor (Cyp1a1, Cyp1a2, Cyp1b1, and Nqo1). Based on the Ah receptor activation, UAB30 was tested for its ability to prevent dimethylbenzanthracene (DMBA)-induced mammary cancers, presumably by inhibiting DMBA activation, and was highly effective. Gene expression changes were determined by reverse transcriptase-polymerase chain reaction in rat livers treated with Targretin for 2.3, 7, and 21 days. These showed similar gene expression changes at all three time points, arguing some steady-state effect. Different patterns of gene expression among the agonists provided insight into molecular differences and allowed one to predict certain physiologic consequences of agonist treatment.

Fenofibrate, a peroxisome proliferator-activated receptor α-agonist, blocks lipopolysaccharide-induced inflammatory pathways in mouse liver.

Backgrounds/AimsDuring the acute phase response, cytokines induce marked alterations in lipid metabolism including an increase in serum triglyceride levels and a decrease in hepatic fatty acid oxidation, in bile acid synthesis, and in high-density lipoprotein levels.MethodsPeroxisome proliferator-activated receptors (PPARs: PPARα, β/δ, and γ) regulate fatty acid metabolism, glucose homeostasis, cell proliferation, differentiation and inflammation. Proinflammatory profiles including tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) are the important pathological factors in inflammatory responses during the pathological progression of the acute phase response. Lipopolysaccarides (LPS) induced the expression of TNF-α, IL-1β, and IL-6. LPS-induced inflammation decrease the expression of peroxisome proliferator-activated receptor α (PPARα), PPARβ/δ, PPARγ, and coactivators PPARγ co-activator 1 α (PGC-1α), PGC-1β messenger RNA (mRNA) in the liver of Balb/c mouse. In addition, LPS-induced inflammation diminishes the protein level of PPARα, PPARβ/δ, and PPARγ. Proinflammatory cytokines including TNFα, IL-1β, and IL-6 are the principal reducer of PPARs. However, the knockout mouse model against TNFα and IL-6 does not block decrease of PPARs in serum and liver. The mice were pretreated with fenofibrate at 100 mg/kg for 2 days.ResultsThese treatment protocols increased the amount of PPARs mRNA in the liver. Fenofibrate inhibited LPS-induced TNF-α, IL-1β, and IL-6 production in the serum and liver. Similar results were obtained when human hepatoma HepG2 cells exposed to LPS were co-incubated with fenofibrate. LPS-treated HepG2 cells decreased expression of IκB. Moreover, activation of PPARs abrogated LPS-induced degradation of IκB, thus suppressing LPS-induced NF-κB activities.ConclusionsTherefore, fenofibrate decreases the expression and secretion of TNF-α, IL-1β, and IL-6 via the NF-κB signaling pathway, thus serving as therapeutic targets to attenuate inflammation that is involved in hepatic pathological progression.

Serum Lipid Profile status of Type 2 Diabetic Patients in the cross section population in Dhaka City of Bangladesh

Objectives: Serum lipid profile viz the level of total cholesterol (TC), Triglyceride (TG), HDL-cholesterol and LDL-cholesterol of type2 diabetic patients have been studied and compares them with levels of control subjects. Results: The mean value of the TG level for male diabetics was higher than that for the female diabetics and the mean values of TC, HDL-C and LDL-C were not found significantly different between male and female diabetics. Hyperlipidemia has a documented causative relation with CAD, but the major risk associated with diabetes may be due to the associated hyperlipidemia. The study revealed that dyslipidemia is very common in type2 diabetics and the most common abnormality observed was increased serum triglyceride levels (58%). The next common abnormality was decreased serum high-density lipoprotein cholesterol (HDL-C) levels and increased serum low-density lipoprotein cholesterol (LDL-C) levels. A high total serum cholesterol levels was found in 41% patients. 39% of the patients examined were overweight, and 7% were overtly obese. Conclusion: Thus, the study clearly shows the relationship between type2 diabetes and hyperlipidemia, which may influence the mechanism by which type2 diabetes is associated with increased CAD risk. DOI: http://dx.doi.org/10.3329/bjms.v11i2.11479 Bangladesh Journal of Medical Science Vol. 11 No. 02 April 2012: 121-125