Inhibition of MEK/ERK1/2 Signaling Affects the Fatty Acid Composition of HepG2 Human Hepatic Cell Line.

INTRODUCTION: The extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase pathway, also known as the MEK/ERK1/2 kinase cascade, has recently been implicated in the regulation of lipid metabolism and fatty liver disease. However, its functional effect on cellular fatty acid composition is unknown. Herein, we examined the effect of a pharmacological inhibitor of MEK, the upstream kinase activator of ERK1/2, on fatty acid composition of hepatocellular carcinoma cell line HepG2. METHODS: HepG2 cells cultured in RPMI-1640 were exposed to the commonly used ERK1/2 pathway inhibitor PD98059 and were investigated with respect to fatty acid composition by gas-liquid chromatography. RESULTS: Exposure of cells to the ERK1/2 pathway inhibitor induced an increase in monounsaturated fatty acids and the fatty acid desaturation index and a decrease in polyunsaturated fatty acid content. Specifically, we showed a significant increase of oleic acid (18:1n-9; +29%, P=0.003) and arachidonic acid (20:4n-6)/linoleic acid (18:2n-6) ratio (3.5-fold; P<0.001) in HepG2 cells. CONCLUSION: Cellular fatty acid composition of HepG2 cells appeared to be differentially regulated by ERK1/2 pathway, thus suggesting related metabolic pathways as potential mediators of the effects of ERK1/2 signaling on hepatic fatty acid composition.

Plasma Leptin, hTERT Gene Expression, and Anthropometric Measures in Obese and Non-Obese Women with Breast Cancer.

INTRODUCTION: Expression of human telomerase reverse transcriptase (hTERT) occurs in most cancers but its relation with obesity is unclear. This study explores the association between leptin levels and anthropometric indices with hTERT mRNA levels in breast cancer patients of different obesity grades. MATERIALS AND METHODS: In this case-control study, 65 breast cancer patients participated. Expression of tissues hTERT mRNA was carried out by real-time reverse transcription polymerase chain reaction. Leptin concentrations were measured by enzyme-linked immunoassay. RESULTS: Twelve patients (18.46%) were hTERT negative and 53(81.54%) were positive. hTERT mRNA levels were associated with BMI but not with waist circumference (WC) (r = 0.219, P = 0.22) and waist to hip ratio (WHR) (r = 0.212, P = 0.237). Leptin level and hTERT mRNA levels (r = 0.484, P = 0.008) were correlated as well as BMI and hTERT expression. CONCLUSIONS: This study has shown a correlation between leptin levels and hTERT expression. These findings may clarify the role of leptin in breast carcinogenesis, and hence obesity could be responsible for increased incidences in breast cancer as well as its progression via enhanced production of leptin.

Combined hepatic lipase -514C/T and cholesteryl ester transfer protein I405V polymorphisms are associated with the risk of coronary artery disease.

Hepatic lipase (LIPC) and cholesteryl ester transfer protein (CETP) are important components of high-density lipoprotein (HDL) metabolism and reverse cholesterol transport. Therefore, their genes are promising candidate genes for cardiovascular disease. The aim of the present study was to investigate whether combined LIPC -514C/T and CETP I405V polymorphisms correlate with angiographically documented coronary artery disease (CAD). Genotyping was performed in 317 patients who underwent clinically indicated coronary angiography. The patients were classified with significantly diseased arteries if one or more coronary arteries had a stenosis >50% and with minimally diseased arteries if there was no significant stenosis (<40%) in any artery. There were no significant associations of individual polymorphisms with the risk of significant CAD. In a multivariate logistic regression analysis including cardiovascular risk factors, simultaneous presence of both LIPC -514T and CETP 405V alleles was an independent predictor of significantly diseased arteries (odds ratio = 2.04; p = 0.022). This association was not significant in women with combined genotype who had the highest HDL-cholesterol. In conclusion, the combined T allele of LIPC -514C/T and V allele of CETP I405V are associated with the risk of CAD. Further, the higher HDL-cholesterol and female gender may reduce the effect of combined genotype on CAD risk.

The effect of clofibrate with phototherapy in late pre-term newborns with non-hemolytic jaundice.

BACKGROUND: Despite an understanding of the enzymatic pathways leading to bilirubin production and degradation, very few pharmacologic interventions are utilized and the mainstay of treatment remains phototherapy. AIMS: To evaluate the efficacy of clofibrate in reducing total serum bilirubin levels in late pre-term neonates with non-hemolytic jaundice. DESIGN AND SETTING: Double-blind, placebo-controlled, randomized trial; tertiary level neonatal unit. MATERIALS AND METHODS: A randomized controlled study was carried out in the neonatal ward of Children's Hospital, Tabriz, Iran, over a 1-year period. Sixty-eight healthy late pre-term infants readmitted with non-hemolytic hyperbilirubinemia were randomized to receive phototherapy and clofibrate (n= 35) or phototherapy and placebo (n= 33). STATISTICAL ANALYSIS USED: Chi-square test and independent sample 't' test. RESULTS: There were no significant differences in the weight, gender, modes of delivery and age of neonates between the two groups. Similarly the mean total serum bilirubin (TSB) level at the time of admission was not significantly different between the two groups [mean+/- SD: 19.72 +/- 1.79 (95% confidence interval: 19.12-20.54 mg/dL) vs. 20.05 +/- 2.82 (95% confidence interval, 19.54-22.04 mg/dL), P= 0.57]. The mean TSB 48 hours after phototherapy [mean+/- SD: 8.06+/- 1.34 (95% confidence interval: 7.94-10.18 mg/dL) vs.10.94 +/- 2.87 (95% confidence interval: 9.92-12.16 mg/dL), P= 0.02] and the mean duration of phototherapy [mean+/- SD: 64.32 +/- 12.48 (95% confidence interval: 60-81.6 hours) vs. 87.84 +/- 29.76 (95% confidence interval: 79.2-108 hours), P< 0.001] were significantly lower in the clofibrate-treated group. CONCLUSIONS: Clofibrate is an effective adjunctive drug in neonatal hyperbilirubinemia, which results in decreased TSB level and reduced duration of phototherapy in late pre-term newborns.

Fatty acid composition of HDL phospholipids and coronary artery disease.

BACKGROUND: The phospholipid fatty acid content of high-density lipoprotein (HDL) partially reflects that of the diet and has been reported to be associated with several important biological functions that might serve as risk markers for coronary heart disease. OBJECTIVE: To investigate whether fatty acid composition of HDL phospholipids correlates with angiographically documented coronary artery disease (CAD). METHODS: The population included 212 patients who underwent clinically indicated coronary angiography. The patients were classified with significantly diseased arteries (SDA) if one or more coronary arteries had a stenosis >50% and with minimally diseased arteries (MDA) if there was no significant stenosis (<40%) in any artery. The severity of CAD was expressed by the number of affected vessels. The fatty acid composition of HDL phospholipids was determined by gas liquid chromatography. Multivariate analyses were used to test the independence of associations between the presence and severity of CAD as outcome variables and fatty acid composition of HDL phospholipids. RESULTS: Patients with SDA showed significantly lower levels of linoleic acid (P = .041), eicosapentaenoic acid (EPA) (P = .027), and docosahexaenoic acid (DHA) (P = .026) than patients with MDA in univariate analyses. The association of linoleic acid (odds ratio [OR] .90, P < .05), EPA (OR, 0.41, P < .02), and DHA (OR, 0.48, P < .02) remained statistically significant in the multivariate analyses. The content of EPA (ß = -0.23, P < .01) and DHA (ß = -0.17, P < .05) remained inversely significantly associated with the severity of CAD. CONCLUSIONS: This study shows that polyunsaturated fatty acids, including EPA and DHA content of HDL particles, are independently associated with the presence and severity of angiographically documented CAD.