The Role of Stearoyl-coenzyme A Desaturase 1 in Liver Development, Function, and Pathogenesis

Stearoyl-coenzyme A desaturase 1 (SCD1) is a microsomal enzyme that controls fatty acid metabolism and is highly expressed in hepatocytes. SCD1 may play a key role in liver development and hepatic lipid homeostasis through promoting monounsaturated protein acylation and converting lipotoxic saturated fatty acids into monounsaturated fatty acids. Imbalanced activity of SCD1 has been implicated in fatty liver induction, inflammation and stress. In this review, the role of SCD1 in hepatic development, function and pathogenesis is discussed. Additionally, emerging novel therapeutic agents targeting SCD1 for the treatment of liver disorders are presented

Correlation of secretory phospholipase-A2 activity and fatty acids in cerebrospinal fluid with liver enzymes tests

Introduction: The aim was to determine whether secretory phospholipase-A2 (sPLA2) activity and fatty acids in cerebrospinal fluid (CSF) are correlated with liver enzymes tests. Methods: CSF and serum samples were collected from 49 patients (age 18-65) as part of routine diagnostic testing. Along with serum liver enzymes aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP), the fatty acid composition of CSF was measured by gas liquid chromatography. CSF enzyme activities of sPLA2 were measured using the standard assay with diheptanoyl thio-phosphatidylcholin as substrate. Results: The saturated fatty acids (SFAs) including palmitic acid and stearic acid were positively, and the unsaturated fatty acids including oleic acid and linoleic acid were negatively correlated with liver enzymes tests. In regression analysis with adjustment for body mass index (BMI), the elevated liver enzymes tests were positively associated with activity of sPLA2 (β > 0.31, P 0.38, P < 0.010) and negatively with total monounsaturated fatty acids (MUFAs) (β < -0.40, P < 0.001) contents of CSF. Conclusion: CSF activity of sPLA2 and fatty acids may be linked to peripheral markers of liver function, suggesting an indirect impact of central fatty acids on hepatocytes function and metabolism

Correlation between PPARγ protein expression level in granulosa cells and pregnancy rate in IVF program

Background: Peroxisome proliferative-activated receptors (PPARs) are nuclear receptors that involved in cellular lipid metabolism and differentiation. The subtype γ of the PPAR family (PPARγ) plays important roles in physiologic functions of ovaries. Objective: To determine correlation between PPARγ protein level in granulosa cells and pregnancy rate in women undergoing in-vitro fertilization (IVF) treatment. Materials and Methods: In this cross-sectional study, twenty-five samples of granulosa cells were collected from women referred to an IVF treatment center. PPARγ protein expression level in granulosa cells was determined in comparison with β-actin level as control gene with Western blot test. Laboratory pregnancy was determined by a rise in blood β-hCG level fourteen days after embryo transfer. Correlation analyses were used to test for associations between the oocytes and pregnancy occurrence as outcome variables and PPARγ protein expression level. Results: Correlation analysis indicated that there was no significant relationship between granulosa cells PPARγ protein level with IVF parameters including number of matured oocytes and the ratio of fertilized to matured oocytes. Comparison of granulosa cells PPARγ protein level with positive and negative laboratory pregnancy revealed also no significant relationship. Conclusion: According to the results of this study, PPARγ protein level in granulosa cells could not be directly correlated to the success rate of IVF

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

Fatty acids composition of aorta and saphenous vein tissues in patients with coronary artery diseases

Introduction: Considering importance of fatty acids in developing coronary artery disease (CAD) and lack of information about saphenous vein which is commonly used as coronary arterial bypass, in this study we investigated differences in fatty acids composition between saphenous vein and aorta tissues in patients with CAD. Methods: Biopsy samples of aortic tissues and saphenous veins as well as blood samples were obtained form 42 patients with CAD. Fatty acids composition of the tissues was determined using gas chromatography and also serum lipid profile was evaluated by commercial kits. Results: Levels of palmitic acid (16:0) were significantly higher in aorta in compared with saphenous (P < 0.001). Also levels of most unsaturated fatty acids (16:1, 18:1n-9, 18:1t, 18:2t, 18:3 n‐9 and 22:3n-3) were statistically higher in saphenous tissue than aorta tissue (P < 0.05). Mean levels of linoleic acid (18:2 n‐6) was higher in aorta tissue in comparison with saphenous tissue (P = 0.01). We observed positive correlations between serum levels of LDL-C with elaidic acid and linoleic acid levels in saphenous. Evaluation of aorta tissue fatty acids revealed that palmitoleic acid (16:1) had positive and arachidonic and linoleic acids had negative correlations with serum HDL-C levels. Conclusion: Our results revealed difference between fatty acids composition of aorta and saphenous vein tissues and existence of correlations between the fatty acids levels with serum lipid profile. The saphenous vein had higher poly-unsaturated fatty acids in compared to aorta tissue and thus this vein is not at risk of atherosclerosis and can be used as coronary arterial bypass

Correlation between the level of cholesteryl ester transfer protein in follicular fluid with fertilization rates in IVF/ICSI cycles

Background: Follicular fluid (FF) plays an important role in oocytes and embryo development, which may contribute to IVF/ICSI success rate. Objective: The aim of this study was to investigate the correlation between cholesteryl ester transfer protein (CETP) level in FF and the success rate of IVF/ICSI. Materials and Methods: In a cross-sectional study, FF samples, FF samples were obtained from 100 patients referred to Tabriz Alzahra Hospital. Seventy-nine subjects underwent IVF and the remaining 21 underwent ICSI. The levels of high-density lipoprotein cholesterol (HDL-C), apolipoprotein A-I and CETP were measured using enzymatic, turbidometric and ELISA methods respectively. Results: Analysis of the subgroups with different levels of CETP showed a significant lower level of CETP in the subgroup with the lowest number of mature oocytes (p<0.05). The level of CETP was also considerably lower (18%, p=0.05) in subjects with<50% oocytes fertilization ratio than subjects with >70% of this ratio. Conclusion: While no association was found for pregnancy, the amount of CETP in FF was associated positively to the maturity and the percentage of oocyte fertilization

The role of cholesterol-enriched diet and paraoxonase 1 inhibition in atherosclerosis progression

Introduction: Atherosclerosis could be deemed as a chronic, progressive, and inflammatory disease. It has been well-documented that high-density lipoprotein (HDL) can reduce the risk of the atherosclerosis occurrence through exerting some anti-atherogenic mechanisms. In recent years, the strong evidence has suggested that paraoxonase 1 (PON1) may contribute to antioxidant properties of HDL. In the present study, the impact of a diet enriched with cholesterol and also the PON1 inhibition on atheroma formation and lipid profile has been investigated. Methods: In this study, 24 New Zealand rabbits were randomly assigned to three groups receiving standard diet, atherogenic diet, and atherogenic diet plus once daily intramuscular injection of nandrolone decanoate as the PON1 inhibitor. Triglyceride, cholesterol, HDL, and low-density lipoprotein (LDL) were determined and both cholesterol accumulation in aorta and fatty streak formation were evaluated. Results: The comparison of the results in three groups reveals that cholesterol level in the group received cholesterol-enriched diet plus once daily injection of PON1 inhibitor was higher than the groups received standard diet or atherogenic diet without PON1 inhibitor (P < 0.05). Furthermore, the percentage of atheroma with type-I lesions was equal to 75% compared with the group received atherogenic diet plus nandrolone at 30%. Additionally, the differences in fatty streak formation in aorta, as well as the right and left coronary arteries in three groups given show that the difference between groups receiving atherogenic diet and standard diet was significantly lower (P < 0.05) than the difference between groups receiving atherogenic diet plus PON1 inhibitor and standard diet. Conclusion: It can be concluded that lack of paraoxanase1 or even reduced the activity of this enzyme could accelerate the progression of fatty streak lesions toward advanced atherosclerotic lesions