Pioglitazone ameliorates high fat diet-induced hypertension and induces catechol o-methyl transferase expression in rats.

Our study aimed to investigate the effect of pioglitazone (PIO) on the obesity-associated metabolic effects and whether this effect is associated with modulation of catechol O-methyl transferase (COMT) expression in the high fat diet (HFD) induced obese rats. Male Wistar rats fed HFD were used to evaluate the effect of PIO on obesity-associated hypertension and the expression of COMT. The HFD-induced obesity was confirmed by the change in body weights, the fasting serum insulin (FSI) which assessed by ELISA, homeostasis model assessment - insulin resistance (HOMA-IR), fasting blood glucose (FBG), oral glucose tolerance test (OGTT) and lipid profile which were determined by colorimetric methods. Plasma epinephrine (EP) and norepinephrine (NE) were determined by ELISA and the systolic blood pressure (SBP) was recorded using the tail-cuff method. COMT expression was assessed by quantitative real time-polymerase chain reaction (qRT-PCR), and western blotting. The HFD-induced obesity was associated with glucose intolerance, derangement of the lipid profile, increased SBP, reduced COMT expression with a concomitant increase in plasma catecholamines. Most importantly, treatment with PIO ameliorated the HFD-induced metabolic changes, improved the lipid profile, reduced SBP, increased COMT expression, and reduced plasma catecholamines. Treatment with PIO reversed HFD-induced glucose intolerance and the associated metabolic derangement. In addition, these effects of PIO were associated with up-regulating COMT expression with a subsequent reduction in plasma catecholamines levels.

Potential role of circulating microRNAs (486-5p, 497, 509-5p and 605) in metabolic syndrome Egyptian male patients.

Objective: This study aims to evaluate the expression pattern of circulating microRNAs (miR)-486-5p, miR-497, miR-509-5p, and miR-605 in the serum of metabolic syndrome (MetS) Egyptian male patients. Methods: In this study, the circulating miR-486-5p, miR-497, miR509-5p, and miR-605 were amplified and quantitatively detected by quantitative real-time polymerase chain reaction in sera of 55 MetS male patients in comparison to 20 male controls. The level of fasting plasma glucose and triacylglycerol (TAG) were measured using calorimetric assay. Blood pressure was measured using mercuric sphygmomanometer. Anthropometric measurements were done to each individual. Furthermore, MetS patients were defined according to the criteria proposed by the American Heart Association and divided into three groups according to MetS index. Results: The study was performed on three groups and a control group defined as follows: group 1: 15 MetS patients who fulfilled all diagnostic criteria of MetS; group 2: 20 MetS patients with normal blood pressure; group 3: 20 MetS patients with normal TAG levels.The levels of miRs are expressed as [median (IQR)]. miR-486-5-p and miR-497 expression were elevated in group 1 [31.9(49), p˂0.0001; 73.1(42.5), p˂0.0001], group 2 [36.4(15.7), p˂0.0001; 68.3(54.8), p˂0.0001], and group (3) [10.8(18.9), p=0.0014; 27.5(39.7), p=0.0012]. MiR-509-5p was elevated in groups 1 and 2 [501(468), p=0.0001], [309(436), p=0.0006], respectively, while normally expressed in group 3 [0.93(0.077), p=0.0001]. miR-605 was elevated in groups 1 and 3 [25.4(20.0), p=0.0018], [54.8(65.8), p˂0.0001], while normally expressed in group 2 [0.84(0.67), p˂0.0001]. Conclusion: miRs (486-5p, 497, 509-5p, and 605) serum levels were higher in MetS patients than in healthy control subjects; therefore, these serum miRs can serve as early biomarkers and can be used to follow-up the prognosis of MetS.