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

• Published in: European journal of pharmacology Vol. 885; p. 173383
• Main Authors: Hegazy, Maghawry, El-Shafey, Mostafa, Abulsoud, Ahmed Ibrahim, Elsadek, Bakheet E.M., Abd Elaziz, Adel I., Salama, Salama Abdou
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.10.2020
• Subjects: Animals; Antihypertensive Agents - therapeutic use; Blood Glucose - metabolism; Body Weight; Catechol O-Methyltransferase - biosynthesis; Catechol O-Methyltransferase - genetics; COMT; Diet, High-Fat; Epinephrine - blood; Glucose Tolerance Test; Hypertension; Hypertension - drug therapy; Hypertension - etiology; Insulin - blood; Insulin Resistance; Lipid Metabolism - drug effects; Male; Norepinephrine - blood; Obesity; Obesity - metabolism; Pioglitazone; Pioglitazone - therapeutic use; Rats; Rats, Wistar; Hypertension; Obesity; Insulin resistance; COMT; Pioglitazone
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2020.173383

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.