Altered kidney CYP2C and cyclooxygenase-2 levels are associated with obesity-related albuminuria. Obes Res 2004 Aug;12(8):1278-89
Date
09/02/2004Pubmed ID
15340111DOI
10.1038/oby.2004.162Scopus ID
2-s2.0-6344282521 (requires institutional sign-in at Scopus site) 49 CitationsAbstract
OBJECTIVE: To determine cytochrome P450 (CYP450) and cyclooxygenase (COX) expression and metabolite regulation and renal damage in the early stages of obesity-related hypertension and diabetes.
RESEARCH METHODS AND PROCEDURES: Obese and lean Zucker rats at 10 to 12 weeks of age were studied. Blood pressure was measured in the conscious state using radiotelemetry. Blood glucose levels and body weight were measured periodically. Protein expression of CYP450 and COX enzymes in the kidney cortex, renal microvessels, and glomeruli was studied. The levels of CYP450 and COX metabolites in urine were measured, and urinary albumin excretion, an indicator of kidney damage, was measured.
RESULTS: Body weight and blood glucose averaged 432 +/- 20 grams and 105 +/- 5 mg/dl, respectively, in obese Zucker rats as compared with 320 +/- 8 grams and 91 +/- 5 mg/dl, respectively, in age-matched 10- to 12-week-old lean Zucker rats. Renal microvascular CYP4A and COX-2 protein levels were increased 2.3- and 17.0-fold, respectively, in obese Zucker rats. The protein expression of CYP2C11 and CYP2C23 was decreased 2.0-fold in renal microvessels isolated from obese Zucker rats when compared with lean Zucker rats. The urinary excretion rate of thromboxane B(2) was increased significantly in obese Zucker as compared with lean Zucker rats (22.0 +/- 1.8 vs. 13.4 +/- 1.0 ng/d). Urinary albumin excretion, an index of kidney damage, was increased in the obese Zucker rat at this early age.
DISCUSSION: These results suggest that increased CYP4A and COX-2 protein levels and decreased CYP2C11 and CYP2C23 protein levels occur in association with microalbuminuria during the onset of obesity-related hypertension and type 2 diabetes.
Author List
Dey A, Williams RS, Pollock DM, Stepp DW, Newman JW, Hammock BD, Imig JDMESH terms used to index this publication - Major topics in bold
AlbuminuriaAnimals
Aryl Hydrocarbon Hydroxylases
Blood Glucose
Body Weight
Cyclooxygenase 2
Cytochrome P-450 Enzyme System
Cytochrome P450 Family 2
Diabetes Mellitus, Type 2
Hypertension
Isoenzymes
Kidney
Kidney Cortex
Kidney Glomerulus
Male
Microcirculation
Obesity
Prostaglandin-Endoperoxide Synthases
Rats
Rats, Zucker
Steroid 16-alpha-Hydroxylase
Thromboxane B2