Stimulatory Effect of Leptin on Nitric Oxide Production Is Impaired in Dietary-Induced Obesity

• Published in: Obesity (Silver Spring, Md.) Md.), 2003-12, Vol.11 (12), p.1571-1580
• Main Authors: Bełtowski, Jerzy, Wójcicka, Grażyna, Jamroz, Anna
• Format: Article
• Language: English
• Subjects: Animals; Arginine - pharmacology; arterial hypertension; Blood Pressure - drug effects; cyclic GMP; Cyclic GMP - blood; Cyclic GMP - metabolism; Cyclic GMP - urine; dietary‐induced obesity; leptin; Leptin - pharmacology; Male; nitric oxide; Nitric Oxide - biosynthesis; Nitric Oxide - blood; Nitric Oxide - urine; Nitric Oxide Donors - pharmacology; Obesity - metabolism; Random Allocation; Rats; Rats, Wistar; S-Nitroso-N-Acetylpenicillamine - pharmacology
• ISSN: 1930-7381; 1071-7323; 1930-739X; 1550-8528
• DOI: 10.1038/oby.2003.209

Objective: We investigated the effect of leptin on nitric oxide production in lean and rats made obese by a high‐calorie diet. Research Methods and Procedures: The animals were placed in metabolic cages, and urine was collected in 2‐hour periods after leptin (1 mg/kg intraperintoneally) or vehicle administration. Blood was obtained 0.5, 1, 2, 4, or 6 hours after injection. Results: Leptin had no effect on systolic blood pressure in either lean or obese animals. Plasma concentration of NO metabolites (nitrites + nitrates, NOx) increased in lean rats by 31.5%, 58.0%, and 27.9% at 1, 2, and 4 hours after leptin injection, respectively. In the obese group, plasma NOx increased only at 2 hours (+36.5%). Leptin increased urinary NOx excretion by 31.8% in the first 2‐hour period after injection in lean but not in obese rats. In lean animals, leptin elevated plasma cyclic 3′, 5′‐guanosine monophosphate (cGMP) at 1, 2, and 4 hours by 35.3%, 96.3%, and 57.3%, respectively. In the obese group, plasma cGMP was higher only at 2 and 4 hours (+44.6% and +32.1%, respectively). Urinary excretion of cGMP increased in lean animals by 67.1% in the first period and by 50.4% in the second period. In the obese group, leptin induced a 53.9% increase in urinary cGMP excretion only in the first 2‐hour period. Discussion: The stimulatory effect of leptin on NO production is impaired in dietary‐induced obesity; however, leptin does not increase blood pressure in obese animals, suggesting that other NO—independent depressor mechanisms are stimulated.