Combined amylin–leptin treatment lowers blood pressure and adiposity in lean and obese rats

• Published in: International Journal of Obesity Vol. 35; no. 9; pp. 1183 - 1192
• Main Authors: Seth, R, Knight, W.D, Overton, J.M
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 01.09.2011; Nature Publishing Group UK
• Subjects: 631/136; 692/699/2743/393; 692/699/75/243; 692/700/565/238; abdominal fat; adiposity; Adiposity - drug effects; Animals; Biological and medical sciences; Blood pressure; Blood Pressure - drug effects; Body fat; Body Weight; Body Weight - drug effects; Butter; Cardiac arrhythmia; Central nervous system; Diet; Dietary Fats; Dietary Fats - pharmacology; drug effects; Drug therapy; Eating; Eating - drug effects; Energy balance; Energy Metabolism; Energy Metabolism - drug effects; Epidemiology; Food; food intake; Health aspects; Health Promotion and Disease Prevention; Heart rate; Heart Rate - drug effects; high fat diet; Internal Medicine; Islet Amyloid Polypeptide; Islet Amyloid Polypeptide - pharmacology; Leptin; Leptin - pharmacology; Male; Medical sciences; Medicine; Medicine & Public Health; Metabolic Diseases; Metabolism; Nervous system; Obesity; original-article; Oxygen consumption; pharmacology; Physiological aspects; Physiology; Prevention; Public Health; Rats; Rats, Inbred F344; Research design; Rodents; Telemetry; United States; Florida; United States > US; Norway; respiratory quotient; metabolism; energy balance; telemetry; food intake; Adipose tissue; Rat; Adiposity; Arterial pressure; Blood pressure; Nutritional status; Obesity; Range finding; Nutrition; Rodentia; Nutrition disorder; Amylin; Metabolic diseases; Adipokine; Metabolism; Energy balance; Vertebrata; Mammalia; Food intake; Animal; Leptin; Respiratory quotient; Combined treatment; Hemodynamics
• ISSN: 0307-0565; 1476-5497; 1476-5497
• DOI: 10.1038/ijo.2010.262

Objective: To examine the cardiovascular effects of combined amylin (AMN) and leptin (LEP) treatment in lean and obese rats. Research design: Rats were instrumented for telemetry and given LEP (300 micrometer kg-1 day-1), AMN (100 micrograms kg-1 day-1), AMN+LEP or vehicle (VEH; 0.9% normal saline) via a subcutaneous mini-osmotic pump for 7 days. The VEH group was subdivided into ad libitum fed and pair-fed to the amount of food AMN+LEP animals ate daily. Rats were housed in metabolic chambers for analysis of cardiovascular physiology and metabolism. Subjects: Male Fisher 344 × Brown Norway (FBNF1; Harlan; age=3-5 months; n=72) rats were placed on standard rodent chow (LEAN, n=41) or moderately high-fat diet (OBESE; n=31) to produce obesity. Results: AMN+LEP potently reduced food intake (LEAN: 57% OBESE: 59%) and abdominal fat mass (LEAN: 56% OBESE: 41%). Pair-fed rats displayed bradycardia and metabolic suppression. In contrast, AMN+LEP increased heart rate and oxygen consumption above levels in LEP or AMN-treated rats. LEP reduced blood pressure in both lean and obese rats but AMN had no effect. LEP-induced reductions in blood pressure were not altered by AMN+LEP treatment. Thus, AMN+LEP treatment decreased food intake, body fat and blood pressure in lean and obese rats. Conclusion: We conclude that the potent anti-adiposity actions of AMN+LEP are due in part to prevention of the bradycardia and metabolic suppression typically observed with negative energy balance. Furthermore, the hypotensive actions of peripheral LEP treatment are observable in spite of the potent AMN+LEP activation of anorexic and thermogenic mechanisms in the central nervous system.