Aliskiren reduces body‐weight gain, adiposity and plasma leptin during diet‐induced obesity

• Published in: British journal of pharmacology 2009-10, Vol.158 (3), p.771-778
• Main Authors: Stucchi, Paula, Cano, Victoria, Ruiz‐Gayo, Mariano, Fernández‐Alfonso, María S
• Format: Article
• Language: English
• Subjects: adipose tissue; Adipose Tissue - drug effects; Adipose Tissue - metabolism; Adipose Tissue - physiopathology; Adiposity - drug effects; aliskiren; Amides - pharmacology; angiotensin II; Animals; Biological and medical sciences; Dietary Fats - administration & dosage; diet‐induced obesity; direct renin inhibition; Eating - drug effects; Energy Intake - drug effects; Fumarates - pharmacology; leptin; Leptin - blood; Leptin - metabolism; Male; Medical sciences; Metabolic diseases; Mice; Mice, Inbred C57BL; Obesity; Obesity - blood; Obesity - etiology; Obesity - physiopathology; Organ Size - drug effects; Pharmacology. Drug treatments; Renin - antagonists & inhibitors; Renin - blood; Renin-Angiotensin System - drug effects; renin‐angiotensin system; Research Papers; Weight Gain - drug effects
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.2009.00355.x

Background and purpose:  Overfeeding increases adipose tissue mass and leptin production and up‐regulates the renin‐angiotensin system in adipose tissue in rodents. Here, we determined the effect of chronic treatment with the renin inhibitor, aliskiren, in a model of diet‐induced obesity in mice, on: (i) body weight, adipose tissue weight and plasma leptin; (ii) food intake and caloric efficiency; and (iii) angiotensin II (Ang II) in adipose tissue. Experimental approach:  Four‐week‐old C57BL/6J mice (n= 40) received aliskiren (50 mg·kg−1·day−1; 6 weeks) by means of a subcutaneous osmotic Alzet minipump. Animals were given either a low‐fat (10% kcal from fat) or a high‐fat diet (45% kcal from fat) during this period. Food‐intake and body‐weight variation were monitored during treatment. Key results:  In addition to a decrease of plasma renin activity, aliskiren reduced body‐weight gain, adipose pads and plasma leptin concentration, independent of the diet. In adipose tissue, local concentrations of Ang II were also reduced by aliskiren. Conclusions and implications:  Aliskiren limited the gain of adiposity in young mice. This effect was not due to changes in food intake or caloric efficiency and might be related to a down‐regulation of the local renin‐angiotensin system in adipose tissue. These effects were accompanied by reduced plasma leptin levels. As Ang II favours differentiation of adipocytes, it is possible that the decreased adipose tissue was linked to changes in adipocyte size and number.