Aliskiren reduces body-weight gain, adiposity and plasma leptin during diet-induced obesity.
OBJECTIVE
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.


METHODS
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.


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
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.
Stucchi
Paula
P
Instituto Pluridisciplinar and Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain.
Cano
Victoria
V
Ruiz-Gayo
Mariano
M
Fernández-Alfonso
María S
MS
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D050154:Adiposity / Q000187:drug effects*; D000577:Amides / Q000494:pharmacology*; D000818:Animals; D004041:Dietary Fats / Q000008:administration & dosage*; D004435:Eating / Q000187:drug effects; D002149:Energy Intake / Q000187:drug effects; D005650:Fumarates / Q000494:pharmacology*; D020738:Leptin / Q000097:blood* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000097:blood* / Q000209:etiology / Q000503:physiopathology; D009929:Organ Size / Q000187:drug effects; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects; D015430:Weight Gain / Q000187:drug effects*; D000092502:Renin Inhibitors
D000577:Amides; D004041:Dietary Fats; D005650:Fumarates; D020738:Leptin; D012083:Renin; D000092502:Renin Inhibitors; C446481:aliskiren
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