Effects of irbesartan on the growth and differentiation of adipocytes in obese zucker rats.
OBJECTIVE
The aim of this study was to evaluate the effects of the selective angiotensin receptor 1 antagonist irbesartan on the growth and differentiation of the adipocytes in obese Zucker fa/fa rats.


METHODS
Obese Zucker fa/fa rats were treated by oral route for 3 weeks with irbesartan at doses of 3-10-30 mg/kg per day. The adipocyte differentiation was evaluated by analyzing tissue samples of white (retroperitoneal) or brown (interscapular) adipose tissue for the presence of peroxisome proliferator activated receptor gamma, leptin, and the activity of glycerol-3-phosphate dehydrogenase.


RESULTS
This study showed that the treatment of obese Zucker fa/fa with irbesartan effectively reduced the differentiation of adipocytes within brown (interscapular) and white (retroperitoneal) adipose tissue. In fact, irbesartan significantly (p < 0.01) and dose-dependently reduced the tissue levels of leptin, peroxisome proliferator activated receptor gamma, and the activity of the enzyme glycerol-3-phoshate dehydrogenase accepted markers of adipocyte differentiation. None of the tested doses of irbesartan affected these markers in non-obese rats.


CONCLUSIONS
The antagonism of the angiotensin receptor 1 receptors with irbesartan reduces the adipogenic activity of angiotensin II in obese Zucker rats, with the endpoint being reduction of the growth and differentiation of the adipocytes within the adipose tissue.
Di Filippo
Clara
C
Department of Experimental Medicine, Section of Pharmacology, Second University of Naples, Via Costantinopoli 16, Italy.
Lampa
Enrico
E
Tufariello
Elisabetta
E
Petronella
Pasquale
P
Freda
Fulvio
F
Capuano
Annalisa
A
D'Amico
Michele
M
D017667:Adipocytes / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology*; D000273:Adipose Tissue / Q000737:chemistry / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D005993:Glycerolphosphate Dehydrogenase / Q000378:metabolism; D007150:Immunohistochemistry; D000077405:Irbesartan; D020738:Leptin / Q000032:analysis / Q000378:metabolism; D009765:Obesity / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D047495:PPAR gamma / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology; D044139:Receptor, Angiotensin, Type 2 / Q000502:physiology; D013777:Tetrazoles / Q000494:pharmacology*
D047228:Angiotensin II Type 1 Receptor Blockers; D001713:Biphenyl Compounds; D020738:Leptin; D047495:PPAR gamma; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013777:Tetrazoles; D005993:Glycerolphosphate Dehydrogenase; D000077405:Irbesartan