AT2 Receptor Deficiency Attenuates Adipocyte Differentiation and Decreases Adipocyte Number in Atherosclerotic Mice

• Published in: American journal of hypertension 2009-07, Vol.22 (7), p.784-791
• Main Authors: Iwai, Masaru, Tomono, Yumiko, Inaba, Shinji, Kanno, Harumi, Senba, Izumi, Mogi, Masaki, Horiuchi, Masatsugu
• Format: Article
• Language: English
• Subjects: Adipocytes - physiology; Adipose Tissue - drug effects; Adipose Tissue - pathology; Angiotensin II Type 1 Receptor Blockers - pharmacology; Angiotensin II Type 2 Receptor Blockers; Animals; Apolipoproteins E - genetics; Arterial hypertension. Arterial hypotension; Atherosclerosis - pathology; Atherosclerosis - physiopathology; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cell Count; Cell Differentiation - physiology; Cholesterol, Dietary - administration & dosage; Clinical manifestations. Epidemiology. Investigative techniques. Etiology; Insulin Receptor Substrate Proteins - metabolism; Male; Medical sciences; Mice; Mice, Knockout; NADPH Oxidases - metabolism; Receptor, Angiotensin, Type 2 - deficiency; Receptor, Angiotensin, Type 2 - physiology; Tetrazoles - pharmacology; Valine - analogs & derivatives; Valine - pharmacology; Valsartan
• ISSN: 0895-7061; 1941-7225; 1879-1905
• DOI: 10.1038/ajh.2009.85

Background Previous reports indicated that blockade of AT1 receptor stimulation attenuated adipocyte dysfunction. However, the effects of AT2 receptor stimulation on adipose tissue were not yet clear. In the present study, we examined the adipose tissue dysfunction in atherosclerotic apolipoprotein E knockout (ApoEKO) mice with AT2 receptor deficiency. Methods Male ApoEKO and AT2 receptor/ApoE knockout (AT2/ApoEKO) mice at 6 weeks of age were treated with a normal diet or a high-cholesterol diet (HCD: 1.25% cholesterol). Markers for adipocyte differentiation and inflammation in adipose tissue were assayed with real-time reverse-transcription-PCR and western blot. Results Compared with ApoEKO mice, AT2/ApoEKO mice with a normal diet showed only a decrease in expression of adiponectin and CCAAT/enhancer binding protein δ (C/EBPδ) in epididymal adipose tissue without changes in body weight, adipose tissue weight, and adipocyte number even at 6 months of age. After HCD for 4 weeks, the weight of both epididymal and retroperitoneal adipose tissue in AT2/ApoEKO mice was greater than that in ApoEKO mice without a change in body weight. Plasma concentrations of cholesterol and fatty acids were higher in AT2/ApoEKO mice than in ApoEKO mice. In adipose tissue of AT2/ApoEKO mice, the adipocyte number was decreased and the expression of peroxisome proliferator–activated receptor γ (PPARγ), C/EBPα, and aP2 was lower than that in ApoEKO mice, in association with an increase in nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity. Conclusions These results suggest that AT2 receptor stimulation in adipose tissue is involved in the improvement of adipocyte differentiation and adipose tissue dysfunction in atherosclerotic model.