Tissue-specific effects of valsartan on rstn and fiaf gene expression in the ob/ob mouse.
The RAS is a novel target in the study of diabetes, and clinical trials have indicated that ARBs, such as valsartan, may exert some of their clinical effects through an influence on adipose tissue. We studied the effect of valsartan on adipokine genes resistin (rstn) and fasting-induced adipose factor (fiaf) using obese and diabetic ob/ob mice. In addition to visceral and subcutaneous fat, rstn and fiaf mRNA levels were also measured in several other tissues known to express these adipokines, including the pituitary, cerebral cortex and hypothalamus. The significant findings were that (a) fiaf gene expression was elevated two- to fourfold in visceral and subcutaneous fat from ob/ob mice, compared with lean controls; (b) the increase in fiaf mRNA in subcutaneous, but not visceral, fat from ob/ob mice was returned to lean control levels following 2 weeks of valsartan treatment; (c) fiaf expression was reduced in the hypothalamus, but not in the cortex or pituitary, of ob/ob mice; (d) rstn expression was greatly reduced in visceral fat from ob/ob mice, compared with lean controls, but this was unaffected by valsartan; and (e) rstn expression was unchanged in all other tissues from ob/ob mice, with or without valsartan treatment.
Imran
S A
SA
Division of Endocrinology, Dalhousie University, 1278 Tower Road, Halifax, NS, Canada. ali.imran@cdha.nshealth.ca
Brown
R E
RE
Wilkinson
M
M
D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins / Q000235:genetics*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003920:Diabetes Mellitus / Q000235:genetics*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D050152:Intra-Abdominal Fat / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000235:genetics*; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D052243:Resistin / Q000235:genetics*; D050151:Subcutaneous Fat / Q000187:drug effects / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology*; D013997:Time Factors; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000068756:Valsartan
D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins; D047228:Angiotensin II Type 1 Receptor Blockers; C407088:Angptl4 protein, mouse; D012333:RNA, Messenger; D052243:Resistin; C499623:Retn protein, mouse; D013777:Tetrazoles; D000068756:Valsartan; D014633:Valine