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Tissue-specific effects of valsartan on rstn and fiaf gene expression in the ob/ob mouse
S A Imran1, R E Brown, M Wilkinson
1Division of Endocrinology, Dalhousie University, 1278 Tower Road, Halifax, NS, Canada. ali.imran@cdha.nshealth.ca
Abstract:
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.
Insights
Valsartan treatment normalized fasting-induced adipose factor (fiaf) gene expression in subcutaneous fat of obese mice. Resistin (rstn) gene expression was reduced in visceral fat but unaffected by valsartan.
Area of Science:
- Endocrinology
- Molecular Biology
- Pharmacology
Background:
- The renin-angiotensin system (RAS) is a novel target in diabetes research.
- Angiotensin receptor blockers (ARBs), like valsartan, may influence adipose tissue function.
- Adipokines, such as resistin (rstn) and fasting-induced adipose factor (fiaf), play roles in metabolic regulation.
Purpose of the Study:
- To investigate the effect of valsartan on rstn and fiaf gene expression in obese and diabetic ob/ob mice.
- To determine if valsartan influences adipokine expression in various tissues, including adipose tissue, pituitary, cerebral cortex, and hypothalamus.
Main Methods:
- Utilized obese and diabetic ob/ob mouse models.
- Quantified mRNA levels of rstn and fiaf in visceral fat, subcutaneous fat, pituitary, cerebral cortex, and hypothalamus.
- Administered valsartan treatment for 2 weeks to assess its impact on gene expression.
Main Results:
- Fiaf gene expression was elevated 2-4 fold in visceral and subcutaneous fat of ob/ob mice compared to lean controls.
- Valsartan treatment normalized fiaf mRNA levels in subcutaneous fat, but not visceral fat, of ob/ob mice.
- Fiaf expression was reduced in the hypothalamus of ob/ob mice, independent of valsartan.
- Rstn expression was significantly reduced in visceral fat of ob/ob mice, but unaffected by valsartan.
- Rstn expression remained unchanged in other examined tissues regardless of valsartan treatment.
Conclusions:
- Valsartan demonstrates tissue-specific effects on adipokine gene expression in obese and diabetic mice.
- The normalization of fiaf in subcutaneous fat suggests a potential therapeutic role for valsartan in modulating adipose tissue dysfunction.
- Further research is warranted to elucidate the precise mechanisms underlying valsartan's influence on adipokines and its implications for diabetes treatment.
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