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Am J Physiol Endocrinol Metab (January 28, 2004). doi:10.1152/ajpendo.00551.2003
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Submitted on December 4, 2003
Accepted on January 22, 2004

Adipose Depot-Specific Modulation of Angiotensinogen Gene Expression in Diet-Induced Obesity

Kamal Rahmouni1, Allyn L. Mark1, William G. Haynes1, and Curt D. Sigmund1*

1 Hypertension Genetics SCOR, Cardiovascular Center, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, USA

* To whom correspondence should be addressed. E-mail: curt-sigmund{at}uiowa.edu.

Adipose tissue represents an important source of angiotensinogen (AGT). We investigated the effect of obesity induced by a high fat diet on the expression of mouse (mAGT) and human AGT (hAGT) genes in liver, kidney and heart and different adipose depots in normal mice (C57BL/6J), and in transgenic mice expressing the hAGT gene under the control of its own promoter. Mice were fed a high fat diet (45% kcal) or normal chow (10% kcal) for 10 and 20 weeks. The expression of mAGT and hAGT mRNA was quantified using an RNAse protection assay. Mice on the high fat diet exhibited increased weight, fat mass and plasma leptin. Expression of mAGT or hAGT genes was not affected by high fat diet in non-adipose tissues, brown adipose tissue (BAT) or subcutaneous white fat. In contrast, high fat diet increased both mAGT and hAGT gene expression in visceral adipose depots (omental, reproductive and peri-renal fat). Thus, obesity-induced by a high fat diet is associated with a tissue specific increased expression of both mouse and human AGT genes in intra-abdominal adipose tissue. Our findings also suggest that 1.2 Kb of regulatory sequences present in the hAGT transgene are sufficient to transcriptionally respond to a high fat diet in an adipose-specific and depot-specific manner.




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