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Am J Physiol Endocrinol Metab 286: E891-E895, 2004. First published January 28, 2004; doi:10.1152/ajpendo.00551.2003
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Adipose depot-specific modulation of angiotensinogen gene expression in diet-induced obesity

Kamal Rahmouni, Allyn L. Mark, William G. Haynes, and Curt D. Sigmund

Hypertension Genetics Specialized Center of Research, Cardiovascular Center, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242

Submitted 4 December 2003 ; accepted in final form 22 January 2004

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 wk. 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 nonadipose tissues, brown adipose tissue, or subcutaneous white fat. In contrast, high-fat diet increased both mAGT and hAGT gene expression in visceral adipose depots (omental, reproductive, and perirenal 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.

renin-angiotensin system; adipocyte; hypertension


Address for reprint requests and other correspondence: C. D. Sigmund, Depts. of Internal Medicine and Physiology & Biophysics, 3181B Medical Education and Biomedical Research Facility (MEBRF), Roy J. and Lucille A. Carver College of Medicine, Univ. of Iowa, Iowa City, IA 52242 (E-mail: curt-sigmund{at}uiowa.edu).




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