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Horm Metab Res 2002; 34(11/12): 721-725
DOI: 10.1055/s-2002-38263
Original Basic
© Georg Thieme Verlag Stuttgart · New York

Effects of High-Fat Diet, Angiotensinogen (agt) Gene Inactivation, and Targeted Expression to Adipose Tissue on Lipid Metabolism and Renal Gene Expression

S.  Kim 1 , S.  Urs 1 , F.  Massiera 2 , P.  Wortmann 1 , R.  Joshi 1 , Y.-R.  Heo 1 , B.  Andersen 1 , H.  Kobayashi 1 , M.  Teboul 2 , G.  Ailhaud 2 , A.  Quignard-Boulangé 3 , A.  Fukamizu 5 , B.  H.  Jones 4 , J.  H.  Kim 1 , N.   Moustaid-Moussa 1
  • 1 University of Tennessee, Department of Nutrition and Agricultural Experiment Station, Knoxville, TN, USA
  • 2 CNRS 6543, Centre de Biochimie, Nice, France
  • 3 INSERM U-465, Paris, France
  • 4 Life Sciences Division, Oak Ridge National Laboratory, Oak Ridge, TN, USA
  • 5 University of Tsukuba, Japan
Further Information

Publication History

Received 1 October 2002

Accepted after revision 5 December 2002

Publication Date:
27 March 2003 (online)

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Abstract

To address the role of angiotensinogen (agt) in lipid metabolism and its potential endocrine effects in vivo, we studied the effects of high-fat diet (HFD) on adult, 28-week-old agt knockout (KO) mice compared to wild type (WT) mice. Recent studies (Massiera et al., 2001) have demonstrated that reexpression of agt in adipose tissue of KO mice normalized adiposity, blood pressure, and kidney abnormalities. We therefore used microarray analysis to investigate changes in gene expression profile in kidneys of KO vs. Tg-KO mice, where agt expression is restricted to adipose tissue. Body weight, adiposity and insulin levels were significantly decreased (p < 0.05) in KO mice on a chow diet (CD) compared to WT mice, while circulating leptin levels were similar. On a high-fat diet, KO mice exhibited significantly lower bodyweight (p < 0.05), adiposity (p < 0.05), leptin, and insulin levels (p < 0.05) compared to WT mice. In agreement with previously reported changes in kidney histology, agt KO mice displayed altered expressions of genes involved in blood pressure regulation and renal function, but these levels were corrected by reexpression of agt in adipose tissue. Collectively, these findings further document important endocrine roles of adipocyte agt, in part via regulation of lipid metabolism and kidney homeostasis.

Key words

Angiotensin II - Adipocyte - Kidney - Microarray - Gene Expression - Leptin - Insulin

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N. Moustaid-Moussa, Ph.D. 

University of Tennessee · Nutrition Department and Agricultural Experiment Station

229 Jessie Harris Building · University of Tennessee · Knoxville · TN 37996-1900 · USA

Phone: + 1 (865) 974-6255

Fax: + 1 (865) 974-3491

Email: moustaid@utk.edu