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
References
+ channel, ROMK.
Nat Genet.
1996;
14
152-156
moustaid@utk.edu
