International Mammalian Genome Society

The 16th International Mouse Genome Conference (2002)


POSTER 155 - EFFECT OF ANGIOTENSINOGEN (AGT) GENE INACTIVATION AND OVEREXPRESSION ON ADIPOCYTE METABOLISM AND RENAL GENE EXPRESSION

S Urs
University of Tennessee

1) Kim S, 2) Massiera F, 1) Joshi R, 1) Andersen B, 1) Derfus M, 2) Teboul M, 2) Ailhaud G, 3) Jones B, 1) Moustaid-Moussa N
1) University of Tennessee, 2) CNRS, 3) Oak Ridge National Labs

Adipose tissue expresses high levels of angiotensinogen (agt), the only known precursor of angiotensin II (Ang II) and we have shown that this hormone plays a paracrine role in regulation of adipocyte metabolism and gene expression. To address the role of agt in regulating lipid metabolism in vivo, we studied the effects of low and high fat diets on adult agt knockout (agt -/-) compared to wild type (wt) mice. Since recent studies by Massiera et al., 2001, demonstrated that reexpression of agt in adipose tissue of agt-/- mice normalized adiposity, blood pressure and kidney abnormalities associated with agt inactivation, we used microarray analysis to investigate changes in gene expression profile in kidneys of agt-/- vs. agt-/- which reexpress agt in adipose tissue.  Although body weight, adiposity and insulin level were significantly decreased (p<0.01) in agt-/- mice fed a chow diet compared to wt mice, circulating leptin levels were comparable. Compared with wt mice fed a high fat diet, agt-/- mice on a low fat diet exhibited significantly lower body weight (p< 0.01), lower adiposity  (p<0.01) and lower leptin and insulin levels (p<0.01).  Preliminary findings indicate that in comparison with agt -/-, re-expression of agt in adipose tissue significantly alters gene expression profile in kidney of these mice.  We conclude that adipocyte-derived Ang II not only regulates adipose tissue metabolism in a paracrine manner but also plays an endocrine role by regulating blood pressure and kidney homeostasis.


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