TY - JOUR
T1 - Effects of high-fat diet, angiotensinogen (agt) gene inactivation, and targeted expression to adipose tissue on lipid metabolism and renal gene expression
AU - Kim, S.
AU - Urs, S.
AU - Massiera, F.
AU - Wortman, P.
AU - Joshi, R.
AU - Heo, Y. R.
AU - Andersen, B.
AU - Kobayashi, H.
AU - Teboul, M.
AU - Ailhaud, G.
AU - Quignard-Boulangé, A.
AU - Fukamizu, A.
AU - Jones, B. H.
AU - Kim, J. H.
AU - Moustaid-Moussa, N.
PY - 2002/11
Y1 - 2002/11
N2 - 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.
AB - 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.
KW - Adipocyte
KW - Angiotensin II
KW - Gene Expression
KW - Insulin
KW - Kidney
KW - Leptin
KW - Microarray
UR - http://www.scopus.com/inward/record.url?scp=0036875667&partnerID=8YFLogxK
U2 - 10.1055/s-2002-38263
DO - 10.1055/s-2002-38263
M3 - Article
C2 - 12660889
AN - SCOPUS:0036875667
SN - 0018-5043
VL - 34
SP - 721
EP - 725
JO - Hormone and Metabolic Research
JF - Hormone and Metabolic Research
IS - 11-12
ER -