1. Effects of High-Fat Diet, Angiotensinogen (agt) Gene Inactivation, and Targeted Expression to Adipose Tissue on Lipid Metabolism and Renal Gene Expression
- Author
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J. H. Kim, Young-Ran Heo, R. Joshi, S. Urs, Florence Massiera, Suyeon Kim, Brynn H. Jones, P. Wortmann, Annie Quignard-Boulangé, H. Kobayashi, Naima Moustaid-Moussa, Gérard Ailhaud, Michèle Teboul, Akiyoshi Fukamizu, and B. Andersen
- Subjects
Leptin ,Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Clinical Biochemistry ,Angiotensinogen ,Adipose tissue ,Blood Pressure ,Mice, Transgenic ,Biology ,Kidney ,Biochemistry ,Mice ,chemistry.chemical_compound ,Endocrinology ,Adipocyte ,Internal medicine ,parasitic diseases ,medicine ,Animals ,Insulin ,Oligonucleotide Array Sequence Analysis ,Mice, Knockout ,Gene Expression Profiling ,Body Weight ,Biochemistry (medical) ,Lipid metabolism ,General Medicine ,Lipid Metabolism ,Dietary Fats ,Angiotensin II ,medicine.anatomical_structure ,Adipose Tissue ,chemistry ,Body Composition ,Homeostasis - 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.
- Published
- 2002