Adipose tissue-specific increase in angiotensinogen expression and secretion in the obese (fa/fa) Zucker rat.

We investigated angiotensinogen (AGT) expression in adipose tissue and liver of Zucker rats during the onset of obesity. The developmental pattern of AGT expression (protein and mRNA) in liver was similar in both genotypes. In inguinal adipose tissue, AGT cell content was similar in suckling and weaned pups in lean rats, whereas it continuously increased with age in obese rats. AGT amount in adipocytes was unaffected by the genotype until weaning. Thereafter, adipocytes from obese rats displayed a significant increase in AGT content that was strengthened with age. Compared with the cell content, the amount of secreted AGT over 24 h was higher, and a genotype effect was observed as early as 14 days of age. Using fat cell populations differing by size, we showed that this AGT oversecretion was not solely related to adipocyte hypertrophy. Our results demonstrate that the fa genotype exerts a control on the production of AGT in a tissue-specific manner, suggesting a local role of AGT in the overdevelopment of adipose tissue.

[1]  H. Vidal,et al.  Differences in mRNA expression of the proteins secreted by the adipocytes in human subcutaneous and visceral adipose tissues. , 2000, Biochimica et biophysica acta.

[2]  B. H. Jones,et al.  Angiotensin II increases lipogenesis in 3T3-L1 and human adipose cells. , 1997, Endocrinology.

[3]  F. Pi‐Sunyer,et al.  Variations of glucose metabolism by fat cells from three adipose depots of the rat. , 1982, Metabolism: clinical and experimental.

[4]  Y. Matsuzawa,et al.  Close correlation of intra-abdominal fat accumulation to hypertension in obese women. , 1990, Hypertension.

[5]  I. Dugail,et al.  Evidence for a sustained genetic effect on fat storage capacity in cultured adipose cells from Zucker rats. , 1994, The American journal of physiology.

[6]  G. Bray,et al.  Hypothalamic and genetic obesity in experimental animals: an autonomic and endocrine hypothesis. , 1979, Physiological reviews.

[7]  Portland Press Ltd Adipose-tissue-specific increase in glyceraldehyde-3-phosphate dehydrogenase activity and mRNA amounts in suckling pre-obese Zucker rats. Effect of weaning , 1989 .

[8]  J. Ménard,et al.  Characterization of precursor and secreted forms of rat angiotensinogen. , 1984, Endocrinology.

[9]  M. Digirolamo,et al.  Components of the renin-angiotensin system in adipose tissue: changes with maturation and adipose mass enlargement. , 1995, The journals of gerontology. Series A, Biological sciences and medical sciences.

[10]  P. Björntorp,et al.  Regional adipose tissue metabolism in men and postmenopausal women. , 1987, International journal of obesity.

[11]  P. Chomczyński,et al.  Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. , 1987, Analytical biochemistry.

[12]  I. Dugail,et al.  Gene expression of lipid storage-related enzymes in adipose tissue of the genetically obese Zucker rat. Co-ordinated increase in transcriptional activity and potentiation by hyperinsulinaemia. , 1992, The Biochemical journal.

[13]  J. Flier,et al.  Tissue-specific nutritional regulation of angiotensinogen in adipose tissue. , 1992, Hypertension.

[14]  G. Ailhaud,et al.  Regulation by fatty acids of angiotensinogen gene expression in preadipose cells. , 1997, The Biochemical journal.

[15]  J. Ménard,et al.  Synthesis and release of immunoreactive angiotensinogen by rat liver slices. , 1983, Endocrinology.

[16]  M. Peach,et al.  Changes in Angiotensinogen Messenger RNA in Differentiating 3T3‐F442A Adipocytes , 1990, Hypertension.

[17]  D. L. Crandall,et al.  Developmental aspects of the Adipose tissue renin‐angiotensin system: Therapeutic implications , 1994 .

[18]  A. Fukamizu,et al.  Molecular mechanism of adipogenic activation of the angiotensinogen gene. , 1994, Hypertension.

[19]  J. W. Taylor,et al.  Angiotensinogen gene expression in adipose tissue: analysis of obese models and hormonal and nutritional control. , 1997, The American journal of physiology.

[20]  J. Kral,et al.  The role of angiotensin II and its receptors in regulation of adipose tissue metabolism and cellularity. , 1995, General physiology and biophysics.

[21]  M. Phillips,et al.  Leptin receptor missense mutation in the fatty Zucker rat , 1996, Nature Genetics.

[22]  L. Tartaglia,et al.  Phenotypes of Mouse diabetes and Rat fatty Due to Mutations in the OB (Leptin) Receptor , 1996, Science.

[23]  J. Ménard,et al.  Direct radioimmunoassay of rat angiotensinogen and its application to rats in various endocrine states. , 1982, Clinical science.

[24]  T. Sturgill,et al.  Angiotensinogen gene expression in 3T3-L1 cells. , 1989, The American journal of physiology.

[25]  B. Spiegelman,et al.  Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. , 1993, Science.

[26]  P. Arner,et al.  Regional differences in the control of lipolysis in human adipose tissue. , 1979, Metabolism: clinical and experimental.

[27]  G. Ailhaud,et al.  Insulin down-regulates angiotensinogen gene expression and angiotensinogen secretion in cultured adipose cells. , 1998, Biochemical and biophysical research communications.

[28]  C. Deschepper,et al.  Rat angiotensinogen is secreted only constitutively when transfected into AtT-20 cells. , 1990, Hypertension.

[29]  C. Darimont,et al.  Differentiation of preadipose cells: paracrine role of prostacyclin upon stimulation of adipose cells by angiotensin-II. , 1994, Endocrinology.

[30]  J. Ménard,et al.  Measurement of renin activity, concentration and substrate in rat plasma by radioimmunoassay of angiotensin I. , 1972, Endocrinology.

[31]  K. Nakao,et al.  Augmented expression of obese (ob) gene during the process of obesity in genetically obese‐hyperglycemic Wistar fatty (falfa) rats , 1996, FEBS letters.

[32]  E. Planche,et al.  Onset and development of hypertriglyceridemia in the Zucker rat (fa/fa). , 1981, Metabolism: clinical and experimental.

[33]  N. Turner,et al.  Effects of Genetic Hyperinsulinaemia on Vascular Reactivity, Blood Pressure, and Renal Structure in the Zucker Rat , 1995, Journal of cardiovascular pharmacology.

[34]  E. Planche,et al.  Onset of genetic obesity in the absence of hyperphagia during the first week of life in the Zucker rat (fa/fa). , 1979, Journal of lipid research.

[35]  É. Hajduch,et al.  Fatty genotype-induced increase in GLUT4 promoter activity in transfected adipocytes: delineation of two fa-responsive regions and glucose effect. , 1995, Biochemical and biophysical research communications.

[36]  C. Susini,et al.  A Reliable Photomicrographic Method for Determining Fat Cell Size and Number: Application to dietary obesity 1 , 1977, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[37]  Y. Giudicelli,et al.  Influence of ovariectomy and regional fat distribution on the membranous transducing system controlling lipolysis in rat fat cells. , 1991, Endocrinology.