Effects of High-Fat Diet, Angiotensinogen (agt) Gene Inactivation, and Targeted Expression to Adipose Tissue on Lipid Metabolism and Renal Gene Expression

S. Kim; S. Urs; F. Massiera; P. Wortmann; R. Joshi; Y.-R. Heo; B. Andersen; H. Kobayashi; M. Teboul; G. Ailhaud; A. Quignard-Boulangé; A. Fukamizu; B. H. Jones; J. H. Kim; N. Moustaid-Moussa

doi:10.1055/s-2002-38263

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2002; 34(11/12): 721-725
DOI: 10.1055/s-2002-38263

Original Basic

Effects of High-Fat Diet, Angiotensinogen (agt) Gene Inactivation, and Targeted Expression to Adipose Tissue on Lipid Metabolism and Renal Gene Expression

S. Kim ¹ , S. Urs ¹ , F. Massiera ² , P. Wortmann ¹ , R. Joshi ¹ , Y.-R. Heo ¹ , B. Andersen ¹ , H. Kobayashi ¹ , M. Teboul ² , G. Ailhaud ² , A. Quignard-Boulangé ³ , A. Fukamizu ⁵ , B. H. Jones ⁴ , J. H. Kim ¹ , N. Moustaid-Moussa ¹

¹ University of Tennessee, Department of Nutrition and Agricultural Experiment Station, Knoxville, TN, USA
² CNRS 6543, Centre de Biochimie, Nice, France
³ INSERM U-465, Paris, France
⁴ Life Sciences Division, Oak Ridge National Laboratory, Oak Ridge, TN, USA
⁵ University of Tsukuba, Japan

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

Full Text

References

1 Kim S, Moustaid-Moussa N. Secretory, endocrine and autocrine/paracrine function of the adipocyte. J Nutr. 2000; 130 3110S-3115S
2 Havel P J. Role of adipose tissue in body-weight regulation: mechanisms regulating leptin production and energy balance. Proc Nutr Soc. 2000; 59 359-371
3 Ahima R S, Flier J S. Adipose tissue as an endocrine organ. Trends Endocrinol Metab. 2000; 11 327-332
4 Schling P, Mallow H, Trindl A, Löffler G. Evidence for a local rennin-angiotensin system in primary cultured human preadipocytes. Int J Obes Relat Metab Disord. 1999; 23 336-341
5 Engeli S, Gorzelniak K, Kreutz R, Runkel N, Distler A, Sharma A M. Co-expression of rennin-angiotensin system genes in human adipose tissue. J Hypertens. 1999; 17 555-560
6 Saye J A, Cassis L A, Sturgill T W, Lynch K R, Peach M J. Angiotensinogen gene expression in 3T3-L1 cells. Am J Physiol. 1989; 256 C448-C451
7 Frederich R C, Kahn B B, Peach M J, Flier J S. Tissue-specific nutritional regulation of angiotensinogen in adipose tissue. Hypertension. 1992; 19 339-344
8 Jones B H, Standridge M K, Taylor J W, Moustaid N. Angiotensinogen gene expression in adipose tissue: analysis of obese models and hormonal and nutritional control. Am J Physiol. 1997; 273 R236-R242
9 Kim S, Dugail I, Standridge M, Claycombe K, Chun J, Moustaid-Moussa N. Angiotensin II-responsive element is the insulin-responsive element in the adipocyte fatty acid synthase gene: role of adipocyte determination and differentiation factor 1/sterol-regulatory-element-binding protein 1c. Biochem J. 2001; 357 899-904
10 Walker W G, Whelton P K, Saito H, Russell R P, Hermann J. Relation between blood pressure and renin, renin substrate, angiotensin II, aldosterone and urinary sodium and potassium in 574 ambulatory subjects. Hypertension. 1979; 1 287-291
11 Jeunemaitre X, Soubrier F, Kotelevtsev Y V, Lifton R P, Williams C S, Charru A, Hunt S C, Hopkins P N, Williams R R, Lalouel J M. Molecular basis of human hypertension: role of angiotensinogen. Cell. 1992; 71 169-180
12 Caulfield M, Lavender P, Newell-Price J, Kamder S, Farrall M, Clark A J. Angiotensinogen in human essential hypertension. Hypertension. 1996; 28 1123-1125
13 Hegel R A, Brunt H, Connelly P W. Genetics variation on chromosome1 associated with variation in body fat distribution in man. Circulation. 1995; 92 1089-1093
14 Kim H S, Krege J H, Kluckman K D, Hangaman J R, Hodgin J B, Best C F, Jennettee J C, Coffman T M, Maceda N, Smithies O. Genetics control of blood pressure and the angiotensinogen locus. Proc Natl Acad Sci USA. 1995; 92 2735-2739
15 Schorr U, Blaschke K, Turan S, Distler A, Sharma A M. Relationship between angiotensionogen, leptin and blood pressure levels in young normotensive men. J Hypertens. 1998; 16 1475-1480
16 Massiera F, Bloch-Faura M, Ceiler D, Murakami K, Fukamizu A, Gasc J M, Quignard-Boulange A, Negrel R, Ailhaud G, Seydoux J, Meneton P, Teboul M. Adipose angiotensinogen is involved in adipose tissue growth and blood pressure regulation. FASEB. 2001; 15 2727-2729
17 Massiera F, Seydoux J, Geloen A, Quignard-Boulange A, Turban S, Saint-Marc P, Fukamizu A, Negrel R, Alihaud G, Teboul M. Angiotensinogen-deficient mice exhibit impairment of diet-induced weight gain with alterations in adipose tissue development and locomotor activity. Endocrinology. 2001; 142 5220-5225
18 Tanimoto K, Sugiyama F, Goto Y, Ishida J, Takimoto E, Yagami K, Fukamizu A, Murakami K. Angiotensinogen-deficient mice with hypotension. J Biol Chem. 1994; 269 31 334-31 337
19 Jones B H, Kim J H, Zemel M B, Wotychik R P, Michaud E J, Wilkison W O, Moustiad-Moussa N. Upregulation of adipocyte metabolism by agouti protein: possible paracrine actions in yellow mouse obesity. Am J Physiol. 1996; 270 192-196
20 Ahima R S, Flier J S. Leptin. Annu Rev Physiol. 2000; 62 413-437
21 Schwartz M W, Woods S C, Porte D , Seeley R J, Baskin D G. Central nervous system control of food intake. Nature. 2000; 404 661-671
22 Simon D B, Lifton R P. Mutations in Na(K)Cl transporters in Gitelman’s and Bartter’s syndromes. Curr Opin Cell Biol. 1998; 10 450-454
23 Simon D B, Karet F E, Hamdan J M, Dipietro A, Sanjad S A, Lifton R P. Bartter’s syndrome, hypokalaemic alkalosis with hypercalciuria, is caused by mutations in the Na-K-2Cl cotransporter NKCC2. Nat Genet. 1996; 13 183-188
24 Simon D B, Karet F E, Rodriguez-Soriano J, Hamdan J H, Dipietro A, Trachtman H, Sanjad S A, Lifton R P. Genetic heterogeneity of Bartter’s syndrome revealed by mutations in the K⁺ channel, ROMK. Nat Genet. 1996; 14 152-156
25 Simon D B, Bindra R S, Mansfield T A, Nelson-Williams C, Mendonca E, Stone R, Schurman S, Nayir A, Alpay H, Bakkaloglu A, Rodriguez-Soriano J, Morales J M, Sanjad S A, Taylor C M, Pilz D, Brem A, Trachtman H, Griswold W, Richard G A, John E, Lifton R P. Mutations in the chloride channel gene, CLCNKB, cause Bartter’s syndrome type III. Nat Genet. 1997; 17 171-178
26 Horicuchi M. Angiotensin type II receptor dephosphorylates Bcl-2 by activating mitogen-activated protein kinase phosphatase-1 and induces apoptosis. J Biol Chem. 1996; 272 19 022-19 026
27 Darimont C, Vassaux G, Ailhaud G, Negrel R. Differentiation of preadipose cells: paracrine role of prostacyclin upon stimulation of adipose cells by angiotensin-II. Endocrinology. 1994; 135 2030-2036
28 Jones B H, Standridge M K, Moustaid-Moussa N. Angiotensin II increases lipogenesis in 3T3-L1 and human adipose cell. Endocrinology. 1997; 138 1512-1519
29 Crandall D L, Armellino D C, Busler D E, McHendry-Rinde B, Kral J G. Angiotension II receptors in human preadipocytes: role in cell cycle regulation. Endocrinology. 1999; 140 154-158
30 Schmidt M, Renner C, Löffler G. Induction of estrogen biosynthesis in human adipose tissue stromal cells by angiotensin II. Int J Obes Relat Metab Disord. 1998; 22 Suppl. 3 S14 (abstract)
31 Matsumoto A M, Marck B T, Gruenewald D A, Wolden-Hanson T, Naai M A. Aging and the neuroendocrine regulation of reproduction and body weight. Exp Gerontol. 2000; 35 1251-1265
32 Engeli S, Sharma A M. Role of adipose tissue for cardiovascular-renal regulation in health and disease. Horm Metab Res. 2000; 32 485-499
33 Shurk T, Lee Y-M, Röhrig K, Hauner H. Effect of angiotensin peptides on PAI-1 expression and production in human adipocytes. Horm Metab Res. 2001; 33 196-200
34 Mallow H, Trindl A, Löffler G. Production of angiotensin II receptors type one (AT1) and type two (AT2) during the differentiation of 3T3-L1 preadipocytes. Horm Metab Res. 2000; 32 500-503

N. Moustaid-Moussa, Ph.D.

University of Tennessee · Nutrition Department and Agricultural Experiment Station

229 Jessie Harris Building · University of Tennessee · Knoxville · TN 37996-1900 · USA

Phone: + 1 (865) 974-6255

Fax: + 1 (865) 974-3491

Email: moustaid@utk.edu