Effects of Angiotensin II on Adipose Conversion and Expression of Genes of the Renin-Angiotensin System in Human Preadipocytes

A complete functional renin-angiotensin system exists in human adipose tissue, but its regulation and the effects of angiotensin II on cells from this tissue are only beginning to be understood. In this study, we examined the effects of angiotensin II on changes in lipid accumulation, specific glycerol-3-phosphate dehydrogenase activity, and the expression of five genes of the renin-angiotensin system during the adipose conversion of human primary cultured preadipocytes. Angiotensin II leads to a distinct reduction in insulin-induced differentiation, but only has a marginal effect on the adipose conversion of cells stimulated with insulin, cortisol, and isobutyl methyl xanthine. During differentiation, angiotensinogen mRNA levels rise, renin mRNA levels decline, whereas renin-binding protein and angiotensin-converting enzyme levels are unaffected. Angiotensin II downregulates angiotensinogen and renin gene expression, but it does not affect renin-binding protein and angiotensin-converting enzyme levels. Angiotensin II thus prevents the development of adipocytes in contact with high insulin levels, while not inhibiting differentiation, which is further stimulated. Therefore, angiotensin II could be a protective factor against uncontrolled expansion of adipose tissue. Further studies are needed to find out whether the effects of angiotensin II on the renin-angiotensin system are direct feedback loops or secondary to changes in the differentiation program.

Key words:

Differentiation - Angiotensinogen - Renin - Renin-Binding Protein - Angiotensin-Converting Enzyme

References

• 1 Weber K T. Angiotensin II and connective tissue: homeostasis and reciprocal regulation.  Regul Pept. 1999;  82 1-17
• 2 Schling P, Mallow H, Trindl A, Löffler G. Evidence for a local renin-angiotensin system in primary cultured human preadipocytes.  Int J Obes Relat Metab Disord. 1999;  23 336-341
• 3 Karlsson C, Lindell K, Ottosson M, Sjöström L, Carlsson B, Carlsson L MS. Human adipose tissue expresses angiotensinogen and enzymes required for its conversion to angiotensin II.  J Clin Endocrinol Metab. 1998;  83 3925-3929
• 4 Engeli S, Gorzelniak K, Kreutz R, Runkel N, Distler A, Sharma A M. Co-expression of renin-angiotensin system genes in human adipose tissue.  J Hypertens. 1999;  17 555-560
• 5 Engeli S, Negrel R, Sharma A M. Physiology and pathophysiology of the adipose tissue renin-angiotensin system.  Hypertension. 2000;  35 1270-1277
• 6 Engeli S, Sharma A M. Role of adipose tissue for cardiovascular-renal regulation in health and disease.  Horm Metab Res. 2000;  32 485-499
• 7 Cassis L A, Marshall D E, Fettinger M J, Rosenbluth B, Lodder R A. Mechanisms contibuting to angiotensin II regulation of body weight.  Am J Physiol. 1998;  274 E867-E876
• 8 Brink M, Wellen J, Delafontaine P. Angiotensin II causes weight loss and decreases circulating insulin-like growth factor I in rats through a pressor-independent mechanism.  J Clin Invest. 1996;  97 2509-2516
• 9 Crandall D L, Herzlinger H E, Saunders B D, Kral J G. Developmental aspects of the adipose tissue renin-angiotensin system: Therapeutic implications.  Drug Dev Res. 1994;  32 117-125
• 10 Massiera F, Murakami K, Fukamizu A, Negrel R, Ailhaud G, Teboul M. Angiotensinogen deficient mice exhibit alterations in adipose tissue development.  Int J Obes Relat Metab Disord. 1999;  23 (Suppl. 5) 30
• 11 Massiera F, Murakami K, Fukamizu A, Negrel R, Ailhaud G, Teboul M. Effects of high fat diet on adiposity in angiotensinogen deficient and wild type mice.  Eating Weight Disord. 1999;  4 41
• 12 Crandall D L, Armellino D C, Busler D E, McHendry-Rinde B, Kral J G. Angiotensin II receptors in human preadipocytes: role in cell cycle regulation.  Endocrinology. 1999;  140 154-158
• 13 Crandall D L, Armellino D A, Kral J G. Human adipocyte Ang II receptors in primary culture: role in proliferation and differentiation.  Obesity Res. 1997;  5 (Suppl.) 50
• 14 Jones B H, Standridge M K, Moustaid N. Angiotensin II increases lipogenesis in 3T3-L1 and human adipose cells.  Endocrinology. 1997;  138 1512-1519
• 15 Schling P, Löffler G. Angiotensin II receptors during differentiation of human preadipocytes.  Int J Obes Relat Metab Disord. 1998;  22 (Suppl. 3) S99
• 16 Mallow H, Trindl A, Löffler G. Production of angiotensin II receptors type one (AT1) and two (AT2) during the differentiation of 3T3-L1 preadipocytes.  Horm Metab Res. 2000;  32 500-503
• 17 Pairault J, Green H. A study of the adipose conversion of suspended 3T3 cells by using glycerophosphate dehydrogenase as differentiation marker.  Proc Natl Acad Sci USA. 1979;  76 5138-5142
• 18 Wise L S, Green H. Participation of one isozyme of cytosolic glycerophosphate dehydrogenase in the adipose conversion of 3T3 cells.  J Biol Chem. 1979;  254 273-275
• 19 Bradford M M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilising the principle of protein-dye binding.  Anal Biochem. 1976;  72 248-254
• 20 Cassis L A, Dwoskin L P. Presynaptic modulation of neurotransmitter release by endogeneous angiotensin II in brown adipose tissue.  J Neural Transm. 1991;  34 (Suppl.) 129-137
• 21 Ailhaud G. Cross talk between adipocytes and their precursors: relationships with adipose tissue development and blood pressure.  Ann NY Acad Sci. 1999;  892 127-133
• 22 Hwang C S, Loftus T M, Mandrup S, Lane M D. Adipocyte differentiation and leptin expression.  Annu Rev Cell Dev Biol. 1997;  13 231-259
• 23 Gregoire F M, Smas C M, Sul H S. Understanding adipocyte differentiation.  Physiol Rev. 1998;  78 783-809
• 24 Hennington B S, Zhang H, Miller M T, Granger J P, Reckelhoff J F. Angiotensin II stimulated synthesis of endothelial nitric oxide synthase.  Hypertension. 1998;  31 283-288
• 25 Simon G, Abraham G, Cserep G. Pressor and subpressor angiotensin II administration. Two experimental models of hypertension.  Am J Hypertens. 1995;  8 645-650
• 26 Huckle W R, Earp H S. Regulation of cell proliferation and growth by angiotensin II.  Prog Growth Factor Res. 1994;  5 177-194
• 27 Janke J, Gorzelniak K, Engeli S, Sharma A M. Einfluss des Renin-Angiotensin-Systems auf die In-vitro-Differenzierung primärer menschlicher Präadipozyten.  Aktuel Ernähr Med (Abstract). 2000;  25 245
• 28 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
• 29 Saye J A, Lynch K R, Peach M J. Changes in angiotensinogen messenger RNA in differentiating 3T3-F442A adipocytes.  Hypertension. 1990;  15 867-871
• 30 Safonova I, Aubert J, Negrel R, Ailhaud G. Regulation by fatty acids of angiotensinogen gene expression in preadipose cells.  Biochem J. 1997;  322 235-239
• 31 McGehee RE J r., Ron D, Brasier A R, Habener J F. Differentiation specific element: a cis-acting developmental switch required for the sustained transcriptional expression of the angiotensinogen gene during hormonal-induced differentiation of 3T3-L1 fibroblasts to adipocytes.  Mol Endocrinol. 1993;  7 551-560
• 32 Aubert J, Darimont C, Safonova I, Ailhaud G, Negrel R. Regulation by glucocorticoids of angiotensinogen gene expression and secretion in adipose cells.  Biochem J. 1997;  328 701-706
• 33 Harp J B, DiGirolamo M. Components of the renin-angiotensin system in adipose tissue: Changes with maturation and adipose mass enlargement.  J Gerontol A Biol Sci Med Sci. 1995;  50A B270-B276
• 34 Aubert J, Darimont C, Safonova I, Ailhaud G, Negrel R. Regulation by glucocorticoids of angiotensinogen gene expression and secretion in adipose cells.  Biochem J. 1997;  328 701-706
• 35 Inoue H, Takahashi S, Miyake Y. Modulation of active renin secretion by renin-binding protein (RnBP) in mouse pituitary AtT-20 cells transfected with human renin and RnBP cDNAs.  J Biochem. 1992;  111 407-412
• 36 Cary D A, Mendelsohn F AO. Effect of forscolin, isoproterenol and IBMX on angiotensin converting enzyme and cyclic AMP production by cultured bovine endothelial cells.  Mol Cell Endocrinol. 1987;  53 103-109
• 37 Schunkert H, Ingelfinger J R, Hirsch A T, Pinto Y, Remme W J, Jacob H, Dzau V J. Feedback regulation of angiotensin converting enzyme activity and mRNA levels by angiotensin II.  Circ Res. 1993;  72 312-318