Abstract
The effects of vanadate administration on the plasma lipids and hepatic lipogenic enzymes were investigated in Zucker (fa/fa) rat, a model for obesity and non insulin-dependent diabetes. These animals were administered sodium orthovanadate through drinking water for a period of four months. The plasma levels of insulin, triacylglycerols and total cholesterol were significantly (p < 0.001) elevated in untreated obese control rats as compared to the lean animals. In the livers of obese rats, the number of insulin receptors decreased by 60% and the activities of lipogenic enzymes acetyl-CoA carboxylase and ATP-citrate lyase increased by 4.7- and 5.6-folds, respectively. The messenger RNA for ATP-citrate lyase as measured by Northern blot analysis showed a parallel increase in obese control rats. Treatment of these rats with vanadate caused 56–77% decreases in the plasma levels of insulin, triacylglycerols and total cholesterol. The insulin receptor numbers in vanadate-treated obese rats increased (119%) compared to levels in untreated obese animals. The elevated activities of acetyl-CoA carboxylase and ATP-citrate lyase observed in livers of obese rats were significantly reduced by vanadate. The messenger RNA for ATP-citrate lyase also decreased in vanadate-treated obese rats back to the lean control levels. This study demonstrates that vanadate exerts potent actions on lipid metabolism in diabetic animals in addition to the recognized effects on glucose homeostasis.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Bray GA: The Zucker-fatty rat: a review. Federation Proc 36: 148–153, 1977
Dugail I, Quignard-Boulange A, Le Liepvre X, Ardouin B, Lavau M: Gene expression of lipid storage related enzymes in adipose tissue of the genetically obese Zucker rat. Biochem J 281: 607–611, 1992
Martin RJ: In vivo lipogenesis and enzyme levels in adipose and liver tissues from pair-fed genetically obese and lean rats. Life Sciences 14: 1447–1453, 1974
Santen RJ, Willis PW, Fajans SS: Atherosclerosis in diabetes mellitus. Correlations with serum lipid levels, adiposity, and serum insulin level. Arch Intern Med 130: 833–843, 1972
Shechter Y: Insulin-mimetic effects of vanadate. Possible implications for future treatment of diabetes. Diabetes 39: 1–5, 1990
Khandelwal RL, Pugazhenthi S: In vivo effects of vanadate on hepatic glycogen metabolizing and lipogenic enzymes in insulin-dependent and insulin-resistant diabetic animals. Mol Cell Biochem 153: 87–94
Pugazhenthi S, Khandelwal RL: Insulin-like effects of vanadate on hepatic glycogen metabolism in nondiabetic and streptozocin-induced diabetic rats. Diabetes 39: 821–827, 1990
Pugazhenthi S, Angel JF, Khandelwal RL: Long-term effects of vanadate treatment on glycogen metabolizing and lipogenic enzymes of liver in genetically diabetic (db/db) mice. Metabolism 40: 941–946, 1991
Brichard SM, Pottier AM, Henquin JC: Long term improvement of glucose homeostasis by vanadate in obese hyperinsulinemic fa/fa rats. Endocrinology 125: 2510–2516, 1989
Brichard SM, Assimacopoulos-Jeannet F, Jeanrenaud B: Vanadate treatment markedly increases glucose utilization in muscle of insulin-resistant fa/fa rats without modifying glucose transporter expression. Endocrinology 131: 311–317, 1992
Fantus IG, Ahmad F, Deragon G: Vanadate augments insulin binding and prolongs insulin action in rat adipocytes. Endocrinology 127: 2716–2725, 1990
Pugazhenthi S, Angel JF, Khandelwal RL: Effects of vanadate administration on the high sucrose diet-induced aberrations in normal rats. Mol Cell Biochem 122, 69–75, 1993
Winz R, Hess D, Aebersold R, Brownsey RW: Unique structural features and differential phosphorylation of the 280-kDa component (Isozyme) of rat liver acetyl CoA carboxylase. J Biol Chem 269: 14438–14445, 1994
Pugazhenthi S, Khandelwal RL: Does the insulin-mimetic action of vanadate involve insulin receptor kinase? Mol cell Biochem 127/128, 211–218, 1993
Chomczyhnski P, Sacchi N: Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction, Anal Biochem 162, 156–159, 1987
Elshourbagy NA, Near JC, Kmetz PJ, Sathe GM, Southan C, Strickler JE, Gross M, Young JF, Wells TNC, Groot PHE. Rat ATP Citrate-lyase. J Biol Chem 265: 1430–1435, 1990
Guerre-Millo M, Lavau M, Home JS, Wardzala LJ: Proposed mechanism for increased insulin-mediated glucose transport in adipose cells from young, obese Zucker rats. J Biol Chem 260: 2197–2201, 1985
Debant A, Guerre-Millo M, Marchand-Brustel YL, Freychet P, Lavau M, Van Obberghen E: Insulin receptor kinase is hyperresponsive in adipocytes of young obese Zucker rats. Am J Physiol 252: E273–E278, 1987
Godbole V, York DA: Lipogenesis in situ in the genetically obese Zucker fatty rat (fa/fa): Role of hyperphagia and hyperinsulinemia. Diabetologia 14: 191–197, 1978
McCune SA, Durant PJ, Jenkins PA, Harris RA: Comparative studies on fatty acid synthesis, glycogen metabolism, and gluconeogenesis by hepatocytes isolated from lean and obese Zucker rats. Metabolism 30: 1170–1178, 1981
Henquin JC, Carton F, Ongemba LN, Becker DJ: Improvement of mild hypoinsulinemic diabetes in the rat by low non-toxic doses of vanadate. J Endocrinol 142: 555–561, 1994
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1995 Kluwer Academic Publishers
About this chapter
Cite this chapter
Pugazhenthi, S., Hussain, A., Yu, B., Brownsey, R.W., Angel, J.F., Khandelwal, R.L. (1995). Vanadate induces normolipidemia and a reduction in the levels of hepatic lipogenic enzymes in obese Zucker rat. In: Srivastava, A.K., Chiasson, JL. (eds) Vanadium Compounds: Biochemical and Therapeutic Applications. Developments in Molecular and Cellular Biochemistry, vol 16. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-1251-2_28
Download citation
DOI: https://doi.org/10.1007/978-1-4613-1251-2_28
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4612-8533-5
Online ISBN: 978-1-4613-1251-2
eBook Packages: Springer Book Archive