HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Free Full Text (PDF) Free Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by STANDRIDGE, M. Articles by MOUSTAID-MOUSSA, N. Search for Related Content PubMed PubMed Citation Articles by STANDRIDGE, M. Articles by MOUSTAID-MOUSSA, N.

Diazoxide down-regulates leptin and lipid metabolizing enzymes in adipose tissue of Zucker rats

MELISSA STANDRIDGE^*, RAMIN ALEMZADEH, MICHAEL ZEMEL^*, JOHN KOONTZ and NAIMA MOUSTAID-MOUSSA^*1

Departments of
^* Nutrition and
Biochemistry, Cellular and Molecular Biology, University of Tennessee, Knoxville Tennessee 37996, USA; and
Department of Pediatrics, University of Tennessee, Medical Center, Knoxville, Tennessee 37920, USA

¹Correspondence: University of Tennessee, 1215 Cumberland Ave., Department of Nutrition JHB 229, Knoxville, Tennessee 37996-1900, USA. E-mail:moustaid{at}utk.edu

We have previously reported that attenuation of hyperinsulinemia by diazoxide (DZ), an inhibitor of glucose-mediated insulin secretion, increased insulin sensitivity and reduced body weight in obese Zucker rats. These findings prompted us to investigate the effects of DZ on key insulin-sensitive enzymes regulating adipose tissue metabolism, fatty acid synthase (FAS), and lipoprotein lipase (LPL), as well as on circulating levels of leptin. We also determined the direct effects of diazoxide on FAS in 3T3-L1 adipocytes. Seven-week-old female obese and lean Zucker rats were treated with DZ (150 mg/kg/d) or vehicle (C, control) for a period of 6 wk. Changes in plasma parameters by DZ include significant decreases in triglycerides, free fatty acids, glucose, and insulin, consistent with our previous reports. DZ obese rats exhibited lower plasma leptin levels (P<0.03) compared to their C animals. DZ significantly reduced adipose tissue FAS activity in both lean (P<0.0001) and obese (P<0.01) animals. LPL mRNA content was also decreased significantly in DZ-treated obese animals (P<0.009) as compared to their respective controls without a significant effect on lean animals. The possibility that DZ exerted a direct effect on adipocytes was further tested in cultured 3T3-L1 adipocytes. Although diazoxide (5 µM) alone did not change FAS activity in cultured 3T3-L1 adipocytes, it significantly attenuated insulin’s effect on FAS activity (P<0.001). We demonstrate that DZ regulates key insulin-sensitive enzymes involved in regulation of adipose tissue metabolism. These findings suggest that modification of insulin-sensitive pathways can be therapeutically beneficial in obesity management.—Standridge, M., Alemzadeh, R., Zemel, M., Koontz, J., Moustaid-Moussa, N. Diazoxide down-regulates leptin and lipid metabolizing enzymes in adipose tissue of Zucker rats

Key Words: lipoprotein lipase • fatty acid synthase • insulin • glucose • adipocytes

This article has been cited by other articles:

				P. A. Baldock, S. J. Allison, P. Lundberg, N. J. Lee, K. Slack, E.-J. D. Lin, R. F. Enriquez, M. M. McDonald, L. Zhang, M. J. During, et al. Novel Role of Y1 Receptors in the Coordinated Regulation of Bone and Energy Homeostasis J. Biol. Chem., June 29, 2007; 282(26): 19092 - 19102. [Abstract] [Full Text] [PDF]

				A. Sainsbury, H. T. Bergen, D. Boey, D. Bamming, G. J. Cooney, S. Lin, M. Couzens, N. Stroth, N. J. Lee, D. Lindner, et al. Y2Y4 Receptor Double Knockout Protects Against Obesity Due to a High-Fat Diet or Y1 Receptor Deficiency in Mice Diabetes, January 1, 2006; 55(1): 19 - 26. [Abstract] [Full Text] [PDF]

				M. B. Zemel The Role of Dairy Foods in Weight Management J. Am. Coll. Nutr., December 1, 2005; 24(suppl_6): 537S - 546S. [Abstract] [Full Text] [PDF]

				R. Alemzadeh and K. M. Tushaus Modulation of Adipoinsular Axis in Prediabetic Zucker Diabetic Fatty Rats by Diazoxide Endocrinology, December 1, 2004; 145(12): 5476 - 5484. [Abstract] [Full Text] [PDF]

				J. M. Harkins, N. Moustaid-Moussa, Y.-J. Chung, K. M. Penner, J. J. Pestka, C. M. North, and K. J. Claycombe Expression of Interleukin-6 Is Greater in Preadipocytes than in Adipocytes of 3T3-L1 Cells and C57BL/6J and ob/ob Mice J. Nutr., October 1, 2004; 134(10): 2673 - 2677. [Abstract] [Full Text] [PDF]

				M. B. Zemel Mechanisms of Dairy Modulation of Adiposity J. Nutr., January 1, 2003; 133(1): 252S - 256. [Abstract] [Full Text] [PDF]

				K. Baran, E. Preston, D. Wilks, G. J. Cooney, E. W. Kraegen, and A. Sainsbury Chronic Central Melanocortin-4 Receptor Antagonism and Central Neuropeptide-Y Infusion in Rats Produce Increased Adiposity by Divergent Pathways Diabetes, January 1, 2002; 51(1): 152 - 158. [Abstract] [Full Text] [PDF]

				S. Bassilian, S. Ahmed, S. K. Lim, L. G. Boros, C. S. Mao, and W.-N. P. Lee Loss of regulation of lipogenesis in the Zucker diabetic rat. II. Changes in stearate and oleate synthesis Am J Physiol Endocrinol Metab, March 1, 2002; 282(3): E507 - E513. [Abstract] [Full Text] [PDF]