|
 |
|
|||||||
|
|||||||||
DOI: 10.2337/diabetes.55.03.06.db05-0917
© 2006 by the American Diabetes Association
Obesity Study |
Metformin Restores Leptin Sensitivity in High-Fat–Fed Obese Rats With Leptin Resistance
1 Department of Physiology, College of Medicine, Yeungnam University, Daegu, Republic of Korea
2 Department of Pediatrics, College of Medicine, Yeungnam University, Daegu, Republic of Korea
3 Aging-Associated Vascular Disease Research Center, College of Medicine, Yeungnam University, Daegu, Republic of Korea
4 Department of Internal Medicine, College of Medicine, Yeungnam University, Daegu, Republic of Korea
5 Department of Urology, College of Medicine, Yeungnam University, Daegu, Republic of Korea
Address correspondence and reprint requests to Yong-Woon Kim, MD, PhD, Department of Physiology, College of Medicine, Yeungnam University, #317-1, Daemyungdong, Namgu, Daegu 705-717, Republic of Korea. E-mail: ywkim{at}med.yu.ac.kr
Abbreviations:
AMPK, AMP-activated protein kinase; CRF, corticotrophin releasing factor; CSF, cerebrospinal fluid; pACC, phosphorylated acetyl-CoA carboxylase; pAMPK, phosphorylated AMPK; pSTAT3, phosphorylated signal transducer and activator of transcription 3; STAT, signal transducer and activator of transcription
To evaluate whether metformin enhances leptin sensitivity, we measured leptin sensitivity after 4 weeks of metformin treatment (300 mg/kg daily) in both standard chow and high-fat–fed obese rats. Anorexic and fat-losing responses after intracerebroventricular leptin infusion for 7 days (15 µg daily per rat) in standard chow rats were enhanced by metformin treatment, and these responses to leptin were attenuated in high-fat–fed obese rats compared with age-matched standard chow rats. However, these responses to leptin were corrected by metformin treatment in high-fat–fed obese rats. Moreover, serum concentrations of leptin and insulin were decreased dramatically by leptin in metformin-treated standard chow and high-fat–fed obese rats. The hypothalamic phosphorylated AMP-activated protein kinase level was decreased by lower leptin dose in metformin-treated rats than in untreated rats. In an acute study, metformin treatment also increased the anorexic effect of leptin (5 µg), and this was accompanied by an increased level of phosphorylated signal transducer and activator of transcription 3 in the hypothalamus. These results suggest that metformin enhances leptin sensitivity and corrects leptin resistance in high-fat–fed obese rats and that a combination therapy including metformin and leptin would be helpful in the treatment of obesity.
CiteULike 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  E. R. Ropelle, J. R. Pauli, K. G. Zecchin, M. Ueno, C. T. de Souza, J. Morari, M. C. Faria, L. A. Velloso, M. J. A. Saad, and J. B. C. Carvalheira A Central Role for Neuronal Adenosine 5'-Monophosphate-Activated Protein Kinase in Cancer-Induced Anorexia Endocrinology, November 1, 2007; 148(11): 5220 - 5229. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. B. Dokken and T.-S. Tsao The Physiology of Body Weight Regulation: Are We Too Efficient for Our Own Good? Diabetes Spectr, July 1, 2007; 20(3): 166 - 170. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-W. Kim, S.-Y. Park, J.-Y. Kim, J.-Y. Huh, W.-S. Jeon, C.-J. Yoon, S.-S. Yun, and K.-H. Moon Metformin Restores the Penile Expression of Nitric Oxide Synthase in High-Fat-Fed Obese Rats J Androl, July 1, 2007; 28(4): 555 - 560. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Chau-Van, M. Gamba, R. Salvi, R. C. Gaillard, and F. P. Pralong Metformin Inhibits Adenosine 5'-Monophosphate-Activated Kinase Activation and Prevents Increases in Neuropeptide Y Expression in Cultured Hypothalamic Neurons Endocrinology, February 1, 2007; 148(2): 507 - 511. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Diabetes | Diabetes Care | Clinical Diabetes | Diabetes Spectrum |