Diabetes, Vol 44, Issue 12 1467-1470, Copyright © 1995 by American Diabetes Association

ARTICLES

The ob gene and insulin. A relationship leading to clues to the understanding of obesity

I Cusin, A Sainsbury, P Doyle, F Rohner-Jeanrenaud and B Jeanrenaud
Laboratories de Recherches Metaboliques, Faculty of Medicine, Geneva University, Switzerland.

Obesity and non-insulin-dependent diabetes are estimated to affect millions of people in the world. This pathology is multifactorial, comprising complex interactions of genetic and environmental factors and lacking a specific therapy. Great interest arose from the recent discovery of the ob gene expressed only in adipose tissue and coding for a protein that appears to regulate adiposity, potentially by acting as a satiety factor. We report here that in normal rats, ob mRNA is respectively up- or downregulated by a rise in insulinemia (induced by 2-day insulin infusion while maintaining euglycemia) or a decrease in insulinemia (induced by a 3-day fast). Our results also show that in genetically obese fa/fa rats studied longitudinally, white adipose tissue ob mRNA levels increase in parallel with early occurring and steadily increasing hyperinsulinemia. This results in adult obese animals having markedly higher ob mRNA levels than age-matched normoinsulinemic lean rats. Furthermore, in adult obese rats, ob mRNA escapes down-regulation as normalization of hyperinsulinemia due to fasting fails to reduce the high ob mRNA levels.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				B. Amasyali, K. Aytemir, S. Kose, A. Kilic, G. Abali, A. Iyisoy, H. Kursaklioglu, M. Turan, N. Bingol, E. Isik, et al. Admission Plasma Leptin Level Strongly Correlates With the Success of Thrombolytic Therapy in Patients With Acute Myocardial Infarction Angiology, January 1, 2007; 57(6): 671 - 680. [Abstract] [PDF]

				C. Garofalo, M. Koda, S. Cascio, M. Sulkowska, L. Kanczuga-Koda, J. Golaszewska, A. Russo, S. Sulkowski, and E. Surmacz Increased Expression of Leptin and the Leptin Receptor as a Marker of Breast Cancer Progression: Possible Role of Obesity-Related Stimuli Clin. Cancer Res., March 1, 2006; 12(5): 1447 - 1453. [Abstract] [Full Text] [PDF]

				J. A. Cartmill, D. L. Thompson Jr., W. A. Storer, J. C. Crowley, N. K. Huff, and C. A. Waller Effect of dexamethasone, feeding time, and insulin infusion on leptin concentrations in stallions J Anim Sci, August 1, 2005; 83(8): 1875 - 1881. [Abstract] [Full Text] [PDF]

				J. Boucher, B. Masri, D. Daviaud, S. Gesta, C. Guigne, A. Mazzucotelli, I. Castan-Laurell, I. Tack, B. Knibiehler, C. Carpene, et al. Apelin, a Newly Identified Adipokine Up-Regulated by Insulin and Obesity Endocrinology, April 1, 2005; 146(4): 1764 - 1771. [Abstract] [Full Text] [PDF]

				J. M. Zigman and J. K. Elmquist Minireview: From Anorexia to Obesity--The Yin and Yang of Body Weight Control Endocrinology, September 1, 2003; 144(9): 3749 - 3756. [Abstract] [Full Text] [PDF]

				J. A. Cartmill, D. L. Thompson Jr., W. A. Storer, L. R. Gentry, and N. K. Huff Endocrine responses in mares and geldings with high body condition scores grouped by high vs. low resting leptin concentrations J Anim Sci, September 1, 2003; 81(9): 2311 - 2321. [Abstract] [Full Text] [PDF]

				A. E. Kitabchi and G. E. Umpierrez Changes in Serum Leptin in Lean and Obese Subjects with Acute Hyperglycemic Crises J. Clin. Endocrinol. Metab., June 1, 2003; 88(6): 2593 - 2596. [Abstract] [Full Text] [PDF]

				C. K. Roberts, J. J. Berger, and R. J. Barnard Long-term effects of diet on leptin, energy intake, and activity in a model of diet-induced obesity J Appl Physiol, September 1, 2002; 93(3): 887 - 893. [Abstract] [Full Text] [PDF]

				E. Peyron-Caso, M. Taverna, M. Guerre-Millo, A. Veronese, N. Pacher, G. Slama, and S. W. Rizkalla Dietary (n-3) Polyunsaturated Fatty Acids Up-Regulate Plasma Leptin in Insulin-Resistant Rats J. Nutr., August 1, 2002; 132(8): 2235 - 2240. [Abstract] [Full Text] [PDF]

				E. Charmandari, M. Weise, S. R. Bornstein, G. Eisenhofer, M. F. Keil, G. P. Chrousos, and D. P. Merke Children with Classic Congenital Adrenal Hyperplasia Have Elevated Serum Leptin Concentrations and Insulin Resistance: Potential Clinical Implications J. Clin. Endocrinol. Metab., May 1, 2002; 87(5): 2114 - 2120. [Abstract] [Full Text] [PDF]

				T. S. Herrmann, M. L. Bean, T. M. Black, P. Wang, and R. A. Coleman High Glycemic Index Carbohydrate Diet Alters the Diurnal Rhythm of Leptin But Not Insulin Concentrations Experimental Biology and Medicine, December 1, 2001; 226(11): 1037 - 1044. [Abstract] [Full Text] [PDF]

				P C Ng, C W K Lam, C H Lee, G W K Wong, T F Fok, E Wong, K C Ma, and I H S Chan Leptin and metabolic hormones in infants of diabetic mothers Arch. Dis. Child. Fetal Neonatal Ed., November 1, 2000; 83(3): 193F - 197. [Abstract] [Full Text]

				C Berry and A.L Clark Catabolism in chronic heart failure Eur. Heart J., April 1, 2000; 21(7): 521 - 532. [PDF]

				A. Suga, T. Hirano, H. Kageyama, T. Osaka, Y. Namba, M. Tsuji, M. Miura, M. Adachi, and S. Inoue Effects of fructose and glucose on plasma leptin, insulin, and insulin resistance in lean and VMH-lesioned obese rats Am J Physiol Endocrinol Metab, April 1, 2000; 278(4): E677 - E683. [Abstract] [Full Text] [PDF]

				T. J. Kieffer and J. F. Habener The adipoinsular axis: effects of leptin on pancreatic beta -cells Am J Physiol Endocrinol Metab, January 1, 2000; 278(1): E1 - E14. [Abstract] [Full Text] [PDF]

				L. De Marinis, A. Mancini, D. Valle, A. Bianchi, D. Milardi, A. Proto, A. Lanzone, and R. Tacchino Plasma Leptin Levels after Biliopancreatic Diversion: Dissociation with Body Mass Index J. Clin. Endocrinol. Metab., July 1, 1999; 84(7): 2386 - 2389. [Abstract] [Full Text]

				K. E. Zakrzewska, A. Sainsbury, I. Cusin, J. Rouru, B. Jeanrenaud, and F. Rohner-Jeanrenaud Selective Dependence of Intracerebroventricular Neuropeptide Y-Elicited Effects on Central Glucocorticoids Endocrinology, July 1, 1999; 140(7): 3183 - 3187. [Abstract] [Full Text]

				R. Alemzadeh and S. Holshouser Effect of Diazoxide on Brain Capillary Insulin Receptor Binding and Food Intake in Hyperphagic Obese Zucker Rats Endocrinology, July 1, 1999; 140(7): 3197 - 3202. [Abstract] [Full Text]

				M. W Schwartz, D. G Baskin, K. J Kaiyala, and S. C Woods Model for the regulation of energy balance and adiposity by the central nervous system Am. J. Clinical Nutrition, April 1, 1999; 69(4): 584 - 596. [Abstract] [Full Text] [PDF]

				M. Shaarawy and S. Y. El-Mallah Leptin and Gestational Weight Gain: Relation of Maternal and Cord Blood Leptin to Birth Weight Reproductive Sciences, March 1, 1999; 6(2): 70 - 73. [Abstract] [PDF]

				J. M. Bryson, J. L. Phuyal, D. R. Proctor, S. C. Blair, I. D. Caterson, and G. J. Cooney Plasma insulin rise precedes rise in ob mRNA expression and plasma leptin in gold thioglucose-obese mice Am J Physiol Endocrinol Metab, February 1, 1999; 276(2): E358 - E364. [Abstract] [Full Text] [PDF]

				F-X. Pi-Sunyer and B. Laferrère Metabolic Abnormalities and the Role of Leptin in Human Obesity J. Clin. Endocrinol. Metab., January 1, 1999; 84(1): 3 - 7. [Full Text]

				F. Leyva, I. F. Godsland, M. Ghatei, A. J. Proudler, S. Aldis, C. Walton, S. Bloom, and J. C. Stevenson Hyperleptinemia as a Component of a Metabolic Syndrome of Cardiovascular Risk Arterioscler. Thromb. Vasc. Biol., June 1, 1998; 18(6): 928 - 933. [Abstract] [Full Text] [PDF]

				P. J. Havel, J. Y. Uriu-Hare, T. Liu, K. L. Stanhope, J. S. Stern, C. L. Keen, and B. Ahren Marked and rapid decreases of circulating leptin in streptozotocin diabetic rats: reversal by insulin Am J Physiol Regulatory Integrative Comp Physiol, May 1, 1998; 274(5): R1482 - R1491. [Abstract] [Full Text] [PDF]

				A. Widjaja, T. H. Schürmeyer, A. Von Zur Mühlen, and G. Brabant Determinants of Serum Leptin Levels in Cushing's Syndrome J. Clin. Endocrinol. Metab., February 1, 1998; 83(2): 600 - 603. [Abstract] [Full Text]

				W. M. Mueller, F. M. Gregoire, K. L. Stanhope, C. V. Mobbs, T. M. Mizuno, C. H. Warden, J. S. Stern, and P. J. Havel Evidence That Glucose Metabolism Regulates Leptin Secretion from Cultured Rat Adipocytes Endocrinology, February 1, 1998; 139(2): 551 - 558. [Abstract] [Full Text] [PDF]

				W. J. Pasman, M. S. Westerterp-Plantenga, and W. H. M. Saris The effect of exercise training on leptin levels in obese males Am J Physiol Endocrinol Metab, February 1, 1998; 274(2): E280 - E286. [Abstract] [Full Text] [PDF]

				W. T. Donahoo, D. R. Jensen, T. J. Yost, and R. H. Eckel Isoproterenol and Somatostatin Decrease Plasma Leptin in Humans: A Novel Mechanism Regulating Leptin Secretion J. Clin. Endocrinol. Metab., December 1, 1997; 82(12): 4139 - 4143. [Abstract] [Full Text] [PDF]

				C. S. Mantzoros, S. Moschos, I. Avramopoulos, V. Kaklamani, A. Liolios, D. E. Doulgerakis, I. Griveas, N. Katsilambros, and J. S. Flier Leptin Concentrations in Relation to Body Mass Index and the Tumor Necrosis Factor-{alpha} System in Humans J. Clin. Endocrinol. Metab., October 1, 1997; 82(10): 3408 - 3413. [Abstract] [Full Text] [PDF]

				W. F. Blum, P. Englaro, S. Hanitsch, A. Juul, N. T. Hertel, J. Muller, N. E. Skakkebak, M. L. Heiman, M. Birkett, A. M. Attanasio, et al. Plasma Leptin Levels in Healthy Children and Adolescents: Dependence on Body Mass Index, Body Fat Mass, Gender, Pubertal Stage, and Testosterone J. Clin. Endocrinol. Metab., September 1, 1997; 82(9): 2904 - 2910. [Abstract] [Full Text] [PDF]

				W. G. Haynes, W. I. Sivitz, D. A. Morgan, S. A. Walsh, and A. L. Mark Sympathetic and Cardiorenal Actions of Leptin Hypertension, September 1, 1997; 30(3): 619 - 623. [Abstract] [Full Text]

				L. Perusse, G. Collier, J. Gagnon, A. S. Leon, D. C. Rao, J. S. Skinner, J. H. Wilmore, A. Nadeau, P. Z. Zimmet, and C. Bouchard Acute and chronic effects of exercise on leptin levels in humans J Appl Physiol, July 1, 1997; 83(1): 5 - 10. [Abstract] [Full Text] [PDF]

				S. B. Racette, S. W. Coppack, M. Landt, and S. Klein Leptin Production during Moderate-Intensity Aerobic Exercise J. Clin. Endocrinol. Metab., July 1, 1997; 82(7): 2275 - 2277. [Abstract] [Full Text] [PDF]

				C. S. Mantzoros, A. Dunaif, and J. S. Flier Leptin Concentrations in the Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., June 1, 1997; 82(6): 1687 - 1691. [Abstract] [Full Text] [PDF]

				G. A. Laughlin, A. J. Morales, and S. S. C. Yen Serum Leptin Levels in Women with Polycystic Ovary Syndrome: The Role of Insulin Resistance/ Hyperinsulinemia J. Clin. Endocrinol. Metab., June 1, 1997; 82(6): 1692 - 1696. [Abstract] [Full Text] [PDF]

				C. S. Mantzoros, J. S. Flier, and A. D. Rogol A Longitudinal Assessment of Hormonal and Physical Alterations during Normal Puberty in Boys. V. Rising Leptin Levels May Signal the Onset of Puberty J. Clin. Endocrinol. Metab., April 1, 1997; 82(4): 1066 - 1070. [Abstract] [Full Text] [PDF]

				A. Kennedy, T. W. Gettys, P. Watson, P. Wallace, E. Ganaway, Q. Pan, and W. T. Garvey The Metabolic Significance of Leptin in Humans: Gender-Based Differences in Relationship to Adiposity, Insulin Sensitivity, and Energy Expenditure J. Clin. Endocrinol. Metab., April 1, 1997; 82(4): 1293 - 1300. [Abstract] [Full Text] [PDF]

				N. Satoh, Y. Ogawa, G. Katsuura, T. Tsuji, H. Masuzaki, J. Hiraoka, T. Okazaki, M. Tamaki, M. Hayase, Y. Yoshimasa, et al. Pathophysiological Significance of the Obese Gene Product, Leptin, in Ventromedial Hypothalamus (VMH)-Lesioned Rats: Evidence for Loss of Its Satiety Effect in VMH-Lesioned Rats Endocrinology, March 1, 1997; 138(3): 947 - 954. [Abstract] [Full Text] [PDF]

				D. S. Weigle, P. B. Duell, W. E. Connor, R. A. Steiner, M. R. Soules, and J. L. Kuijper Effect of Fasting, Refeeding, and Dietary Fat Restriction on Plasma Leptin Levels J. Clin. Endocrinol. Metab., February 1, 1997; 82(2): 561 - 565. [Abstract] [Full Text] [PDF]

				D. S. Weigle, S. L. Ganter, J. L. Kuijper, D. L. Leonetti, E. J. Boyko, and W. Y. Fujimoto Effect of Regional Fat Distribution and Prader-Willi Syndrome on Plasma Leptin Levels J. Clin. Endocrinol. Metab., February 1, 1997; 82(2): 566 - 570. [Abstract] [Full Text] [PDF]

				N. F. Butte, J. M. Hopkinson, and M. A. Nicolson Leptin in Human Reproduction: Serum Leptin Levels in Pregnant and Lactating Women J. Clin. Endocrinol. Metab., February 1, 1997; 82(2): 585 - 589. [Abstract] [Full Text] [PDF]

				A. Widjaja, I. M. Stratton, R. Horn, R. R. Holman, R. Turner, and G. Brabant UKPDS 20: Plasma Leptin, Obesity, and Plasma Insulin in Type 2 Diabetic Subjects J. Clin. Endocrinol. Metab., February 1, 1997; 82(2): 654 - 657. [Abstract] [Full Text] [PDF]

				P. Zimmet, A. Hodge, M. Nicolson, M. Staten, M. de Courten, J. Moore, A. Morawiecki, J. Lubina, G. Collier, G. Alberti, et al. Serum leptin concentration, obesity, and insulin resistance in Western Samoans: cross sectional study BMJ, October 19, 1996; 313(7063): 965 - 969. [Abstract] [Full Text]

				K. Hotta, T. A. Gustafson, H. K. Ortmeyer, N. L. Bodkin, M. A. Nicolson, and B. C. Hansen Regulation of obese (ob) mRNA and Plasma Leptin Levels in Rhesus Monkeys. EFFECTS OF INSULIN, BODY WEIGHT, AND NON-INSULIN-DEPENDENT DIABETES MELLITUS J. Biol. Chem., October 11, 1996; 271(41): 25327 - 25331. [Abstract] [Full Text] [PDF]

				F. Rohner-Jeanrenaud and B. Jeanrenaud Obesity, Leptin, and the Brain N. Engl. J. Med., February 1, 1996; 334(5): 324 - 325. [Full Text]