Glucose and insulin levels in Wistar rats submitted to high fat diet and treatment with mimetic leptin peptides

Elpidia Poveda, Pilar Trujillo, Francisco Ruiz, Elizabeth Lopez, .

Keywords: blood glucose, insulin, dietary fats, peptides, leptin, rats, Wistar

Abstract

Introduction. Studies on leptin administration have demonstrated a reversion of insulin resistance, and that leptin produces effects in glucose metabolism.
Objective. Changes in the insulin and glucose concentrations in blood plasma was valuated by intraperitoneal administration of mimetic leptin peptides in Wistar rats fed with high fat diet.
Materials and methods. A control group of rats was defined that were fed with high fat diet and a control group with normal diet. Several treatments groups were fed with high fat diet and subjected to the administration of seven different mimetic leptin peptides, each one administered in four different concentrations. During the peptide administration the glucose concentrations were quantified and at the end the insulin concentrations.
Results. The average insulin concentrations in the control groups were similar; however, hyperinsulinemia was observed in the groups to which we administered the peptide denominated 83 at doses of 10 mg/kg and 20 mg/kg of body weight. All the treatment groups except the peptide denominated with the code 80 showed diminished glucose levels even in the cases without hyperglycemia.  The greatest effect was observed with the peptide 116-130 of the mouse leptin and its human homolog, although without statistical differences with the other treatments.
Conclusion. Lectin peptides have no effect on the insulin plasma concentrations; however, an effect is evident in glucose levels.  Additional research will be required to determine if leptin mimetic peptides influence the glucose metabolism or the expression, secretion, signaling mechanism and regulation of insulin.

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  • Elpidia Poveda Grupo de Nutrición, Subdirección de Investigación, Instituto Nacional de Salud, Bogotá, D.C., Colombia
  • Pilar Trujillo Departamento de Nutrición y Bioquímica, Pontificia Universidad Javeriana, Bogotá, D.C., Colombia
  • Francisco Ruiz Bioterio, Instituto Nacional de Salud, Bogotá, D.C., Colombia
  • Elizabeth Lopez Grupo de Sociedad y Salud, Subdirección de Investigación, Instituto Nacional de Salud, Bogotá, D.C., Colombia

References

1. Friedman JM, Halaas  JL. Leptin and the regulation of body weight in mammals. Nature. 1998; 395: 763-70.
2. Zhang Y, Proenca R, Maffei M, Barone  M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature. 1994; 372: 425-32.
3. Madej  T, Boguski MS, Bryant SH. Threading analysis suggest that the obese gene product may be a helical cytokine. FEBS Lett. 1995; 373: 13-8.
4. Zhang  F, Basinski MB, Beals  JM, Briggs SL, Churgay LM, Clawson DK, et al. Crystal structure of the obese protein leptin-E100. Nature. 1997; 387: 206-9.
5. Cammisotto PG, Bukowiecki LJ. Mechanisms of leptin secretion from white adipocytes. Am J Physiol Cell Physiol. 2002; 283: C244-50.
6. Considine RV. Human leptin: an adipocyte hormone with weight-regulatory and endocrine functions. Semin Vasc Med. 2005; 5: 15-24.
7. Rayner DV, Trayhurn  P. Regulation of leptin production: sympathetic nervous system interactions. J Mol Med. 2001; 79: 8-20.
8. Fruhbeck  G, Aguado  M, Martinez JA. In vitro lipolytic effect of leptin on mouse adipocytes: evidence for a possible autocrine/paracrine role of leptin. Biochem Biophys Res Commun. 1997; 240: 590-4.
9. Hakansson  ML, Brown  H, Ghilardi N, Skoda  RC, Meister B. Leptin receptor immunoreactivity in chemically defined target neurons of the hypothalamus. J Neurosci. 1998; 18: 559-72.
10. Spiegelman BM, Flier  JS. Obesity and the regulation of energy balance. Cell. 2001; 104: 531-43.
11. Grill  HJ, Schwartz  MW, Kaplan JM, Foxhall JS, Breininger J, Baskin DG. Evidence that the caudal brainstem is a target for the inhibitory effect of leptin on food intake. Endocrinology. 2002; 143: 239-46.
12. Jacob  RJ, Dziura  J, Medwixk  MB, Leone P, Caprio S, During  M, et al. The effect of leptin is enhanced by microinjection into the ventromedial hypothalamus. Diabetes 1997; 46: 150-2.
13. Mercer JG, Hoggard  N, Williams  LM; Lawrence  CB, Hannah  LT, Trahurn P. Localization of leptin receptor mRNA and the long form splice variant (Ob-Rb) in mouse hypothalamus and adjacent brain region by in situ hybridization. FEBS Lett. 1996; 387: 113-6.
14. Savioz A, Charnay  Y, Huguenin  C, Graviou C, Greggio B, Bouras  C. Expression of leptin receptor mRNA (long form splice variant) in the human cerebellum. Neuroreport. 1997; 8: 3123-6.
15. Schwarts MW, Seeley RJ, Campfield LA, Burn  P, Baskin DG. Identification of targets of leptin action in rat hypothalamus. J Clin Invest. 1996; 98: 1101-6.
16. Grasso  P, Leinung  MC, Ingher  SP, Lee DW. In vivo effects of leptin related synthetic peptides on body weight and food intake in female ob/ob mice. Localization of leptin activity to domains between aminoacid residues 106-140. Endocrinology. 1997; 138: 1413-8.
17. Rozhavskaya-Arena  M, Lee  DW, Leinung  MC, Grasso P. Design of a synthetic leptin agonist: effects on energy balance, glucose homeostasis, and thermoregulation. Endocrinology. 2000; 141: 2501-7.
18. Lin S, Thomas TC, Storlien  LH, Huang XF. Development of high fat diet-induced obesity and leptin resistance in C57Bl/6J mice. Int J Obes Relat Metab Disord. 2000; 24: 639-46.
19. Vasselli JR. Behavioral and biological determinants of leptin resistance. Appetite. 2001; 37: 115-7.
20. Fernandez-Galaz C, Fernandez-Agullo T, Perez  C, Peralta  S, Arribas  C, Andres  A, et al. Long-term food restriction prevents ageing-associated central leptin resistance in wistar rats. Diabetologia. 2002; 45: 997-1003.
21. Kim-Motoyama  H, Yamaguchi  T, Katakura  T, Miura M, Ohashi Y, Yazaki Y, et al. Serum leptin levels are associated with hyperinsulinemia independent of body mass index but not with visceral obesity. Biochem Biophys Res Commun. 1997; 239: 340-4.
22. Dagogo-Jack  S, Fanelli C, Paramore D, Brothers  J, Landt  M. Plasma leptin and insulin relationships in obese and nonobese humans. Diabetes. 1996; 45: 695-8.
23. Sahu A. Leptin signaling in the hypothalamus: emphasis on energy homeostasis and leptin resistance. Front Neuroendocrinol. 2003; 24: 225-53.
24. Steinberg GR, Dyck  DJ. Development of leptin resistance in rat soleus muscle in response to high-fat diets. Am J Physiol Endocrinol Metab. 2000; 279: E1374-82.
25. Wang J, Obici S, Morgan  K, Barzilai N, Feng  Z, Rossetti L. Overfeeding rapidly induces leptin and insulin resistance. Diabetes. 2001; 50: 2786-91.
26. Yaspelkis  B 3rd, Singh  MK, Krisan AD, Collins DE, Kwong  CC, Bernard JR, et al. Chronic leptin treatment enhances insulin-stimulated glucose disposal in skeletal muscle of high-fat fed rodents. Life Sci. 2004; 74: 1801-16.
27. Muller  G, Ertl J, Gerl  M, Preibisch  G. Leptin impairs metabolic actions of insulin in isolated rat adipocytes. J Biol Chem. 1997; 272: 10585-93.
28. Walder  K, Filipps  A, Clark S, Zimmet  P, Collier GR. Leptin inhibits insulin binding in isolated rat adipocytes. J Endocrinol. 1997; 155: R5-7.
29. Zhao  AZ, Bornfeldt KE, Beavo  JA. Leptin inhibits insulin secretion by activation of phosphodiesterase 3B. J Clin Invest. 1998; 102: 869-73.
30. Sweeney G, Keen J, Somwar  R, Konrad  D, Garg  R, Klip A. High leptin levels acutely inhibit insulin-stimualted glucose uptake without affecting glucose transporter 4 traslocation in L6 rat skeletal muscle cells. Endocrinology.  2001; 142: 4806-12.
31. Pérez C, Fernández-Galaz C, Fernández-Agulló T, Arribas  C, Andrés A, Ros M, et al. Leptin impairs insulin signaling in rat adipocytes. Diabetes. 2004; 53: 347-53.
32. Sivitz  WI, Walsh  SA, Morgan  DA, Thomas  MJ, Haynes WG. Effects of leptin on insulin sensitivity in normal rats. Endocrinology. 1997; 138: 3395-401.
33. Lichnovska  R, Gwozdziewiczova S, Chlup R, Hrebicek  J. Serum leptin in the development of insulin resistance and other disorders in the metabolic syndrome. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2005; 149: 119-26.
34. Havel PJ, Kasim-Karakas S, Mueller W, Johnson  PR, Gingerich  RL, Stern JS. Relationship of plasma leptin to plasma insulin and adiposity in normal weight and overweight women: effects of dietary fat content and sustained weight loss. J Clin Endocrinol Metab. 1996; 81: 4406-13.
35. Guven  S, El-Bershawi A, Sonnenberg  GE, Wilson CR, Hoffmann RG, Krakower  GR, et al. Plasma leptin and insulin levels in weight-reduced obese women with normal body mass index: relationships with body composition and insulin. Diabetes. 1999; 48: 347-52.
36. Barr  VA, Malide  D, Zarnowski  MJ, Taylor  SI, Cushman  SW. Insulin stimulates both leptin secretion and production by rat white adipose tissue. Endocrinology. 1997; 138: 4463-72.
37. Doucet  E, ST-Pierre S, Almeras  N, Mauriege P, Despres J, Richard D, et al. Fasting insulin levels influence plasma leptin levels independently from the contribution of adiposity: evidence from both a cross-sectional and an intervention study. J Clin Endocrinol. 2000; 85: 4231-6.
38. Vidal H, Auboeuf D, de Vos P, Staels  B, Riou JP, Auwerx  J, et al. The expression of ob gene is not acutely regulated by insulin and fasting in human abdominal subcutaneous adipose tissue. J Clin Invest. 1996; 98: 251-5.
39. Wang  J, Chinookoswong N, Scully S, Qi M, Shi ZQ. Differential effects of leptin in regulation of tissue glucose utilization in vivo. Endocrinology. 1999; 140: 2117-24.
40. Hidaka S, Yoshimatsu H, Kondou  S, Tsuruta  Y, Oka K, Noguchi H, et al. Chronic central leptin infusion restores hyperglycemia independent of food intake and insulin level in streptozotocin-induced diabetic rats. FASEB J. 2002; 16: 509-18.
41. Grasso P, Rozhavskaya- A, Leinung  MC, Lee  DW. D-Leu-4- OB3, a synthetic leptin agonist, improves hyperglycemic control in C57BL/6jJ ob/ob mice. Regul Pept. 2001; 101: 123-9.
42. Poveda  E, Lareo L. Diseño teorico de péptidos miméticos de leptina diseñados por computador y postulados como farmacóforos potenciales para tratamiento de obesidad. Lecturas sobre Nutrición 2001; 3: 40-52.
43. Fong  TM, Huang RR, Tota  MR, Mao C, Smith T, Varnerin JVV, et al. Localization of leptin binding domain in the leptin receptor. Mol Pharmacol. 1998; 53: 234-40.
44. Sarin  VK, Kent SB, Tam  JP, Merrifield RB. Quantitative monitoring of solid-phase peptide synthesis by the ninhydrin reaction. Anal Biochem. 1981; 117: 147-57.
45. Guzman F, Barberis S, Lllanes  A. Peptide synthesis: chemical or enzymatic. Electronic Journal of Biotechnology. 2007; 10: 279-314. Consultado: mayo 7 de 2007. Disponible en: http://www.ejbiotechnology.info/content/vol10/issue2/full/13/13.pdf.
46. Santovena  A, Oliva A, Guzman F, Patarroyo  ME, Llabres M, Fariña JB. Chromatographic characterization of synthetic peptides: SPf66 malaria vaccine. J Chromatog B Analyt Technol Biomed Life Sci. 2002; 766: 3-12.
47. Noya O, Patarroyo  ME, Guzmán  F, Alarcón de Noya B. Immunodiagnosis of parasitic diseases with synthetic peptides. Curr Protein Pept Sci. 2003; 4: 299-308.
48. Khanam  R, Pillai  KK. Effect of chromium picolinate on modified forced swimming test in diabetic rats: involvement of serotonergic patways and potassium channels. Basic Clin Pharmacol Toxicol. 2006; 98: 155-9.
49. Cha  MC, Jones  PJ. Dietary fat type and energy restriction interactively influence plasma leptin concentration in rats. J Lipid Res. 1998; 39: 1655-60.
50. Steinberg  GR, Dyck  DJ. Development of leptin resistance in rat soleus Muscle in response to high-fat diets. Am J Physiol Endocrinol Metab. 2000; 279: E1374-82.
51. Lu H, Duanmu  Z, Houck  C, Jen KL, Buison  A, Dunbar JC. Obesity due to high fat diet decreases the sympathetic nervous and cardiovascular responses to intracerebroventricular leptin in rats. Brain Res Bull. 1998; 47: 331-5.
52. Ainslie DA, Proietto J, Fam  BC, Thorburn AW. Short-term, high-fat diets lower circulating leptin concentrations in rats. Am J Clin Nutr. 2000; 71: 438-42.
53. Eiden  S, Preibisch G, Schmidt I. Leptin responsiveness of juvenile rats: proof of leptin function within the physiological range. J Physiol. 2001; 530: 131-9.
54. Tulipano  G, Vergini AV, Soldi  D, Muller EE, Cochi D. Characterization of the resistance to the anorectic and endocrine effects of leptin in obesity-prone and obesity-resistant fed a high-fat diet. J Endocrinol. 2004; 183: 289-98.
55. Otukonyong  EE, Dube  MG, Torto R, Kalra  PS, Kalra SP. High-fat diet-induced ultradian leptin and insulin hypersecretion are absent in obesity-resistant rats. Obes Res. 2005; 13: 991-9.
56. Archer ZA, Rayner DV, Rozman  J, Klingenspor M, Mercer JG. Normal distribution of body weight gain in male Sprague-Dawley rats fed a high-energy diet. Obes Res. 2003; 11: 1376-83.
57. Jang I, Hwang  D, Lee J, Chae K, Kim Y, Kang  T, et al. Physiological difference between dietary obesity-susceptible and obesity-resistant Sprague Dawley rats in response to moderate high fat diet. Exp Anim. 2003; 52: 99-107.
58. Otukonyong EE, Dube MG, Torto  R, Kalra  PS, Kalra  SP. High-fat diet-induced ultradian leptin and insulin hypersecretion are absent in obesity-resistant rats. Obes Res. 2005; 13: 991-9.
59. Huang  BW, Chiang  MT, Yao  HT, Chiang  W. The effect of high-fat and high-fructose diets on glucose tolerance and plasma lipid and leptin levels in rats. Diabetes Obes Metab. 2004; 6: 120-6.
60. Buetnner R, Newgard CB, Rhodes  CJ, ODoherty RM. Correction of diet-induced hyperglycemia, hyperinsulinemia, and skeletal muscle insulin resistance by moderate hyperleptinemia. Am J Physiol Endocrinol Metab. 2000; 278: E563-9.
61. Oliveira VX Jr, Fazio MA, Miranda  MT, da Silva  JM, Bittencourt JC, Elias CF, et al. Leptin fragments induce Fos immunoreactivity in rat hypothalamus. Regul Pept. 2005; 127: 123-32.
62. Clegg  DJ, Riedy  CA, Smitk  K, Benoit SC, Woods  SC. Differential sensitivity to central leptin and insulin in male and female rats. Diabetes. 2003; 52: 682-7.
63. Matsuo  T, Iwashita S, Komuro  M, Suzuki  M. Effects of high-fat diet intake on glucose uptake in central and peripheral tissues of non-obese rats. J Nutr Sci Vitaminol (Tokyo). 1999; 45: 667-73.
64. Langouche L, van den Berghe G. Glucose metabolism and insulin therapy. Crit Care Clin. 2006; 22: 119-29.
How to Cite
1.
Poveda E, Trujillo P, Ruiz F, Lopez E. Glucose and insulin levels in Wistar rats submitted to high fat diet and treatment with mimetic leptin peptides. Biomed. [Internet]. 2008 Mar. 1 [cited 2024 Jul. 27];28(1):50-63. Available from: https://revistabiomedica.org/index.php/biomedica/article/view/108
Published
2008-03-01
Section
Original articles

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