Absence of Anorectic Effect to Acute Peripheral Leptin Treatment in Adult Rats whose Mothers Were Malnourished during Lactation

Abstract

Diets with restricted energy or protein during lactation programs body weight in the adult offspring. We have investigated the hypothesis that protein or energy-restricted diets during lactation alter the feeding response to peripheral leptin treatment of the adult offspring. Five Wistar rats were randomly assigned to one of the following groups on the day that the offspring were born: C, control diet with 23 % protein; PR, protein restricted diet with 8 % protein; and ER, energy-restricted, receiving the control diet in restricted quantities, which were calculated according to the mean ingestion of the PR group. After weaning (day 21), two animals from each litter (10 pups in each group) were randomly selected and placed together in the cage with free access to water and standard diet until 150 days of age, when they were tested for its response to either leptin (0.5 mg/kg body wt ip) for groups Clep, PRlep and ERlep or saline vehicle for groups Csal, PRsal and ERsal on food intake. In the control groups, food intake was reduced two hours (36 %), four hours (41 %) and six hours (25 %) after leptin treatment. In contrast, no response was observed to leptin treatment in the PRlep and ERlep groups, suggesting leptin resistance. We demonstrated the development of resistance to the anorectic leptin effect and its program in a critical life period associated to nutritional and hormonal factors.

Protein · Energy malnutrition · Leptin resistance · Lactation

References

• 1 Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman J M. Positional cloning of the mouse obese and its human homologue.  Nature. 1994;  372 425-432
• 2 Tartaglia L A, Dembski M, Weng X, Deng N, Culpepper J, Devos R, Richards G J, Campfield L A, Clark F T, Deeds J. Identification and expression cloning of a leptin receptor OB-R.  Cell. 1995;  83 1263-1271
• 3 Lee G H, Proenca R, Montez J M, Carroll K M, Darvishzadeh J G, Lee J I, Friedman J M. Abnormal splicing of the leptin receptor in diabetic mice.  Nature. 1996;  379 632-635
• 4 Schwartz M W, Seeley R J, Campfield L A, Burn P, Baskin D G. Identification of targets of leptin action in rat hypothalamus.  J Clin Invest. 1996;  98 1101-1106
• 5 Pelleymounter M A, Cullen M J, Baker M B, Hecht R, Winters D, Boone T, Collins F. Effects of the obese gene product on body weight regulation in ob/ob mice.  Science. 1995;  269 540-543
• 6 Campfield L A, Smith F J, Guisez Y, Devos R, Burn P. Recombinant mouse OB protein: evidence for a peripheral signal linking adiposity and central neural networks.  Science. 1995;  269 546-549
• 7 Friedman J M, Halaas J L. Leptin and the regulation of body weight in mammals.  Nature. 1998;  395 763-770
• 8 Senaris R, Garcia-Caballero T, Casabiell X, Callero R, Castro R, Considine R V, Dieguez C, Casanuera F F. Synthesis of leptin in human placenta.  Endocrinology. 1997;  138 4501-4504
• 9 Bado A, Levasseur S, Attoub S, Kermongant S, Laigneau J P, Bortoluzzi M N, Moizo L, Lehy T, Guerre-Millo M, Le Marchand-Brustel Y, Lewin M J. The stomach is a source of leptin.  Nature. 1998;  394 790-793
• 10 Wang J, Liu R, Hawkins M, Barzilai N, Rossetti L. A nutrient-sensing pathway regulates leptin gene expression in muscle and fat.  Nature. 1998;  393 684-688
• 11 Smith-Kirwin SM, O’Connor D M, De Johnston J, De Lancey E D, Hassink S G, Funanage V L. Leptin expression in human mammary epithelial cells and breast milk.  J Clin Endocrinol Metab. 1998;  83 1810-1813
• 12 Morash B, Li A, Murphy P R, Wilkinson M, Ur E. Leptin gene expression in the brain and pituitary gland.  Endocrinology. 1999;  1140 5995-5998
• 13 Jin L, Burguera B G, Couce M E, Scheithauer B W, Lamson J, Eberhardt N L, Kulig E, Lloyd R V. Leptin and leptin receptor expression in the normal and neoplastic human pituitary: evidence of a regulatory role of leptin on pituitary cell proliferation. J Clin Endocrinol.  Metab. 1999;  84 2903-2911
• 14 Jin L, Zhang S, Burguera B G, Couce M E, Osamura R Y, Kulig E, Lloyd R. Leptin and leptin receptor expression in rat and mouse pituitary cells.  Endocrinology. 2000;  141 333-339
• 15 Banks W A, Kastin A J, Huang W, Jaspan J B, Maness L M. Leptin enters the brain by a saturable system independent of insulin.  Peptides. 1996;  17 305-311
• 16 Hwa J J, Fawzi A B, Graziano M P, Ghibaudi L, Williams P, van Heek M, Davis H, Rudinski M, Sybertz E, Strader C D. Leptin increases energy expenditure and selectively promotes fat metabolism in ob/ob mice.  Am J Physiol Regulatory Integrative Comp Physiol. 1997;  272 1204-1209
• 17 Chua S C , Chung W K, Wu-Peng X S, Zhang Y, Liu S M, Tartaglia L, Leibel R L. Phenotypes of mouse diabetes and rat fatty due to mutations in the OB (leptin) receptor.  Science. 1996;  271 994-996
• 18 Tartaglia L A. The leptin receptor.  J Biol Chem. 1997;  272 6093-6096
• 19 Considine R V, Sinha M K, Heiman HML. et al . Serum immunoreactive-leptin concentrations in normal-weight and obese humans.  N Engl J Med. 1996;  334 292-295
• 20 Maffei M, Halaas J, Ravussin E, Pratley R E, Lee G H, Zhang Y, Fei H, Kim S, Lallone R, Ranganathan S. Leptin levels in human and rodent: Mensurament of plasma leptin and ob RNA in obese weight-reduced subjects.  Nat Med. 1995;  1 1155-1161
• 21 Van Heek M, Compton D S, France C F, Tedesco R P, Fawzi A B, Graziano M P, Sybertz E J, Strader C D, Davis H R Jr. Diet-induced obese mice develop peripheral but not central resistance to leptin.  J Clin Invest. 1997;  99 385-390
• 22 Lin L, York D A. Chronic ingestion of dietary fat is a prerequisite for inhibition of feeding by enterostatin.  Am J Physiol Regulatory Integrative Comp Physiol. 1998;  275 619-623
• 23 Martin R L, Perez E, He Y J, Dawson R, Millard W J. Leptin resistance is associated with hypothalamic leptin receptor mRNA and protein downregulation.  Metabolism. 2000;  49 1479-1484
• 24 Passos M CF, Ramos C, Moura E G. Short and long term effects of malnutrition in rats during lactation on the body weight of offspring.  Nutrition Research. 2000;  20 1603-1612
• 25 Teixeira C V, Passos M CF, Ramos C F, Dutra S CP, Moura E G. Leptin serum concentration in rats whose mothers were submitted to malnutrition during lactation.  Journal of Nutritional Biochemistry. 2002;  13 493-498
• 26 Bayne K. Revised Guide for the Care and Use of Laboratory Animals available.  Am Phy Soc Physiol. 1996;  39 208-211
• 27 Reeves P G, Nielsen F H, Fahey G C. AIN-93 Purified diets for laboratory rodents: final report of the American Institute of Nutrition Ad Hoc Writing Commitee on the reformulation of the AIN-76 rodent diet.  J Nutr. 1993;  123 1939-1951
• 28 Fishbeck K L, Rasmussen K M. Effect of repeated cycles on maternal nutritional status, lactational performance and litter growth in ad libitum-fed and chronically food-restricted rats.  J Nutr. 1987;  117 1967-1975
• 29 Lin L, Martin A, Schaffhauser O, York D A. Acute changes in the response to peripheral leptin with alteration in the diet composition.  Am J Physiol Regulatory Integrative Comp Physiol. 2001;  280 504-509
• 30 Zar J H. Biostatistical analysis, 4th ed. Upper Saddle River; Prentice-Hall 1999
• 31 Lin S, Storlien L H, Huang X. Leptin receptor, NPY, POMC mRNA expression in the diet-induced obese mouse brain.  Brain Research. 2000;  875 89-95
• 32 Vila R, Adan C, Rafecas I, Fernandez-Lopez J A, Remesar X, Alemany M.
  Plasma leptin turnover rates in lean and obese Zucker rats.  Endocrinology. 1998;  139 4466-4469
• 33 Cravo C O, Teixeira C V, Passos M C, Dutra S C, de Moura E G, Ramos C. Leptin treatment during the neonatal period is associated with higher food intake and adult body weight in rats.  Horm Metab Res. 2002;  34 400-405
• 34 Passos M CF, Ramos C F, Dutra S CP, Mouço T, Moura E G. Long-term effects of malnutrition during lactation on the thyroid function of offspring.  Hormone Metabolic Research. 2002;  34 40-43
• 35 Teixeira C V, Ramos C DF, Mouço T, Passos M CF, Moura E G. Leptin injection during lactation alters thyroid function in adult rats.  Hormone Metabolic Research. 2003;  35 367-371
• 36 Barker D J. The fetal and infant origins of disease.  Eur J Clin Invest. 1995;  25 457-463
• 37 Waterland R A, Garza C. Potencial mechanisms of metabolic imprinting that leads to chronic disease.  Am J Clin Nutr. 1999;  69 179-197
• 38 Chang G Q, Benyaminova L, Libowitz S F. Dietary fat reduces expression of the leptin receptor, ob-R, in hypothalamic paraventricular (PVN) and arcuate (ARC) nuclei.  Society for Neuroscience. 1999;  25 414-419