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Neonatal leptin treatment programmes leptin hypothalamic resistance and intermediary metabolic parameters in adult rat

Published online by Cambridge University Press:  08 March 2007

Fabiane Pereira Toste
Affiliation:
Department of Physiological Sciences, Institute of Biology, State University of Rio de Janeiro, 20550-030, Rio de Janeiro, Brazil
Egberto Gaspar de Moura
Affiliation:
Department of Physiological Sciences, Institute of Biology, State University of Rio de Janeiro, 20550-030, Rio de Janeiro, Brazil
Patrícia Cristina Lisboa
Affiliation:
Department of Physiological Sciences, Institute of Biology, State University of Rio de Janeiro, 20550-030, Rio de Janeiro, Brazil
Aline Teixeira Fagundes
Affiliation:
Department of Physiological Sciences, Institute of Biology, State University of Rio de Janeiro, 20550-030, Rio de Janeiro, Brazil
Elaine de Oliveira
Affiliation:
Department of Physiological Sciences, Institute of Biology, State University of Rio de Janeiro, 20550-030, Rio de Janeiro, Brazil
Magna Cottini Fonseca Passos*
Affiliation:
Department of Physiological Sciences, Institute of Biology, State University of Rio de Janeiro, 20550-030, Rio de Janeiro, Brazil Department of Applied Nutrition, Nutrition Institute, State University of Rio de Janeiro, 20550-030, Rio de Janeiro, Brazil
*
*Corresponding author: Professor Magna Cottini Fonseca Passos, fax +5 21 25876129, email magna@uerj.br
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Abstract

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We previously showed that neonatal leptin treatment programmes higher body weight and food intake in adult rats. Here we investigate whether leptin treatment during lactation affects the anorectic effect of leptin on adult rats and their hypothalamic leptin receptors (OB-Rb) and whether those changes could have consequences on intermediary metabolism. When the offspring were born, pups were divided into two groups: the Lep group, injected daily with leptin (8μg/100g body weight, subcutaneously) for the first 10d of lactation, and the control group, injected daily with saline. After weaning (day 21), body weight and food intake were monitored until the rats were 150d old. Food intake was higher in the Lep group (approximately 14%, p<0·05) from day 133 onwards, and body weight was higher (approximately 10%, p<0·05) from day 69 onwards, compared with the control group. At 150d of age, the rats were tested for food intake in response to either leptin (05mg/kg body weight intraperitoneally; groups CL and LepL) or saline (groups CSal and LepSal). The CL group showed a decrease in food intake, but no response was observed in the LepL group, suggesting leptin resistance. The Lep group demonstrated a decrease in OB-Rb expression (−40% p<0·05), hyperleptinaemia (+78%, p<0·05), hyperinsulinaemia (+100%, p<0·02), hypertriacylglycerolaemia (+17%, p<0·05) and a higher protein content in the body (+16%, p<0·05) without changes in fat mass and glycaemia. We conclude that neonatal leptin treatment programmes both hyperleptinaemia and hyperinsulinaemia in adulthood, which leads to leptin resistance by reducing the expression of the hypothalamic leptin receptor.

Type
Research Article
Copyright
Copyright © The Nutrition Society 2006

References

Ahima, RS, Prabakaran, D & Flier, JSPostnatal leptin surge and regulation of circadian rhythm of leptin by feeding. J Clin Invest (1998) 101, 10201027.CrossRefGoogle ScholarPubMed
Ahima, RS, Saper, CB, Flier, JS & Elmquist, JKLeptin regulation of neuroendocrine systems. Front Neuroendocrinol (2000) 21, 263307.CrossRefGoogle ScholarPubMed
Bayne, KRevised Guide for the Care and Use of Laboratory Animals available. Am Phys Soc Physiol (1996) 39, 208211.Google ScholarPubMed
Bradford, MMA rapid and sensitive method for the quantification of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem (1976) 72, 248254.CrossRefGoogle Scholar
Campfield, LA, Smith, FJ, Guisez, Y, Devos, R & Burn, PRecombinant mouse OB protein: evidence for a peripheral signal linking adiposity and central neural networks. Science (1995) 269, 546549.CrossRefGoogle ScholarPubMed
Carbo, N, Ribas, VV, Busquets, S, Alvarez, B, Lopez-Soriano, FJ & Argiles, JMShort-term effects of leptin on skeletal muscle protein metabolism in the rat. J Nutr Biochem (2000) 11, 431435.CrossRefGoogle ScholarPubMed
Casabiell, X, Piñeiro, V, Tomé, MA, Peinó, R, Diéguez, C & Casanueva, FFPresence of leptin in colostrum and/or breast milk from lactating mothers: a potential role in the regulation of neonatal food intake. J Clin Endocr Metab (1997) 82, 42704273.CrossRefGoogle ScholarPubMed
Casanueva, FF & Dieguez, CInteraction between body composition, leptin and growth hormone status. Baillieres Clin Endocrinol Metab (1998) 12, 297314.CrossRefGoogle ScholarPubMed
Ceddia, RB, William, WN Jr & Curi, RThe response of skeletal muscle to leptin. Front Biosci (2001) 6, 9097.CrossRefGoogle ScholarPubMed
Chan, YY, Steiner, RA & Clifton, DKRegulation of hypothalamic neuropeptide-Y neurons by growth hormone in the rat. Endocrinology (1996) 137, 13191325.CrossRefGoogle ScholarPubMed
Cravo, CO, Teixeira, CV, Passos, MC, Dutra, SC, Moura, EG & Ramos, CLeptin treatment during the neonatal period is associated with higher food intake and adult body weight in rats. Horm Metab (2002) 34, 400405.CrossRefGoogle Scholar
Dorner, G & Plagemann, APerinatal hyperinsulinism as possible predisposing factor for diabetes mellitus, obesity and enhanced cardiovascular risk in later life. Horm Metab Res (1994) 26, 213221.CrossRefGoogle ScholarPubMed
Elias, CF, Aschkenasi, C, Lee, C, Kelly, J, Ahima, RS, Bjorbaek, C, Flier, JSSaper, CB & Elmquist, JKLeptin differentially regulates NPY and POMC neurons projecting to the lateral hypothalamic area. Neuron (1999) 23, 775786.CrossRefGoogle Scholar
Fishbeck, KL & Rasmussen, KMEffect 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, 19671975.CrossRefGoogle Scholar
Friedman, JM & Halaas, JLLeptin and the regulation of body weight in mammals. Nature (1998) 395, 763770.CrossRefGoogle ScholarPubMed
Hegyi, K, Fülöp, KA, Kovács, KJ, Falus, A & Tóth, SHigh leptin level is accompanied with decreased long leptin receptor transcript in histamine deficient transgenic mice. Immunol Letts (2004) 92, 193197.CrossRefGoogle ScholarPubMed
Houseknecht, kl, McGuire, MK, Portocarrero, CP, McGuire, MA & Beerman, KLeptin is present in human milk and is related to maternal plasma leptin concentration and adiposity. Biochem Biophys Res Commun (1997) 240, 742747.CrossRefGoogle ScholarPubMed
JE, Leptin signaling, adiposity, and energy balance. Ann N Y Acad Sci (2002) 967, 379388.Google Scholar
Kieffer, TJ & Habener, JFThe adipoinsular axis: effects of leptin on pancreatic beta-cells. Am J Physiol (2000) 278, E1E14.Google ScholarPubMed
Kim, YB, Uotani, S, Pierroz, DD, Flier, JS & Kahn, BBIn vivo administration of leptin activates signal transduction directly in insulin-sensitive tissues: overlapping but distinct pathways from insulin. Endocrinolology (2000) 141, 23282339.CrossRefGoogle ScholarPubMed
Leshner, AL & Litwin, VAA simple method for carcass analysis. Physiol Behav (1972) 9, 282289.CrossRefGoogle ScholarPubMed
Levin, BE, Dunn-Meynell, AA, Ricci, MR & Cummings, DEAbnormalities of leptin and ghrelin regulation in obesity-prone juvenile rats. Am J Physiol Endocrinol Metab (2003) 285, 949957.CrossRefGoogle ScholarPubMed
Lin, L, Martin, A, Schaffhauser, O & York, DAAcute changes in the response to peripheral leptin with alteration in the diet composition. Am J Physiol Regul Integr Comp Physiol (2001) 280, 504509.CrossRefGoogle ScholarPubMed
Lin, L & York, DAChronic ingestion of dietary fat is a prerequisite for inhibition of feeding by enterostatin. A Am J Physiol Regul Integr Comp Physiol (1998) 275, 619623.CrossRefGoogle ScholarPubMed
Lowry, OH, Rosebrough, NJ, Farr, AL & Randall, RJProtein measurement with the Folin phenol reagent. J Biol Chem (1951) 193, 265275.CrossRefGoogle ScholarPubMed
Madiehe, AM, Schalfhauser, AO, Braymer, DH, Bray, GA & York, DADifferential expression of leptin receptor in high and low-fat-fed Osborne-Mendel and S5B/Pl rats. Obes Res (2000) 8, 467474.CrossRefGoogle ScholarPubMed
Malendowicz, LK, Macchi, C, Nussdorfer, GG & Nowak, KWAcute effects of recombinant murine leptin on rat pituitary-adrenocortical function. Endocr Res (1998) 24, 235246.CrossRefGoogle ScholarPubMed
Mantzoros, CS, Varvarigou, A, Kaklamani, VG, Beratis, NG & Flier, JSEffect of birth weight and maternal smoking on cord blood leptin concentrations of full-term and preterm newborns. J Clin Endocrinol Metab (1997) 82, 28562861.Google ScholarPubMed
Marks, JL, Porte, D Jr, Stahl, WL & Baskin, DGLocalization of insulin receptor mRNA in rat brain by in situ hybridization. Endocrinology (1990) 127, 32343236.CrossRefGoogle ScholarPubMed
Maroni, P, Bendinelli, P & Piccoletti, REarly intracellular events induced by in vivo leptin treatment in mouse skeletal muscle. Mol Cell Endocrinol (2003) 201, 109121.CrossRefGoogle ScholarPubMed
Martin, RL, Perez, E, He, YJ, Dawson, R & Millard, WJLeptin resistance is associated with hypothalamic leptin receptor mRNA and protein downregulation. Metabolism (2000) 49, 14791484.CrossRefGoogle ScholarPubMed
Mistry, AM, Swick, A & Romsos, DRLeptin alters metabolic rates before acquisition of its anorectic effect in developing neonatal mice. Am J Physiol Journal Physiology (1999) 46, 742747.Google Scholar
Muller, G, Ertl, J, Gerl, M & Preibisch, GLeptin impairs metabolic actions of insulin in isolated rat adipocytes. J Biol Chem (1997) 272, 1058510593.CrossRefGoogle ScholarPubMed
Niswender, KD, Baskin, DG & Schwartz, MWInsulin and its evolving partnership with leptin in the hypothalamic control of energy homeostasis. Trends Endocrinol Metab (2004) 15, 362369.CrossRefGoogle ScholarPubMed
Oates, M, Noodside, B & Walker, CDChronic leptin administration in developing rats reduces stress responsiveness partly through changes in maternal behavior. Horm Behav (2000) 37, 366376.CrossRefGoogle ScholarPubMed
Passos, MCF, Ramos, CF, Dutra, SCP, Mouço, T & Moura, EGLong-term effects of malnutrition during lactation on the thyroid function of offspring. Horm Metab Res (2002) 34, 4043.CrossRefGoogle ScholarPubMed
Passos, MCF, Ramos, CF & Moura, EGShort and long term effects of malnutrition in rats during lactation on the body weight of offspring. Nutr Res (2000) 20, 16031612.CrossRefGoogle Scholar
Passos, MCF, Vicente, LL, Lisboa, PC & Moura, EGAbsence of anorectic effect to acute peripheral leptin treatment in adult animals whose mothers were malnourished during lactation. Horm Metab Res (2004) 36, 625629.CrossRefGoogle ScholarPubMed
Pelleymounter, MA, Cullen, MJ, Baker, MB, Hecht, R, Winters, D, Boone, T & Collins, FEffects of the obese gene product on body weight regulation in ob/ob mice. Science (1995) 269, 540543.CrossRefGoogle ScholarPubMed
Pracyck, JB, Seidler, FJ, McCook, EC & Slotkin, TAPituitarythyroid axis reactivity to hyper- and hypothyroidism in the perinatal period: ontogeny of regulation and long term programming of responses. J Dev Physiol (1992) 18, 105109.Google Scholar
Proulx, K, Clavel, S, Nault, G, Richard, D & Walker, CDHigh neonatal leptin exposure enhances brain GR expression and feedback efficacy on the adrenocortical axis of developing rats. Endocrinology (2001) 142, 46074616.CrossRefGoogle ScholarPubMed
Sahu, ALeptin signaling in the hypothalamus: emphasis on energy homeostasis and leptin resistance. Front Neuroendocrinol (2004) 24, 225253.CrossRefGoogle Scholar
Scarpace, PJ, Matheny, M & Turner, NHypothalamic leptin resistance is associated with impaired leptin signal transduction in aged obese rats. Neuroscience (2001) 104, 11111117.CrossRefGoogle ScholarPubMed
Schwartz, MW, Seeley, RJ, Campfield, LA, Burn, P & Baskin, DGIdentification of targets of leptin action in rat hypothalamus. J Clin Invest (1996) 98, 11011106.CrossRefGoogle ScholarPubMed
Seufert, JR, Laubner, K & Jakob, FJSignaling and gene regulation by leptin in pancreatic beta-cells involves suppressor of cytokine signaling 3 (SOCS-3).82nd Annual Meeting of the Endocrine Society,Toronto, canada (abstract 1219). (2000)Google Scholar
Stansbie, DRegulation of the human pyruvate dehydrogenase complex. Clin Sci Mol Med (1976) 51, 445452.Google ScholarPubMed
Steinberg, GR & Dyck, DJDevelopment of leptin resistance in rat soleus muscle in response to high-fat diets. Am J Physiol Endocrinol Metab (2000) 279, E1374E1382.CrossRefGoogle ScholarPubMed
Tannenbaum, GS, Gurd, W & Lapointe, MLeptin is a potent stimulator of spontaneous pulsatile growth hormone (GH) secretion and the GH response to GH-releasing hormone. Endocrinology (1998) 139, 38713875.CrossRefGoogle ScholarPubMed
Teixeira, CV, Passos, MCF, Ramos, CF, Dutra, SCP & Moura, EGLeptin serum concentration in rats whose mothers were submitted to malnutrition during lactation. J Nutr Biochem (2002) 13, 493498.CrossRefGoogle ScholarPubMed
Teixeira, CV, Ramos, CDF, Mouço, T, Passos, MCF & Moura, EGLeptin injection during lactation alters thyroid function in adult rats. Horm Metab Res (2003) 35, 367371.Google ScholarPubMed
Trottier, G, Koski, KG, Brun, T, Toufexis, DJ, Richard, D & Walker, CDIncreased fat intake during lactation modifies hypothalamicpituitary- adrenal responsiveness in developing rat pups: a possible role for leptin. Endocrinology (1998) 139, 37043711.CrossRefGoogle Scholar
Unger, RH, Zhou, YT & Orci, LRegulation of fatty acid homeostasis in cells: novel role of leptin. Proc Natl Acad Sci USA (1999) 96, 23272332.CrossRefGoogle ScholarPubMed
Walker, P & Courtin, FTransient neonatal hyperthyroidism results in hypothyroidism in the adult rat. Endocrinology (1985) 116, 22462250.CrossRefGoogle ScholarPubMed
Wang, J, Liu, R, Hawkins, M, Barzilai, N & Rossetti, LA nutrient-sensing pathway regulates leptin gene expression in muscle and fat. Nature (1998) 393, 684688.CrossRefGoogle ScholarPubMed
Woods, SC, Lotter, EC, McKay, LD & Porte, D JrChronic intracerebroventricular infusion of insulin reduction reduces food intake and body weight of baboons. Nature (1979) 282, 503505.CrossRefGoogle Scholar