Leptin Treatment during the Neonatal Period is Associated with Higher Food Intake and Adult Body Weight in Rats

C, de Oliveira Cravo; Cv, Teixeira; Mc, Passos; Sc, Dutra; Moura, Egberto Gaspar de; Ramos, Cristiane da Fonte

doi:10.1055/s-2002-33473

Cited by 69 publications

(66 citation statements)

References 31 publications

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“…These studies emphasize that this activity is restricted to a neonatal critical period that precedes leptin regulation of food intake in adults (Bouret et al 2004). According to this, previous findings have shown that neonatal hyperleptinemia in rats promotes hypothalamic leptin resistance, overweight, and higher food intake in adulthood (De Oliveira Cravo et al 2002, Toste et al 2006.…”

Section: Discussionmentioning

confidence: 62%

Low expression of insulin signaling molecules impairs glucose uptake in adipocytes after early overnutrition

Rodrigues¹,

Souza²,

Silva³

et al. 2007

Journal of Endocrinology

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Experimental and clinical studies have demonstrated that early postnatal overnutrition represents a risk factor for later obesity and associated metabolic and cardiovascular disturbance. In the present study, we assessed the levels of glucose transporter 4 (GLUT-4), GLUT-1, insulin receptor (IR), IR substrate 1 (IRS-1), phosphatidylinositol 3-kinase (PI3K) and Akt expression, as well as insulin-stimulated glucose transport and Akt activity in adipocytes from adult rats previously raised in small litters (SL). The normal litter (NL) served as control group. We also investigated glycemia, insulinemia, plasma lipid levels, and glucose tolerance. Our data demonstrated that early postnatal overfeeding induced a persistent hyperphagia accompanied by a significant increase in body weight until 90 days of age. The SL group also presented a significant increase (w42%) in epidydimal fat weight. Blood glucose, plasma insulin, and lipid levels were similar among the animals from the SL and NL groups. While insulin-stimulated glucose uptake was approximately twofold higher in adipocytes from the NL group, no stimulatory effect was observed in the SL group. The impaired insulin-stimulated glucose transport in adipose cells from the SL rats was associated with a significant decrease in GLUT-4, IRS-1 and PI3K expression, and Akt activity. In contrast, IR and Akt expression in adipocytes was not different between the SL and NL groups. Despite these alterations, our results showed no differences in glucose tolerance test in rats raised under different feeding conditions. Our findings reinforce a potent and long-term effect of neonatal overfeeding, which can program major changes in the metabolic regulatory mechanisms.

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Section: Discussionmentioning

confidence: 62%

Low expression of insulin signaling molecules impairs glucose uptake in adipocytes after early overnutrition

Rodrigues¹,

Souza²,

Silva³

et al. 2007

Journal of Endocrinology

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“…We evidenced that adverse situations early in life, such as malnutrition , Dutra et al 2003, Fagundes et al 2007, de Moura et al 2007) and hormonal (de Oliveira Cravo et al 2002, Teixeira et al 2003, Lins et al 2005, Toste et al 2006a,b, Bonomo et al 2007) changes during lactation, could permanently affect the progeny. Maternal energy malnutrition during lactation programs for a higher body weight in adulthood; however, protein malnutrition programs for a lower body weight in the adult offspring (Passos et al 2000.…”

Section: Introductionmentioning

confidence: 72%

Prolactin inhibition at the end of lactation programs for a central hypothyroidism in adult rat

Bonomo

Lisboa²,

Passos³

et al. 2008

Journal of Endocrinology

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Malnutrition during lactation is associated with hypoprolactinemia and failure in milk production. Adult rats whose mothers were malnourished presented higher body weight and serum triiodothyronine (T 3 ). Maternal hypoprolactinemia at the end of lactation caused higher body weight in adult life, suggesting an association between maternal prolactin (PRL) level and programming of the offspring's adult body weight. Here, we studied the consequences of the maternal PRL inhibition at the end of lactation by bromocriptine (BRO) injection, a dopaminergic agonist, upon serum TSH and thyroid hormones, thyroid iodide uptake, liver mitochondrial a-glycerophosphate dehydrogenase (mGPD), liver and pituitary de-iodinase activities (D1 and/or D2), and in vitro post-TRH TSH release in the adult offspring. Wistar lactating rats were divided into BRO -injected with 1 mg/twice a day, daily for the last 3 days of lactation, and C -control, saline-injected with the same frequency. At 180 days of age, the offspring were injected with 125 I i.p. and after 2 h, they were killed. Adult animals whose mothers were treated with BRO at the end of lactation presented lower serum TSH (K51%), T 3 (K23%), and thyroxine (K21%), lower thyroid 125 I uptake (K41%), liver mGPD (K55%), and pituitary D2 (K51%) activities, without changes in the in vitro post-TRH TSH release. We show that maternal PRL suppression at the end of lactation programs a hypometabolic state in adulthood, in part due to a thyroid hypofunction, caused by a central hypothyroidism, probably due to decreased TRH secretion. We suggest that PRL during lactation can regulate the hypothalamus-pituitary-thyroid axis and programs its function.

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“…Although a wide distribution of leptin receptors has been observed in the murine fetus (24), the functional role of leptin during fetal and/or postnatal periods of development remains controversial. Investigations so far have only examined the effect of systemic leptin administration during the postnatal period (3,10,15,28,36,63). Systemic leptin administration in the postnatal rat was observed to cause a disinhibition of nonshivering thermogenesis (10), an increase in energy expenditure in a diurnal manner (4, 51), a decline in the fat pad weight (36,44,63) and body fat content (36,44), and a decrease in body weight (3,28,36,63), attesting to the presence of leptin sensitivity during this period of development.…”

mentioning

confidence: 99%

“…Investigations centered on the hypothalamic action of leptin have yielded differing results, with some studies reporting no effect, lending support to the concept of hypothalamic leptin resistance during the postnatal period (3). Other studies have demonstrated leptin-induced changes in the neuronal connectivity (11) and expression of key neuropeptides that are known to regulate ingestive behavior in the adult (36).Recent investigations have focused on postnatal systemic leptin administration having long-term effects mainly on adult male food intake and body weight (11,15). Thus whether postnatal hypothalamic leptin resistance exists is controversial.…”

mentioning

confidence: 99%

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Postnatal intracerebroventricular exposure to leptin causes an altered adult female phenotype

Varma¹,

He²,

Shin³

et al. 2004

American Journal of Physiology-Endocrinology and Metabolism

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We investigated the effect of daily intracerebroventricular (ICV) leptin administration (neonatal age 2-7 days) on hypothalamic neuropeptides (neuropeptide Y, ␣-melanocyte-stimulating hormone) that regulate food intake, body weight (BW) gain, and the metabolic/hormonal profile in suckling (8 and 21 days) and adult rat (35, 60, 90, and 120 days). ICV leptin (0.16 g ⅐ g BW Ϫ1 ⅐ dose Ϫ1 ; n ϭ 70) led to a postnatal decline in BW (P ϭ 0.0002) that persisted only in the adult females (P ϭ 0.002). The postnatal decline in BW due to leptin was associated with a decline in food intake (P ϭ 0.01) and hypothalamic leptin receptor (P ϭ 0.008) and neuropeptide Y (P ϭ 0.008) immunoreactivities and an increase in ␣-melanocyte-stimulating hormone (P ϭ 0.008) immunoreactivity. In addition, hyperinsulinemia (P ϭ 0.01) with hypocorticosteronemia (P ϭ 0.007) occurred during the postnatal period with hypercorticosteronemia (P ϭ 0.007) and hypoleptinemia (P ϭ 0.008) and an increase in leutinizing hormone (P ϭ 0.01) in the adult male and female progeny. Persistent hyperinsulinemia (P ϭ 0.015) with hyperglycemia (P ϭ 0.008) and glucose intolerance (P ϭ 0.001) were observed only in the adult female. We conclude that postnatal leptin administration alters the adult female phenotype and speculate that this may relate to retention of leptin sensitivity resulting in a lipoatrophic state. development; ob gene; food intake; hyperinsulinemia; neuropeptide Y LEPTIN, THE TRANSLATED AND SECRETED PRODUCT of the ob gene (65), is primarily synthesized by adipose tissue (25), interacts with membrane-associated leptin receptors in various tissues (13,24,54), and regulates energy homeostasis by matching rates of energy expenditure with energy intake (25,42,45,46,61).The biological actions of leptin are composed of direct peripheral (on target organs) and central (via hypothalamic and sympathetic nervous system) effects. Peripherally, leptin affects the metabolism of various tissues including the pancreatic ␤-islets (30, 66), adipocytes (38, 42), skeletal muscle (50, 62), and liver (41), thereby modulating insulin secretion and sensitivity (30,41,42,50,62,66). Centrally, leptin traverses the blood-brain barrier via receptor-mediated transcytosis (ObRa) or, in the absence of a blood-brain barrier, directly accesses the intracellular signal-transducing long isoform of the leptin receptor (ObRb) expressed in the hypothalamus (2,6,8,54). In the hypothalamus, leptin alters the synthesis and release of key orexigenic (neuropeptide Y, agouti-related peptide) and anorexigenic (proopiomelanocortin and cocaine and amphetamine-related transcript) peptides in the adult, thereby suppressing appetite resulting in anorexia, increasing sympathetic nervous output resulting in enhanced energy expenditure, and ultimately producing weight loss (16,46,61).Although most of the studies involving leptin action have been reported in the adult, some information during the postnatal period exists. Circulating leptin concentrations peak in the suckling mouse at age 7-10 days and ...

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Leptin Treatment during the Neonatal Period is Associated with Higher Food Intake and Adult Body Weight in Rats

Cited by 69 publications

References 31 publications

Low expression of insulin signaling molecules impairs glucose uptake in adipocytes after early overnutrition

Low expression of insulin signaling molecules impairs glucose uptake in adipocytes after early overnutrition

Prolactin inhibition at the end of lactation programs for a central hypothyroidism in adult rat

Postnatal intracerebroventricular exposure to leptin causes an altered adult female phenotype

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