Leptin in Early Life: A Key Factor for the Development of the Adult Metabolic Profile

Granado, Miriam; Fuente-Martín, Esther; García‐Cáceres, Cristina; Argente, Jesús; Chowen, Julie A.

doi:10.1159/000336967

Cited by 35 publications

(30 citation statements)

References 246 publications

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“…Longer follow-up is necessary to find out whether the possible metabolic advantages of early insulin treatment persist into later childhood and adulthood. Our proposal for longer follow-up is confirmed by previous results of animal studies in which leptin or exendin-4 was administered during the neonatal period indicating that early postnatal intervention can indeed have long-term effects on metabolism [40,41]. …”

Section: Discussionsupporting

confidence: 76%

Components of the Metabolic Syndrome in Early Childhood in Very-Low-Birth-Weight Infants

Jong

Lafeber²,

Cranendonk³

et al. 2013

Horm Res Paediatr

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Background/Aims: Term small-for-gestational-age and preterm born infants have an increased prevalence of metabolic syndrome components already in childhood. Data in very-low-birth-weight (VLBW) children are limited. We investigated the prevalence of metabolic syndrome components in VLBW infants at 2 years of corrected age. Methods: We included 38 children, participating in the Neonatal Insulin Replacement Therapy in Europe (NIRTURE) trial, a randomized controlled trial of early insulin therapy in VLBW infants. Metabolic syndrome components were defined as: body mass index SDS >2; blood pressure (systolic and/or diastolic) ≥90th percentile; triglycerides ≥0.98 mmol/l; high-density lipoprotein (HDL) cholesterol ≤1.03 mmol/l; glucose ≥5.6 mmol/l. Results: Two children (5%) had three metabolic syndrome components, 13 children (34%) had two components, and 11 children (29%) one component. 63% had raised blood pressure (prevalence higher in boys), 32% low HDL, and 30% high triglycerides (prevalence lower in early insulin group). In children with body mass index SDS <0, insulin-treated children had higher HDL than children with standard care. Systolic blood pressure was correlated with growth between term and 2 years of corrected age. Conclusions: VLBW infants already have a high prevalence of metabolic syndrome components at 2 years of corrected age. Early insulin treatment could have long-term benefits for some of these components.

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Section: Discussionsupporting

confidence: 76%

Components of the Metabolic Syndrome in Early Childhood in Very-Low-Birth-Weight Infants

Jong

Lafeber²,

Cranendonk³

et al. 2013

Horm Res Paediatr

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“…It is thus highly involved in the plasticity and hardwiring of the hypothalamic appetite regulatory circuits (Bouret et al 2004). Secondly, perinatal leptin manipulation had long-term effects on offspring hypothalamus-adipose axis regulation (Granado et al 2012). Thirdly, post-natal leptin surge was modified following maternal nutrition manipulation (i.e.…”

Section: Circulating Factorsmentioning

confidence: 99%

The hypothalamus–adipose axis is a key target of developmental programming by maternal nutritional manipulation

Breton¹

2012

Journal of Endocrinology

114

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Epidemiological studies initially demonstrated that maternal undernutrition leading to low birth weight may predispose for energy balance disorders throughout life. High birth weight due to maternal obesity or diabetes, inappropriate early post-natal nutrition and rapid catch-up growth may also sensitise to increased risk of obesity. As stated by the Developmental Origin of Health and Disease concept, the perinatal perturbation of foetus/neonate nutrient supply might be a crucial determinant of individual programming of body weight set point. The hypothalamus-adipose axis plays a pivotal role in the maintenance of energy homoeostasis controlling the nutritional status and energy storage level. The perinatal period largely corresponds to the period of brain maturation, neuronal differentiation and active adipogenesis in rodents. Numerous dams and/or foetus/neonate dietary manipulation models were developed to investigate the mechanisms underlying perinatal programming in rodents. These models showed several common offspring hypothalamic consequences such as impaired neurogenesis, neuronal functionality, nuclei structural organisation and feeding circuitry hardwiring. These alterations led to a persistent reprogrammed appetite system that favoured the orexigenic pathways, leptin/insulin resistance and hyperphagia. Impaired hypothalamic sympathetic outflow to adipose tissue and/or reduced innervation may also account for modified fat cell metabolism. Thus, enhanced adipogenesis and/or lipogenesis capacities may predispose the offspring to fat accumulation. Abnormal hypothalamus-adipose axis circadian rhythms were also evidenced. This review mainly focuses on studies in rodents. It highlights hormonal and epigenetic mechanisms responsible for long-lasting programming of energy balance in the offspring. Dietary supplementation may provide a therapeutic option using a specific regimen for reversing adverse programming outcomes in humans.

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“…Leptin stimulates thermogenesis and reduces appetite, and its plasma levels are related to BMI. [17][18][19][20][21] In contrast, ghrelin levels fall with increasing BMI and directly stimulate hGH secretion 22 ; these 2 hormones have been related to Russell syndrome 23 and to anorexia nervosa.…”

Section: Discussionmentioning

confidence: 99%

The Role of Leptin in Diencephalic Syndrome

Velasco¹,

Clemente

Lorite

et al. 2014

Pediatrics

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Diencephalic syndrome is a rare condition associated with central nervous system tumors. The most common presentation is secondary failure to thrive with proper caloric intake and no statural impairment. Despite the importance of this syndrome, little is known of its pathophysiology. Some reports have documented changes in human growth hormone and insulin levels at the onset, whereas others have described endocrine disorders of hypothalamic insufficiency resulting from surgery of the tumor. It has been suggested that the hormonal changes described, such as increased human growth hormone and ghrelin or decreased insulin and leptin levels, are related to a patient’s BMI. These findings support the role of these 4 hormones as indicators of the patient’s nutritional status but not as mediators or potential therapeutic targets of the disease. We report the case of an infant who initially presented with tumor progression and, after chemotherapy, progressive weight gain and reduced tumor size. Because he presented no hormonal deficiencies or obesity after therapy, we were able to analyze his hormonal status uninfluenced by effects of metabolic treatment or excess weight. Although ghrelin and leptin levels have been related to nutritional status, our patient’s leptin levels fell when tumor size decreased and weight increased: an extraordinary finding because leptin concentration is expected to increase with weight gain. This paradoxical response suggests that leptin may be dysregulated in diencephalic syndrome or that the diencephalic astrocytoma may have had an effect on leptin secretion.

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Leptin in Early Life: A Key Factor for the Development of the Adult Metabolic Profile

Cited by 35 publications

References 246 publications

Components of the Metabolic Syndrome in Early Childhood in Very-Low-Birth-Weight Infants

Components of the Metabolic Syndrome in Early Childhood in Very-Low-Birth-Weight Infants

The hypothalamus–adipose axis is a key target of developmental programming by maternal nutritional manipulation

The Role of Leptin in Diencephalic Syndrome

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