Prolactin Receptor Signaling Is Essential for Perinatal Brown Adipocyte Function: A Role for Insulin-like Growth Factor-2

BACKGROUND: The lactogenic hormones prolactin (PRL) and placental lactogens (PL) play central roles in reproduction and mammary development. Their actions are mediated via binding to PRL receptor (PRLR), highly expressed in brown adipose tissue (BAT), yet their impact on adipocyte function and metabolism remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: PRLR knockout (KO) newborn mice were phenotypically characterized in terms of thermoregulation and their BAT differentiation assayed for gene expression studies. Derived brown preadipocyte cell lines were established to evaluate the molecular mechanisms involved in PRL signaling on BAT function. Here, we report that newborn mice lacking PRLR have hypotrophic BAT depots that express low levels of adipocyte nuclear receptor PPARgamma2, its coactivator PGC-1alpha, uncoupling protein 1 (UCP1) and the beta3 adrenoceptor, reducing mouse viability during cold challenge. Immortalized PRLR KO preadipocytes fail to undergo differentiation into mature adipocytes, a defect reversed by reintroduction of PRLR. That the effects of the lactogens in BAT are at least partly mediated by Insulin-like Growth Factor-2 (IGF-2) is supported by: i) a striking reduction in BAT IGF-2 expression in PRLR KO mice and in PRLR-deficient preadipocytes; ii) induction of cellular IGF-2 expression by PRL through JAK2/STAT5 pathway activation; and iii) reversal of defective differentiation in PRLR KO cells by exogenous IGF-2. CONCLUSIONS: Our findings demonstrate that the lactogens act in concert with IGF-2 to control brown adipocyte differentiation and growth. Given the prominent role of brown adipose tissue during the perinatal period, our results identified prolactin receptor signaling as a major player and a potential therapeutic target in protecting newborn mammals against hypothermia

Clinical and biochemical markers of risk in uncomplicated severe acute malnutrition

International audienceUse of mid–upper arm circumference (MUAC) as a single screening tool for severe acute malnutrition (SAM) assumes that children with a low weight-for-height z score (WHZ) and normal MUAC have lower risks of morbidity and mortality. However, the pathophysiology and functional severity associated with different anthropometric phenotypes of SAM have never been well characterized. We compared clinical characteristics, biochemical features, and health and nutrition histories of nonedematous children with SAM who had (1) low WHZ only, (2) both low WHZ and low MUAC, or (3) low MUAC only. In Bangladesh, Burkina Faso, and Liberia, we conducted a multicentric cohort study in uncomplicated, nonedematous children with SAM and low MUAC only (n = 161), low WHZ only (n = 138), or a combination of low MUAC and low WHZ (n = 152). Alongside routine anthropometric measurements, we collected a wide range of critical indicators of clinical and nutritional status and viability; these included serum leptin, an adipocytokine negatively associated with mortality risk in SAM. Median leptin levels at diagnosis were lower in children with low WHZ only (215.8 pg/mL; P < .001) and in those with combined WHZ and MUAC deficits (180.1 pg/mL; P < .001) than in children with low MUAC only (331.50 pg/mL). The same pattern emerged on a wide range of clinical indicators, including signs of severe wasting, dehydration, serum ferritin levels, and caretaker-reported health deterioration, and was replicated across study sites. Illustrative of the likely heterogeneous functional severity of the different anthropometric phenotypes of SAM, our results confirm the need to retain low WHZ as an independent diagnostic criterion

Childhood Obesity

In March 2004 a group of 65 physicians and other health professionals representing nine countries on four continents convened in Israel to discuss the widespread public health crisis in childhood obesity. Their aim was to explore the available evidence and develop a consensus on the way forward. The process was rigorous, although time and resources did not permit the development of formal evidence-based guidelines. In the months before meeting, participants were allocated to seven groups covering prevalence, causes, risks, prevention, diagnosis, treatment, and psychology. Through electronic communication each group selected the key issues for their area, searched the literature, and developed a draft document. Over the 3-d meeting, these papers were debated and finalized by each group before presenting to the full group for further discussion and agreement. In developing a consensus statement, this international group has presented the evidence, developed recommendations, and provided a platform aimed toward future corrective action and ongoing debate in the international community

Hormonal Determinants of Growth and Weight Gain in the Human Fetus and Preterm Infant

The factors controlling linear growth and weight gain in the human fetus and newborn infant are poorly understood. We review here the changes in linear growth, weight gain, lean body mass, and fat mass during mid- and late gestation and the early postnatal period in the context of changes in the secretion and action of maternal, placental, fetal, and neonatal hormones, growth factors, and adipocytokines. We assess the effects of hormonal determinants on placental nutrient delivery and the impact of preterm delivery on hormone expression and postnatal growth and metabolic function. We then discuss the effects of various maternal disorders and nutritional and pharmacologic interventions on fetal and perinatal hormone and growth factor production, growth, and fat deposition and consider important unresolved questions in the field

Screening for Metabolic and Reproductive Complications in Obese Children and Adolescents

Childhood obesity is associated with a number of metabolic comorbidities. These include glucose intolerance and type 2 diabetes mellitus, hyperlipidemia, fatty liver disease, and reproductive complications, such as polycystic ovary syndrome. The occurrence of these complications in a child or adolescent may result in progressive health decline at an early age. We, therefore, advocate screening and early diagnosis. This purpose of this review is to outline a rational, evidence-based approach to screening obese children and adolescents for metabolic and reproductive complications. In each section, the aim is to provide the primary care provider with a review of the literature supporting current screening practices. As such, this review is designed to assist the primary care provider in the selection and interpretation of screening tests and to make recommendations regarding the referral of patients for subspecialty care