Overexpression of placental leptin in diabetic pregnancy: a critical role for insulin.

Lepercq, J.; Caüzac, Michèle; Lahlou, Najiba; Timsit, José; Girard, Jean; Auwerx, Johan; Mouzon, Sylvie Hauguel-de

doi:10.2337/diabetes.47.5.847

Cited by 199 publications

(139 citation statements)

References 12 publications

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“…Increased leptin and LEPR expression in placenta from GDM patients have been well described [86,101]. Besides, it has been also reported an increased phosphorylation state of different proteins implicated on the initiation stage of translation, and as a result, an increased protein synthesis rate in placentas from GDM, suggesting a molecular mechanism for the observed increase in the placenta weight in GDM [86,102]. In fact, the placental dysfunction in women with GDM is also associated with increased amino acid transport [103].…”

Section: Role Of Leptin In Placentationmentioning

confidence: 95%

“…Leptin expression has been shown to be upregulated by different pregnancy hormones, such as chorionic gonadotrophin, and 17beta-estradiol, and by second messengers, such as cyclic adenosine 5′-monophosphate, mediated through MAPK and PI3K signaling pathways [83,[122][123][124][125][126]. Hyperinsulinemia in the pregnancy, probably also may regulate placental leptin production, perhaps acting as a circulating signal to control fetal homeostasis [102]. In fact, insulin is an inducer of leptin production in human placenta as shown in vivo [84], enhancing the activity of leptin promoter region [85].…”

Section: Role Of Leptin In Pregnancymentioning

confidence: 99%

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Role of leptin in female reproduction

Pérez-Pérez

Sánchez-Jiménez

Maymó

et al. 2015

Clinical Chemistry and Laboratory Medicine (CCLM)

125

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Abstract:Reproductive function is dependent on energy resources. The role of weight, body composition, fat distribution and the effect of diet have been largely investigated in experimental female animals as well as in women. Any alteration in diet and/or weight may induce abnormalities in timing of sexual maturation and fertility. However, the cellular mechanisms involved in the fine coordination of energy balance and reproduction are largely unknown. The brain and hypothalamic structures receive endocrine and/or metabolic signals providing information on the nutritional status and the degree of fat stores. Adipose tissue acts both as a store of energy and as an active endocrine organ, secreting a large number of biologically important molecules termed adipokines. Adipokines have been shown to be involved in regulation of the reproductive functions. The first adipokine described was leptin. Extensive research over the last 10 years has shown that leptin is not only an adipose tissue-derived messenger of the amount of energy stores to the brain, but also a crucial hormone/cytokine for a number of diverse physiological processes, such as inflammation, angiogenesis, hematopoiesis, immune function, and most importantly, reproduction. Leptin plays an integral role in the normal physiology of the reproductive system with complex interactions at all levels of the hypothalamic-pituitary gonadal (HPG) axis. In addition, leptin is also produced by placenta, where it plays an important autocrine function. Observational studies have demonstrated that states of leptin excess, deficiency, or resistance can be associated with abnormal reproductive function. This review focuses on the leptin action in female reproduction.

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Section: Role Of Leptin In Placentationmentioning

confidence: 95%

Section: Role Of Leptin In Pregnancymentioning

confidence: 99%

Role of leptin in female reproduction

Pérez-Pérez

Sánchez-Jiménez

Maymó

et al. 2015

Clinical Chemistry and Laboratory Medicine (CCLM)

125

View full text Add to dashboard Cite

show abstract

“…In one patient, 6 months after an insulinoma was surgically removed, insulin concentrations decreased from 16.2 to 7.6 mg/l, leptin decreased about 50 % and the patient's BMI had only decreased from 31 to 28 [45]. In diabetic pregnancies, placenta leptin mRNA and protein increased threefold to fivefold after the women were treated with insulin [46]. These observations strongly support a role for insulin in long-term regulation of leptin secretion from both adipocytes and placenta.…”

Section: Regulation Of Leptin By Insulinmentioning

confidence: 99%

Nutritional regulation of leptin in humans

Coleman

Herrmann

1999

Diabetologia

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OverviewPositional cloning of the defective gene in genetically obese ob/ob mice identified leptin as the long-sought hormone that communicates information about adipocyte metabolism to the brain [1]. Supplying leptin to genetically deficient ob/ob mice increases metabolic rate, body temperature and general activity and decreases food intake, body weight and adiposity [1±4]. Additionally, the importance of leptin to reproduction has been highlighted by the lack of sexual maturation in people who are genetically deficient in leptin [5] or the leptin receptor [6]. Although many of leptin's effects are centrally mediated, there is growing evidence that peripheral leptin receptors mediate leptin's proliferative effects on haemopoietic cells [7] and its anti-lipogenic effects on muscle and pancreatic islets [8,9].Because leptin has a critical role in regulating energy metabolism, adipose stores and body weight, questions have been raised concerning the control of leptin synthesis and secretion and the function of leptin in controlling satiety and food intake. Basal or fasting leptin values are higher in women than men, increase during the course of pregnancy and, in both healthy adults and those with Type II (non-insulindependent) diabetes mellitus, are strongly correlated with per cent body fat or BMI [10,11] and adipose tissue mass [12±15]. Despite these strong correlations, people with similar degrees of adiposity have circulating leptin concentrations that vary considerably. Thus, factors other than adipocyte size and fat content must influence leptin production. Further, the regulation of leptin's diurnal pattern of secretion is still to be explained.In this review we summarize current data, primarily from human studies, that address the nutritional controls on leptin synthesis and secretion and point out fruitful areas for future study. Excellent recent reviews should be consulted for information on the leptin receptor, other aspects of leptin's effects, and the relation of leptin to other hormones that regulate food intake and energy expenditure [16±22]. Leptin regulation by fasting, refeeding and overfeedingFasting and refeeding. During short-term energy restriction, plasma leptin concentrations decrease much more than the amount of weight or adipose tissue lost. For example, lean and obese adults who fasted for 52 to 96 h lost less than 4 % of body weight but the leptin concentrations decreased 54 to 72 % [23±25]. In careful long-term studies of lean and obese people who were either losing weight or maintaining a defined weight loss, leptin concentrations were lower during the period of loss than the period of weight maintenance at the same body composition [26]. After a 4 day fast followed by an additional 6 days of fasting during which an intravenous infusion of 5 % glucose was given, leptin increased 80 % within the first 24 h, even though glucose provided only 338 kcal/day [25]. Although it is possible that the previous 4 day fast confounded these results [27], taken together, these studies suggest that ...

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“…An increase in leptin secretion from adipocytes has been shown to be primarily dependent on glucose, with the effect of insulin being secondary [32]. In diabetic mothers, the expression of leptin mRNA and protein in placental tissue is increased [33]. Thus, the correlation between cord plasma leptin and maternal HbA 1C could be an indicator of augmented leptin production in fetal adipocytes and in placenta.…”

Section: Discussionmentioning

confidence: 96%

Increased fetal leptin in Type I diabetes mellitus pregnancies complicated by chronic hypoxia

et al. 2000

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Leptin is an adipocyte-derived hormone involved in energy metabolism and fuel homeostasis [1±3]. It could also be important in fetal development because both the leptin gene and leptin receptors are expressed in numerous fetal tissues [4,5]. In addition, leptin has been shown to stimulate fetal erythroid development and to have angiogenic activity [6,7].In term infants, cord blood leptin concentrations correlate directly with birth weight [8±11]. Maternal diabetes mellitus and pre-eclampsia are also associated with increased cord blood leptin concentrations [12±14]. It has been postulated that hypoxic conditions during pre-eclampsia augment placental production of leptin [14]. Erythropoietin (EPO), which regulates the synthesis of bone marrow progenitor cells and erythrocytes [15], is produced in the fetal liver and near term also in the kidney [15]. The main stimulator of EPO production is tissue hypoxia [15,16]. Erythropoietin has also been shown to be produced by placental trophoblast cells. Whether EPO expression in placenta is regulated by hypoxia and the proportion of placental EPO of all EPO in feto-placental circulation is not known [17]. Because EPO is not stored, plasma EPO concentrations are an indicator of the rate of EPO synthesis. Fetal plasma EPO concentrations correlate well with those of amniotic fluid EPO before labour both in normal and in abnormal pregnancies [18]. In response to moderate to severe tissue hypoxia, a sta- Diabetologia (2000) AbstractAims/hypothesis. The purpose of this study was to examine whether fetal leptin concentration correlates with severity of chronic or subchronic fetal hypoxia as indicated by increased fetal concentrations of erythropoietin in fetuses of mothers with Type I (insulin dependent) diabetes mellitus. Methods. We measured leptin and erythropoietin concentrations in cord plasma and amniotic fluid with radioimmunoassay in 25 pregnancies (gestational age 37.2 ± 1.0 weeks). Fetuses with amniotic fluid erythropoietin over 22.5 mU/ml were classified as hypoxic (n = 9) and those with amniotic fluid erythropoietin below 22.5 mU/ml (n = 16) as non-hypoxic. Results. The hypoxic fetuses had significantly higher cord leptin concentrations than non-hypoxic fetuses

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Overexpression of placental leptin in diabetic pregnancy: a critical role for insulin.

Cited by 199 publications

References 12 publications

Role of leptin in female reproduction

Role of leptin in female reproduction

Nutritional regulation of leptin in humans

Increased fetal leptin in Type I diabetes mellitus pregnancies complicated by chronic hypoxia

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