Steroid-Dependent Up-Regulation of Adipose Leptin Secretion In Vitro During Pregnancy in Mice1

Kronfeld‐Schor, Noga; Zhao, Jing; Silvia, Brian A.; Bicer, Elad; Mathews, Patrick T.; Urban, Renata R.; Zimmerman, Stefan L.; Kunz, Thomas; Widmaier, Eric P.

doi:10.1095/biolreprod63.1.274

Cited by 43 publications

(41 citation statements)

References 47 publications

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“…In contrast, some studies have failed to detect the presence of leptin in the rat placenta (8) and in rodents, unlike humans, the placenta may not be the major source of maternal leptin production (7). Indeed, in mice, hyperleptinaemia during pregnancy primarily results from corticosterone-dependent up-regulation of leptin secretion from adipose tissue (50). The present study demonstrated protein expression of leptin and ObR-S in the rat placenta near term (day 21, term is 23 days) and demonstrates that placental leptin expression is responsive to glucocorticoid status.…”

Section: Discussionsupporting

confidence: 54%

Maternal glucocorticoid treatment modulates placental leptin and leptin receptor expression and materno-fetal leptin physiology during late pregnancy, and elicits hypertension associated with hyperleptinaemia in the early-growth-retarded adult offspring

Sugden

Langdown²,

Munns³

et al. 2001

European Journal of Endocrinology

120

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Background: Leptin concentrations are increased during late pregnancy, and leptin receptors are expressed in placental and fetal tissues, suggesting a role for leptin in placental and/or fetal growth, or both. In humans, leptin concentrations in adulthood are inversely related to body weight at birth, independent of adult adiposity, and correlate with fasting insulin. Glucocorticoids and insulin regulate leptin secretion. Excessive exposure to glucocorticoids during late fetal development in the rat causes intrauterine growth retardation (IUGR), together with hypertension and hyperinsulinaemia in adulthood. Leptin may have a role in the development of some forms of hypertension. Objective: To determine whether IUGR induced by maternal glucocorticoid treatment during the last third of pregnancy in the rat is associated with modulation of either maternal or fetal leptin concentrations, the placental expression of leptin or the short form of the leptin receptor (ObR-S), or combinations thereof, and to evaluate whether hypertension or hyperinsulinaemia in the earlygrowth-retarded adult progeny of dexamethasone-treated dams is associated with altered leptin concentrations. Design and Methods: Dexamethasone was administered to pregnant rats from day 15 to day 21 of gestation via a chronically implanted subcutaneous osmotic minipump. Protein expression of leptin and ObR-S in the placenta at day 21 of pregnancy was measured by western blotting. Plasma leptin and insulin concentrations were determined by radioimmunoassay and ELISA respectively. Systolic hypertension was measured by tail cuff plethysmography. Results: Dexamethasone administration during the last third of pregnancy decreased placental mass and fetal body weight at day 21 of gestation, caused maternal hyperleptinaemia but fetal hypoleptinaemia, and suppressed placental leptin protein expression whilst up-regulating placental protein expression of ObR-S. The male and female offspring of dexamethasone-treated dams were hypertensive from 12 weeks of age. One-year-old offspring of dexamethasone-treated dams exhibited signi®cant hyperleptinaemia compared with age-matched controls, an effect associated with hyperinsulinaemia in the male, but not female, offspring. Conclusions: The rat model of maternal dexamethasone treatment is established as a paradigm of programmed' hypertension in man. Our data show modi®cation of placental leptin and leptin receptor protein expression by dexamethasone treatment during the last third of pregnancy. We also show that leptin concentrations are suppressed during fetal life but increased in adulthood in this rat model of programmed hypertension. Our data do not necessarily establish a causal relationship between fetal hypoleptinaemia and impaired fetal growth during early life, or between hyperleptinaemia and hypertension in adulthood. Nevertheless, they suggest that hyperleptinaemia may be a component of the cluster of metabolic abnormalities seen in the insulin resistance syndrome in man. They also suggest that excessive...

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Section: Discussionsupporting

confidence: 54%

Maternal glucocorticoid treatment modulates placental leptin and leptin receptor expression and materno-fetal leptin physiology during late pregnancy, and elicits hypertension associated with hyperleptinaemia in the early-growth-retarded adult offspring

Sugden

Langdown²,

Munns³

et al. 2001

European Journal of Endocrinology

120

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“…The plasma levels of leptin are highly correlated with adipose tissue mass and fall in both humans and mice after weight loss (Maffei et al, 1995). Kronfeld-Schor et al (2000) directly demonstrated that leptin secretion rates from mouse adipose tissue in vitro are decreased during early pregnancy and up-regulated during late pregnancy and lactation and these changes in leptin secretion rates in vitro paralleled those of circulating leptin in vivo during pregnancy. On the other hand, the increase in circulating leptin levels during mid to late pregnancy does not consistently correlate with adiposity in rats (Kawai et al, 1997;Amico et al, 1998), mice Tomimatsu et al, 1997), and humans (Butte et al, 1997).…”

Section: Expression Of Leptin Rna In the Adipose Tissue Of Non Pregnamentioning

confidence: 91%

“…One possible explanation for this is that adipose tissue continues to secrete leptin for a brief time after parturition (Kronfeld-Schor et al, 2000).…”

Section: Expression Of Leptin Rna In the Placenta During Pregnancy Inmentioning

confidence: 99%

Leptin Gene Expression in Rabbits During Pregnancy and Fetal Life

Kirat¹,

Hamid²,

Mohamed³

et al. 2015

IJB

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Leptin may act as the critical link between adipose tissue and reproduction. Although considerable progress has been achieved in understanding the reproductive actions of leptin, much work is needed for understanding its physiological role. Till now, no data has been published about the distribution and expression levels of leptin in the rabbit maternal adipose tissue, placenta, and various fetal rabbit tissues during pregnancy and postpartum. Our results indicated that circulating leptin levels in rabbit serum during pregnancy were significantly higher than in postpartum and non pregnant rabbits. Furthermore, leptin showed positive correlations with body weight and estrogen and negative correlation with progesterone in pregnant and postpartum rabbits. RT-PCR verified the presence of RNAs encoding leptin in the rabbit maternal perirenal adipose tissue, placenta, and several fetal tissues; including brain, liver, adipose tissue, and bone. The relative abundance of leptin RNA in rabbit maternal adipose was significantly higher at 20 th day of pregnancy than that of non pregnant rabbits, while it was significantly decreased at 2 nd day after parturition. No significant changes in the placental leptin RNA levels were noticed in pregnant rabbits at 10 th , 20 th , and 30 th day of pregnancy. The relative abundance of fetal leptin transcripts at day 30 th of pregnancy was in the order of liver> bone ≥ adipose tissue > brain. The present study provides new evidence for the distribution and expression levels of leptin in the rabbit maternal and fetal tissues during pregnancy and supports the importance of leptin in reproductive physiology and fetal development.

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“…Decreased leptin mRNA expression in visceral fat at D14 may limit placental soluble Ob-R mediated hyperleptinemia at the initiation of placental soluble Ob-R secretion in accordance with low fetal energy demands during early to middle gestation and the maternal body prepares for the elevated metabolic demands of late pregnancy and lactation. 9,35,36) At D17, leptin mRNA expression in visceral fat from ZnDF pregnant mice significantly decreased to 50% and that of placental soluble Ob-R mRNA and Ob-R protein decreased to 75% and 40% compared with that observed in control mice, respectively. In contrast, the expression of placental soluble Ob-R mRNA and Ob-R protein in ZnSP pregnant mice tended to increase to 120% and 140%, respectively, compared with that observed in control mice.…”

Section: Discussionmentioning

confidence: 95%

“…Tomimatsu et al suggested that plasma leptin concentrations dramatically rise from D10.5, peak during the third trimester of pregnancy, and rapidly decrease to non-pregnant levels during lactation. 9,35,36) These dramatic increases suggest that leptin may be particularly important during stages of fetal growth and development (late pregnancy) but less so during stages of organogenesis (early pregnancy). During pregnancy, leptin may act on the hypothalamus and regulate energy expenditure, neuroendocrine functions, glucose metabolism, and insulin sensitivity in dams.…”

Section: Discussionmentioning

confidence: 99%

Effects of Zinc Deficiency and Supplementation on Leptin and Leptin Receptor Expression in Pregnant Mice

Ueda

Nakai

Konishi

et al. 2014

Biological & Pharmaceutical Bulletin

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Leptin is an adipose-derived hormone that primarily regulates energy balance in response to nutrition. Human placental cells produce leptin, whereas murine placental cells produce soluble leptin receptors (Ob-R). However, the roles of these proteins during pregnancy have not been elucidated completely. As an essential metal, zinc (Zn) is central to insulin biosynthesis and energy metabolism. In the present study, the effects of Zn deficiency and supplementation on maternal plasma leptin and soluble Ob-R regulation in pregnant mice placentas were examined using enzyme-linked immunosorbent assay, reverse transcriptionpolymerase chain reaction, and Western blotting. Nutritional Zn deficiency significantly reduced plasma insulin concentrations and fetal and placental weights in pregnant mice. Plasma leptin concentrations in pregnant mice also increased 20-to 40-fold compared with those in non-pregnant mice. Although dietary Zn deficiency and supplementation did not affect plasma leptin concentrations in non-pregnant mice, Zndeficient pregnant mice had significantly reduced plasma leptin concentrations and adipose leptin mRNA expression. In contrast, Zn-supplemented pregnant mice had increased plasma leptin concentrations without increased adipose leptin mRNA expression. Placental soluble Ob-R mRNA expression also decreased in Zndeficient mice and tended to increase in Zn-supplemented mice. These results indicate that Zn influences plasma leptin concentrations by modulating mRNA expression of soluble Ob-R in the placenta, and leptin in visceral fat during pregnancy. These data suggest that both adipose and placenta-derived leptin system are involved in the regulation of energy metabolism during fetal growth. Key words leptin; leptin receptor; dietary zinc; pregnancy; placentaLeptin is a 16-kDa protein hormone encoded by lep and is mainly produced in adipose tissues. Initial studies indicated that it regulates body weight by suppressing appetite and stimulating energy consumption via the hypothalamic leptin receptor (Ob-R).1,2) In addition to its known role in energy metabolism, pleiotropic effects of leptin have been identified, involving modulation of thermogenesis, homeostasis, hematopoiesis, angiogenesis, neuroendocrine, and immune functions. Moreover, leptin regulates ovarian function, oocyte maturation, and implantation.3,4) Recently, significantly elevated plasma leptin concentrations were found in pregnant women, with considerable leptin secretion from the placenta in comparison with that observed in non-pregnant women. 5)In the second and third trimesters, plasma leptin concentrations further increased in comparison with that observed in the first trimester and returned to normal after expulsion of placenta, suggesting that the placenta is the major source of leptin during pregnancy. 5) Leptin is not produced in mouse placentas, although plasma leptin concentrations are also elevated during pregnancy, and high placental production of soluble Ob-R has been demonstrated in mice. It was reported that secretions ...

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Steroid-Dependent Up-Regulation of Adipose Leptin Secretion In Vitro During Pregnancy in Mice1

Cited by 43 publications

References 47 publications

Maternal glucocorticoid treatment modulates placental leptin and leptin receptor expression and materno-fetal leptin physiology during late pregnancy, and elicits hypertension associated with hyperleptinaemia in the early-growth-retarded adult offspring

Maternal glucocorticoid treatment modulates placental leptin and leptin receptor expression and materno-fetal leptin physiology during late pregnancy, and elicits hypertension associated with hyperleptinaemia in the early-growth-retarded adult offspring

Leptin Gene Expression in Rabbits During Pregnancy and Fetal Life

Effects of Zinc Deficiency and Supplementation on Leptin and Leptin Receptor Expression in Pregnant Mice

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