Ontogeny and insulin regulation of fetal ovine white  adipose tissue leptin expression

Devaskar, Sherin U.; Anthony, R. V.; Hay, William W.

doi:10.1152/ajpregu.2002.282.2.r431

Cited by 51 publications

(43 citation statements)

References 44 publications

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“…Our current Dex-associated changes are consistent with that reported previously in the intrauterine growth-restricted (IUGR) progeny (8,39). In the IUGR progeny, calorie restriction begins in utero, resulting in persistence of growth failure into adulthood (27,49).…”

Section: Day Oldsupporting

confidence: 90%

“…In the IUGR progeny, calorie restriction begins in utero, resulting in persistence of growth failure into adulthood (27,49). The IUGR offspring has low insulin (39) and leptin concentrations in utero (8), while the impact on endogenous corticosterone concentrations has been controversial, with some studies demonstrating no effect (4, 36) and others showing an increase that may cause the programming effects observed in the adult (30,33). In conjunction with these hormonal effects, a sustained postnatal increase in hypothalamic neuropeptide Y concentrations is observed in the IUGR (39) and in the maternally deprived offspring (24).…”

Section: Day Oldmentioning

confidence: 99%

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Postnatal glucocorticoid exposure alters the adult phenotype

He¹,

Varma²,

Weissfeld³

et al. 2004

American Journal of Physiology-Regulatory, Integrative and Comp

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He, Jing, Amit Varma, Lisa A. Weissfeld, and Sherin U. Devaskar. Postnatal glucocorticoid exposure alters the adult phenotype. Am J Physiol Regul Integr Comp Physiol 287: R198 -R208, 2004. First published March 4, 2004 10.1152/ajpregu.00349.2003We examined the effect of six doses of dexamethasone (Dex) administered daily (2-7 days of age) to postnatal rats on body weight gain, food and water intake, peripheral hormonal/metabolic milieu, and hypothalamic neuropeptides that regulate food intake. We observed a Dex-induced acute (3 days of age) suppression of endogenous corticosterone and an increase in circulating leptin concentrations that were associated with a decrease in body weight in males and females. Followup during the suckling, postsuckling, and adult stages (7-120 days of age) revealed hypoleptinemia in males and females, and hypoinsulinemia, a relative increase in the glucose-to-insulin ratio, and a larger increase in skeletal muscle glucose transporter (GLUT 4) concentrations predominantly in the males, reflective of a catabolic state associated with a persistent decrease in body weight gain. The increase in the glucose-to-insulin ratio and hyperglycemia was associated with an increase in water intake. In addition, the changes in the hormonal/metabolic milieu were associated with an increase in hypothalamic neuropeptide Y content in males and females during the suckling phase, which persisted only in the 120-day-old female with a transient postnatal decline in ␣-melanocyte-stimulating hormone and corticotropin-releasing factor. This increase in neuropeptide Y (NPY) during the suckling phase in males and females was associated with a subsequent increase in adult food intake that outweighed the demands of body weight gain. In contrast to the adult hypothalamic findings, cerebral ventricular dilatation was more prominent in adult males. We conclude that postnatal Dex treatment causes permanent sex-specific changes in the adult phenotype, setting the stage for future development of diabetes (increased glucose:insulin ratio), obesity (increased NPY and food intake), and neurological impairment (loss of cerebral volume). development; food intake; neuropeptide Y; glucose transporters POSTNATAL GLUCOCORTICOID THERAPY constituted a standard intervention to combat chronic lung disease in the newborn premature infant (18,40). Recent reports of adverse outcomes such as cerebral palsy have cautioned the clinicians into judicious use of this drug (2, 17, 50). However, there still continue to be certain infants with chronic lung changes who are resilient to conventional modes of therapy warranting the use of postnatal glucocorticoids as a life-saving intervention (19,42). Furthermore, despite the absence of well-controlled trials, glucocorticoids are still used in term infants for differing indications other than prevention of chronic lung disease. While the adverse effects of antenatal glucocorticoid therapy have been examined and long-term changes reported in animals (13,20,33,37,38), limited studies exist in resp...

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Section: Day Oldsupporting

confidence: 90%

Section: Day Oldmentioning

confidence: 99%

Postnatal glucocorticoid exposure alters the adult phenotype

He¹,

Varma²,

Weissfeld³

et al. 2004

American Journal of Physiology-Regulatory, Integrative and Comp

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“…In fetal sheep, plasma leptin concentrations increased transiently 24-48 h after the onset of fetal cortisol infusion but were normal on the fifth day of infusion at the time when perirenal adipose tissue was collected in the present study (Forhead et al 2002). In previous studies of fetal sheep, both increases and decreases in leptin expression have been observed in perirenal adipose tissue over the same period of late gestation examined in the present study (Yuen et al 1999, Devasker et al 2002. This may be explained, in part, by breed differences in leptin expression (Dandrea 2001) but may also reflect differences in nutritional intake by the ewes between early to mid gestation, when a reduction in maternal food intake results in increased leptin mRNA in fetal adipose tissue as measured near to term .…”

Section: Discussionsupporting

confidence: 53%

Influence of cortisol on adipose tissue development in the fetal sheep during late gestation

Mostyn¹,

Pearce²,

Budge³

et al. 2003

Journal of Endocrinology

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The present study examined the extent to which the late gestation rise in fetal plasma cortisol influenced adipose tissue development in the fetus. The effect of cortisol on the abundance of adipose tissue mitochondrial proteins on both the inner (i.e. uncoupling protein (UCP)1) and outer (i.e. voltage-dependent anion channel (VDAC)) mitochondrial membrane, together with the long and short forms of the prolactin receptor (PRLR) protein and leptin mRNA was determined. Perirenal adipose tissue was sampled from ovine fetuses to which (i) cortisol (2-3 mg/ day for 5 days) or saline was infused up to 127-130 days of gestation, and (ii) adrenalectomised and intact controls at between 142 and 145 days of gestation (term=148 days). UCP1 protein abundance was significantly lower in adrenalectomised fetuses compared with age-matched controls, and UCP1 was increased by cortisol infusion and with gestational age. Adrenalectomy reduced the concentration of the long form of PRLR, although this effect was only significant for the highest molecular weight isoform. In contrast, neither the short form of PRLR, VDAC protein abundance or leptin mRNA expression was significantly affected by gestational age or cortisol status. Fetal plasma triiodothyronine concentrations were increased by cortisol and with gestational age, an affect abolished by adrenalectomy. When all treatment groups were combined, both plasma cortisol and triiodothyronine concentrations were positively correlated with UCP1 protein abundance. In conclusion, an intact adrenal is necessary for the late gestation rise in UCP1 protein abundance but cortisol does not appear to have a major stimulatory role in promoting leptin expression in fetal adipose tissue. It remains to be established whether effects on UCP1 protein are directly regulated by cortisol alone or mediated by other anabolic fetal hormones such as triiodothyronine.

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“…This is an example of a sexspecific "neuropeptide imprinting" effect secondary to postnatal leptin exposure constituting "hormonal imprinting." The significance of our observations relates to the offspring of a diabetic mother exhibiting high levels of circulating leptin at birth (17,32) and low concentrations of brain NPY just before birth (49). The level of hyperleptinemia at birth may result in either leptin sensitivity or resistance, thereby contributing toward heterogeneity in clinical presentation by predetermining the adult phenotype.…”

Section: Discussionmentioning

confidence: 87%

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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Ontogeny and insulin regulation of fetal ovine white adipose tissue leptin expression

Cited by 51 publications

References 44 publications

Postnatal glucocorticoid exposure alters the adult phenotype

Postnatal glucocorticoid exposure alters the adult phenotype

Influence of cortisol on adipose tissue development in the fetal sheep during late gestation

Postnatal intracerebroventricular exposure to leptin causes an altered adult female phenotype

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