Gestational Profile of Leptin Messenger Ribonucleic Acid (mRNA) Content in the Placenta and Adipose Tissue in the Rat, and Regulation of the mRNA Levels of the Leptin Receptor Subtypes in the Hypothalamus During Pregnancy and Lactation1

This study examined the pattern of circulating leptin in age-matched sheep during adolescent pregnancy, and its relationship with maternal dietary intake, body composition and tissue expression of the leptin gene. Overfeeding the adolescent pregnant ewe results in rapid maternal growth at the expense of the placenta, leading to growth restriction in the fetus, compared with normal fed controls. Our results demonstrate that, in the adolescent ewe, overfeeding throughout pregnancy was associated with higher maternal leptin concentrations, when compared with moderately fed controls (P<0.05), with no peak in circulating leptin towards the end of pregnancy. There was a close correlation between indices of body composition and circulating leptin levels at day 104 of gestation and at term (P<0.03). Further, when the dietary intake was switched from moderate to high, or high to moderate, at day 50 of gestation, circulating leptin levels changed rapidly, in parallel with the changes in dietary intake. Leptin mRNA levels and leptin protein in perirenal adipose tissue samples, taken at day 128 of gestation, were higher in overfed dams (P<0.04), suggesting that adipose tissue was the source of the increase in circulating leptin in the overnourished ewes. Leptin protein was also detected in placenta but leptin gene expression was negligible. However, leptin receptor gene expression was detected in the ovine placenta, suggesting that the placenta is a target organ for leptin. A negative association existed between maternal circulating leptin and fetal birth weight, placental/cotyledon weight and cotyledon number. In conclusion, in this particular ovine model, hyperleptinaemia was not observed during late pregnancy. Instead, circulating leptin concentrations reflected increased levels of leptin secretion by adipose tissue primarily as a result of the increase in body fat deposition, due to overfeeding. However, there appears to be a direct effect of overfeeding, particularly in the short term. In the nutritional switch-over study, circulating leptin concentrations changed within 48 h of the change in dietary intake. The presence of leptin protein and leptin receptor gene expression in the placenta suggests that leptin could be involved in nutrient partitioning during placental and/or fetal development.

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Growth Hormone (GH) Substitution in GH-Deficient Patients Inhibits 11β-Hydroxysteroid Dehydrogenase Type 1 Messenger Ribonucleic Acid Expression in Adipose Tissue

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2005-1694 ◽

2006 ◽

Vol 91 (3) ◽

pp. 1093-1098 ◽

Cited By ~ 38

Author(s):

Søren Kildeberg Paulsen ◽

Steen Bønløkke Pedersen ◽

Jens Otto Lunde Jørgensen ◽

Sanne Fisker ◽

Jens Sandahl Christiansen ◽

...

Keyword(s):

Growth Hormone ◽

Adipose Tissue ◽

Ribonucleic Acid ◽

Hydroxysteroid Dehydrogenase ◽

Messenger Ribonucleic Acid

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Suppression of Leptin Receptor Messenger Ribonucleic Acid and Leptin Responsiveness in the Ventromedial Nucleus of the Hypothalamus during Pregnancy in the Rat

Endocrinology ◽

10.1210/en.2005-0194 ◽

2005 ◽

Vol 146 (9) ◽

pp. 3868-3874 ◽

Cited By ~ 81

Author(s):

S. R. Ladyman ◽

D. R. Grattan

Keyword(s):

Choroid Plexus ◽

Arcuate Nucleus ◽

Leptin Receptor ◽

Leptin Resistance ◽

Ventromedial Nucleus ◽

Mrna Levels ◽

Pregnant Rats ◽

Messenger Ribonucleic Acid ◽

Leptin Receptors ◽

Receptor Isoforms

Abstract Pregnancy in the rat is a state of leptin resistance associated with impaired leptin signal transduction in the hypothalamus. The aim of this study was to determine whether this leptin-resistant state is mediated by a change in the level of leptin receptors in the hypothalamus. Real-time RT-PCR was used to determine levels of mRNA for the various leptin receptor isoforms in a number of microdissected hypothalamic nuclei and the choroid plexus. To investigate the functional activation of the leptin receptor, immunohistochemistry for phosphorylated signal transducer and activator of transcription 3 (pSTAT3) was examined in the arcuate nucleus and the ventromedial nucleus of the hypothalamus (VMH) of fasted diestrous and d-14 pregnant rats after an intracerebroventricular (i.c.v.) injection of either leptin (4 μg) or vehicle. A significant reduction of Ob-Rb mRNA levels was observed in the VMH during pregnancy compared with the nonpregnant controls. Furthermore, in pregnant rats the number of cells positive for leptin-induced pSTAT3 in the VMH was greatly reduced during pregnancy compared with nonpregnant rats. There were no differences in the level of Ob-Rb mRNA or in the number of leptin-induced pSTAT3-positive cells in the arcuate nucleus of nonpregnant and pregnant rats. These data implicate the VMH as a key hypothalamic site involved in pregnancy-induced leptin resistance. There were also reduced levels of mRNA for Ob-Ra, a proposed leptin transporter molecule, in the choroid plexus on d 7 and 21 of pregnancy. Hence, diminished transport of leptin into the brain may also contribute to pregnancy-induced leptin resistance.

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Maternal undernutrition programs the apelinergic system of adipose tissue in adult male rat offspring

Journal of Developmental Origins of Health and Disease ◽

10.1017/s2040174416000702 ◽

2017 ◽

Vol 8 (1) ◽

pp. 3-7 ◽

Cited By ~ 5

Author(s):

S. Lecoutre ◽

L. Marousez ◽

A. Drougard ◽

C. Knauf ◽

C. Guinez ◽

...

Keyword(s):

Adipose Tissue ◽

Adult Male ◽

Messenger Rna ◽

Leptin Receptor ◽

Female Rats ◽

Male Rat ◽

Mrna Levels ◽

Maternal Undernutrition ◽

Rat Offspring ◽

Adult Male Rat

Based on the Developmental Origin of Health and Disease concept, maternal undernutrition has been shown to sensitize adult offspring to metabolic pathologies such as obesity. Using a model of maternal 70% food restriction in pregnant female rats throughout gestation (called FR30), we previously reported that obesity-prone adult male rat offspring displayed hyperleptinemia with modifications in leptin and leptin receptor messenger RNA (mRNA) levels in white adipose tissue (WAT). Apelin is a member of the adipokine family that regulates various aspects of energy metabolism and WAT functionality. We investigated whether apelin and its receptor APJ could be a target of maternal undernutrition. Adult male rat offspring from FR30 dams showed increased plasma apelin levels and apelin gene expression in WAT. Post-weaning high-fat diet led to marked increase in APJ mRNA and protein levels in offspring’s WAT. We demonstrate that maternal undernutrition and post-weaning diet have long-term consequences on the apelinergic system of adult male rat offspring.

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Characterization of β-adrenergic receptors in bovine intramuscular and subcutaneous adipose tissue: comparison of lubabegron fumarate with β-adrenergic receptor agonists and antagonists

Journal of Animal Science ◽

10.1093/jas/skab116 ◽

2021 ◽

Vol 99 (8) ◽

Author(s):

Jinhee H Hwang ◽

Michael E Spurlock ◽

John C Kube ◽

Xiang Z Li ◽

Stephen B Smith

Keyword(s):

Adipose Tissue ◽

Adrenergic Receptor ◽

Quantitative Polymerase Chain Reaction ◽

Animal Health ◽

Chinese Hamster ◽

Ovary Cell ◽

Receptor Subtype ◽

Receptor Subtypes ◽

Mrna Levels ◽

Adipose Tissues

Abstract Chinese hamster ovary cell constructs expressing either the β 1-, β 2- or β 3-adrenergic receptor (AR) were used to determine whether a novel β-AR modulator, lubabegron fumarate (LUB; Experior, Elanco Animal Health) might exert greater potency for a specific β-AR subtype. EC50 values calculated based on cAMP accumulation in dose response curves indicate that LUB is highly selective for the β 3-AR subtype, with an EC50 of 6 × 10–9 M, with no detectible agonistic activity at the β 2-AR. We hypothesized that the accumulation of lipolytic markers would reflect the agonist activity at each of the β-receptor subtypes of the specific ligand; additionally, there would be differences in receptor subtype expression in subcutaneous (s.c.) and intrmuscular (i.m.) adipose tissues. Total RNA was extracted from adipose tissue samples and relative mRNA levels for β 1-, β2-, and β 3-AR were measured using real-time quantitative polymerase chain reaction. Fresh s.c. and i.m. adipose tissue explants were incubated with isoproterenol hydrochloride (ISO; β-AR pan-agonist), dobutamine hydrochloride (DOB; specific β 1-AA), salbutamol sulfate (SAL; specific β 2-AA), ractopamine hydrochloride (RAC), zilpaterol hydrochloride (ZIL), BRL-37344 (specific β 3-agonist), or LUB for 30 min following preincubation with theophylline (inhibitor of phosphodiesterase). Relative mRNA amounts for β 1-, β 2-, and β 3-AR were greater (P < 0.05) in s.c. than in i.m. adipose tissue. The most abundant β-AR mRNA in both adipose tissues was the β 2-AR (P < 0.05), with the β 1- and β 3-AR subtypes being minimally expressed in i.m. adipose tissue. ISO, RH, and ZH stimulated the release of glycerol and nonesterified fatty acid (NEFA) from s.c. adipose tissue, but these β-AR ligands did not alter concentrations of these lipolytic markers in i.m. adipose tissue. LUB did not affect glycerol or NEFA concentrations in s.c. or i.m. adipose tissue, but attenuated (P < 0.05) the accumulation of cAMP mediated by the β 1- and β 2-AR ligands DOB and SAL in s.c. adipose tissue. Collectively, these data indicate that bovine i.m. adipose tissue is less responsive than s.c. adipose tissue to β-adrenergic ligands, especially those that are agonists at the β 1- and β3-receptor subtypes. The minimal mRNA expression of the β 1- and β 3 subtypes in i.m. adipose tissue likely limits the response potential to agonists for these β-AR subtypes.

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