scholarly journals Fetal endocrinology and development--manipulation and adaptation to long-term nutritional and environmental challenges

Reproduction ◽  
2001 ◽  
pp. 853-862 ◽  
Author(s):  
ME Symonds ◽  
H Budge ◽  
T Stephenson ◽  
IC McMillen
Keyword(s):  
Adipose Tissue ◽  
Maternal Nutrition ◽  
Uncoupling Protein ◽  
Prolactin Receptor ◽  
Endocrine System ◽  
Adult Obesity ◽  
Maternal Undernutrition ◽  
Increased Risk ◽  
Long Form

This article reviews the fetal endocrine system in sheep, a species that has a long gestation and primarily produces a singleton fetus. Attention is focused on information that is applicable to humans. The endocrinology of metabolic homeostasis in sheep fetuses is well adapted to respond to a range of metabolic challenges, including placental restriction and maternal undernutrition. A small placenta results in hypoxaemia, hypoglycaemia, reduced abundance of anabolic hormones, and fetal growth restriction. Fetuses with restricted growth are characterized by tissue-specific reductions in hormone receptor mRNA, for example mRNA for the long form of prolactin receptor is reduced in adipose tissue. In contrast, the adipose tissue of fetuses with accelerated growth, stimulated by increasing maternal nutrition in the second half of gestation, has more protein for the long form of the prolactin receptor and more uncoupling protein 1, by which large amounts of heat are generated at birth. Maternal undernutrition in early gestation, coinciding with the period of rapid placental growth, initially restricts placental growth, but when mothers are fed to requirements, a longer fetus results with a disproportionately large placenta. This nutritional manipulation replicates, in part, epidemiological findings from the Dutch famine of 1944-1945, for which the offspring are at increased risk of adult obesity.

Fetal and neonatal adipose maturation: a primary site of cytokine and cytokine-receptor action

2001 ◽  
Vol 29 (2) ◽  
pp. 80-85 ◽  
Author(s):  
T. Stephenson ◽  
H. Budge ◽  
A. Mostyn ◽  
S. Pearce ◽  
R. Webb ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Maternal Nutrition ◽  
Short Form ◽  
Uncoupling Protein ◽  
Prolactin Receptor ◽  
Late Gestation ◽  
Metabolic Adaptation ◽  
Postnatal Life ◽  
Brown Adipose

During late gestation, the maturation of fetal adipose tissue is geared towards the synthesis of high levels of uncoupling protein 1 (UCP1), which is unique to brown adipose tissue. At birth, rapid activation of UCP1 ensures a large increase in heat production. These adaptations are nutritionally sensitive, and may be mediated in part by rapid changes in prolactin and leptin secretion after birth. Restriction of maternal nutrition reduces adipose tissue deposition, with no effect on UCP1. Increased maternal food intake results in increases in levels of UCP1 and the short form of the prolactin receptor, but in a decrease in adipose tissue content per kg of fetus. The ontogeny of the long and short forms of the prolactin receptor follows that of UCP1, to peak at birth. Then, during postnatal life, UCP1 disappears in parallel with the loss of prolactin receptors. Treatment of neonatal lambs with prolactin increases body temperature and the thermogenic potential of brown adipose tissue. In contrast, acute leptin treatment results in maintenance of colonic temperature, but chronic leptin treatment accelerates UCP1 loss. Increasing our understanding of the interaction between prolactin and leptin during perinatal development may enable the establishment of strategies aimed at maximizing adipose tissue development in order to promote metabolic adaptation to the extra-uterine environment.

Role of maternal nutrition in programming adiposity in the offspring: potential implications of glucocorticoids

2013 ◽  
Vol 14 (1) ◽  
Author(s):  
Christophe Breton
Keyword(s):  
Adipose Tissue ◽  
Birth Weight ◽  
Energy Homeostasis ◽  
Maternal Obesity ◽  
Maternal Nutrition ◽  
The Body ◽  
High Birth Weight ◽  
Storage Unit ◽  
Maternal Undernutrition ◽  
Increased Risk

AbstractThe epidemiological studies initially indicated that maternal undernutrition leading to a low birth weight may predispose to the long-lasting energy balance disorders. A high birth weight due to maternal obesity or diabetes, inappropriate early postnatal nutrition, and rapid catch-up growth, may also sensitize to an increased risk of obesity. As stated by the developmental origin of health and disease concept, the perinatal perturbation of the fetus/neonate nutrient supply might be a crucial determinant of the individual programming of the body weight set point. The adipose tissue is considered as the main fuel storage unit involved in the maintenance of the energy homeostasis. Several models have demonstrated that this tissue is a prime target of the developmental programming in a gender- and depot-specific manner. In the rodents, the perinatal period of life corresponds largely to the period of adipogenesis. In contrast, this phenomenon essentially takes place before birth in bigger mammals. Despite these different developmental time windows, the altricial and precocial species share several common offspring programming mechanisms. Thus, the adipose tissue of the offspring from malnourished dams exhibited impaired glucose uptake and leptin/insulin resistance with increased proinflammatory markers. It also displayed a modified sympathetic activity, circadian rhythm, fatty acid composition, and thermogenesis. This might lead to the reprogrammed metabolism and distribution of the adipose tissue with enhanced adipogenesis and fat accumulation predisposing to adiposity. The inappropriate glucocorticoid (GC) levels and modified tissue sensitivity might be key actors of perinatal programming and long-lasting altered adipose tissue activity in the offspring. Following maternal malnutrition, the epigenetic mechanisms might also be responsible for the adipose tissue programming.

scholarly journals Timing of nutrient restriction and programming of fetal adipose tissue development

2004 ◽  
Vol 63 (3) ◽  
pp. 397-403 ◽  
Author(s):  
Michael E. Symonds ◽  
Sarah Pearce ◽  
Jayson Bispham ◽  
David S. Gardner ◽  
Terence Stephenson
Keyword(s):  
Adipose Tissue ◽  
Uncoupling Protein ◽  
Tissue Growth ◽  
Fat Deposition ◽  
Late Gestation ◽  
Nutrient Restriction ◽  
Adult Obesity ◽  
Uncoupling Protein 1 ◽  
Voltage Dependent Anion Channel ◽  
Brown Adipose

It is apparent from epidemiological studies that the timing of maternal nutrient restriction has a major influence on outcome in terms of predisposing the resulting offspring to adult obesity. The present review will consider the extent to which maternal age, parity and nutritional restriction at defined stages of gestation can have important effects on fat deposition and endocrine sensitivity of adipose tissue in the offspring. For example, in 1-year-old sheep the offspring of juvenile mothers have substantially reduced fat deposition compared with those born to adult mothers. Offspring of primiparous adult mothers, however, show increased adiposity compared with those born to multiparous mothers. These offspring of multiparous ewes show retained abundance of the brown adipose tissue-specific uncoupling protein 1 at 1 month of age. A stimulated rate of metabolism in brown fat of these offspring may act to reduce adipose tissue deposition in later life. In terms of defined windows of development that can programme adipose tissue growth, maternal nutrient restriction targetted over the period of maximal placental growth results in increased adiposity at term in conjunction with enhanced abundance of mRNA for the insulin-like growth factor-I and -II receptors. In contrast, nutrient restriction in late gestation, coincident with the period of maximal fetal growth, has no major effect on adiposity but results in greater abundance of specific mitochondrial proteins, i.e. voltage-dependent anion channel and/or uncoupling protein 2. These adaptations may increase the predisposal of these offspring to adult obesity. Increasing maternal nutrition in late gestation, however, can result in proportionately less fetal adipose tissue deposition in conjunction with enhanced abundance of uncoupling protein 1.

Glucocorticoids and insulin: complex interaction on brown adipose tissue

1995 ◽  
Vol 268 (5) ◽  
pp. R1209-R1216 ◽  
Author(s):  
A. M. Strack ◽  
C. J. Horsley ◽  
R. J. Sebastian ◽  
S. F. Akana ◽  
M. F. Dallman
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
Diabetic Rats ◽  
Insulin Effect ◽  
Caloric Efficiency ◽  
Brown Adipose ◽  
System Input ◽  
Streptozotocin Induced Diabetes

Glucocorticoids and insulin effect long-term reciprocal changes in food intake and body weight. We tested the interactions of corticosterone and insulin on caloric efficiency, white adipose tissue (WAT) stores, and brown adipose tissue (BAT). Two experiments were performed: 1) adrenalectomized rats were treated with corticosterone with or without streptozotocin-induced diabetes and 2) adrenalectomized, corticosterone-treated, diabetic rats were treated with insulin. By 4-5 days later, > or = 50% of the variance in caloric efficiency, plasma triglycerides, and WAT stores was explained by regression of these variables on corticosterone (catabolic) and insulin (anabolic). When the ratio of the hormones was normal, but concentrations high, overall gain of energy stores decreased and energy was redistributed to fat. Both hormones were anabolic on BAT lipid storage; the hormones played a complex role in the regulation of uncoupling protein (UCP) in BAT. Although corticosterone inhibited and insulin stimulated UCP, these effects were only evident in diabetics and with normoglycemia, respectively. For BAT variables, < or = 50% of the variance was explained by regression on corticosterone and insulin, suggesting that the effects of these hormones are mediated through an intermediate such as sympathetic nervous system input to BAT.

Long-term hypoxia modulates expression of key genes regulating adipose function in the late-gestation ovine fetus

2008 ◽  
Vol 294 (4) ◽  
pp. R1312-R1318 ◽  
Author(s):  
Dean A. Myers ◽  
Krista Hanson ◽  
Malgorzata Mlynarczyk ◽  
Kanchan M. Kaushal ◽  
Charles A. Ducsay
Keyword(s):  
Adipose Tissue ◽  
Uncoupling Protein ◽  
Late Gestation ◽  
Peroxisome Proliferator ◽  
Local Synthesis ◽  
Major Function ◽  
Ovine Fetus ◽  
Key Genes

A major function of abdominal adipose in the newborn is nonshivering thermogenesis. Uncoupling protein (UCP) UCP1 and UCP2 play major roles in thermogenesis. The present study tested the hypothesis that long-term hypoxia (LTH) modulates expression of UCP1 and UCP2, and key genes regulating expression of these genes in the late-gestation ovine fetus. Ewes were maintained at high altitude (3,820 m) from 30 to 138 days gestation (dG); perirenal adipose tissue was collected from LTH and age-matched, normoxic control fetuses at 139–141 dG. Quantitative real-time PCR was used to analyze mRNA for UCP1, UCP2, 11β hydroxysteroid dehydrogenase type 1 (HSD11B1) and 2 (HSD11B2), glucocorticoid receptor (GR), β3 adrenergic receptor (β3AR), deiodinase type 1 (DIO1) and DIO2, peroxisome proliferator activated receptor (PPAR) α and γ and PPARγ coactivator 1 (PGC1α). Concentrations of mRNA for UCP1, HSD11B1, PPARγ, PGC1, DIO1, and DIO2 were significantly higher in perirenal adipose of LTH compared with control fetuses, while mRNA for HSD11B2, GR, or PPARα in perirenal adipose did not differ between control and LTH fetuses. The increased expression of UCP1 is likely an adaptive response to LTH, assuring adequate thermogenesis in the event of birth under oxygen-limiting conditions. Because both glucocorticoids and thyroid hormone regulate UCP1 expression, the increase in HSD11B1, DIO1, and DIO2 implicate increased adipose capacity for local synthesis of these hormones. PPARγ and its coactivator may provide an underlying mechanism via which LTH alters development of the fetal adipocyte. These findings have important implications regarding fetal/neonatal adipose tissue function in response to LTH.

Role of T3 in thermogenic and trophic responses of brown adipose tissue to cold

1989 ◽  
Vol 257 (1) ◽  
pp. E81-E87 ◽  
Author(s):  
I. R. Park ◽  
D. B. Mount ◽  
J. Himms-Hagen
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
Optimal Growth ◽  
Endogenous Production ◽  
Brown Adipose ◽  
Trophic Responses ◽  
Optimal Growth Rate

Cold-induced growth of brown adipose tissue (BAT) was studied in thyroidectomized rats that received low doses of either thyroxine (T4) or 3,5,3'-triidothyronine (T3). The objective was to find out whether the cold-induced increase in activity of T4 5'-deiodinase, and thus increased endogenous T3 generation in BAT itself, was necessary for growth of BAT or whether T3 from the blood could serve as effectively as T3 produced endogenously. The acute thermogenic response of BAT to cold (15 h at 4 degrees C), as measured by the increase in mitochondrial GDP binding, was abolished by thyroidectomy, as seen previously, and restored by T3 as well as by T4 treatment. The long-term trophic response to cold (20–25 days at 4 degrees C), as indicated by increases in protein and DNA and in mitochondrial concentrations of GDP-binding sites and uncoupling protein, occurred whether T3 or T4 was administered to these thyroidectomized rats. We conclude that endogenous T3 production in BAT does not direct and is not essential for the long-term trophic response of this tissue to cold. We are not able to exclude, on the basis of the present results, that an optimal growth rate during the initial phase of the trophic response may require enhanced endogenous production of T3 in BAT. The cold-induced increase in T4 5'-deiodinase activity, presumably mediated by an action of norepinephrine, does not require the presence of either T3 or T4, as seen previously by others.

scholarly journals Brown fat thermogenesis in cold-acclimated rats is not abolished by the suppression of thyroid function

2002 ◽  
Vol 283 (3) ◽  
pp. E496-E502 ◽  
Author(s):  
Angel A. Zaninovich ◽  
Marcela Raíces ◽  
Inés Rebagliati ◽  
Conrado Ricci ◽  
Karl Hagmüller
Keyword(s):  
Adipose Tissue ◽  
Cold Exposure ◽  
Cold Adaptation ◽  
Uncoupling Protein ◽  
Mitochondrial Proteins ◽  
Normal Body Temperature ◽  
Brown Adipose ◽  
Normal Controls ◽  
Thermogenic Capacity

The effects of long-term cold exposure on brown adipose tissue (BAT) thermogenesis in hypothyroid rats have been examined. Thyroid ablation was performed in normal rats after 2 mo of exposure to 4°C, when BAT hypertrophy and thermogenic activity were maximal. After ablation, hypothyroid and normal controls remained in the cold for 2 additional months. At the end of the 4-mo cold exposure, all untreated hypothyroid rats were alive, had normal body temperature, and had gained an average 12.8% more weight than normal controls. Long-term cold exposure of hypothyroid rats markedly increased BAT weight, mitochondrial proteins, uncoupling protein (UCP)-1, mRNA for UCP-1, and oxygen consumption to levels similar to those seen in cold-exposed normal rats. The results indicate that thyroid hormones are required for increased thermogenic capacity to occur as an adaptation to long-term cold exposure. However, cold adaptation can be maintained in the absence of thyroid hormone.

scholarly journals Endocrine and nutritional regulation of fetal adipose tissue development

2003 ◽  
Vol 179 (3) ◽  
pp. 293-299 ◽  
Author(s):  
ME Symonds ◽  
A Mostyn ◽  
S Pearce ◽  
H Budge ◽  
T Stephenson
Keyword(s):  
Adipose Tissue ◽  
Maternal Nutrition ◽  
Uncoupling Protein ◽  
Post Partum ◽  
Critical Role ◽  
Plasma Concentrations ◽  
Later Life ◽  
Postnatal Period ◽  
Late Gestation ◽  
Nutritional Regulation

In the fetus, adipose tIssue comprises both brown and white adipocytes for which brown fat is characterised as possessing the unique uncoupling protein (UCP)1. The dual characteristics of fetal fat reflect its critical role at birth in providing lipid that is mobilised rapidly following activation of UCP1 upon cold exposure to the extra-uterine environment. A key stage in the maturation of fetal fat is the gradual rise in the abundance of UCP1. For species with a mature hypothalamic-pituitary axis at birth there is a gradual increase in the amount and activity of UCP1 during late gestation, in conjunction with an increase in the plasma concentrations of catecholamines, thyroid hormones, cortisol, leptin and prolactin. These may act individually, or in combination, to promote UCP1 expression and, following the post-partum surge in each hormone, UCP1 abundance attains maximal amounts.Adipose tIssue grows in the fetus at a much lower rate than in the postnatal period. However, its growth is under marked nutritional constraints and, in contrast to many other fetal organs that are unaffected by nutritional manipulation, fat mass can be significantly altered by changes in maternal and, therefore, fetal nutrition. Fat deposition in the fetus is enhanced during late gestation following a previous period of nutrient restriction up to mid gestation. This is accompanied by increased mRNA abundance for the receptors of IGF-I and IGF-II. In contrast, increasing maternal nutrition in late gestation results in less adipose tIssue deposition but enhanced UCP1 abundance. The pronounced nutritional sensitivity of fetal adipose tIssue to both increased and decreased maternal nutrition may explain why the consequences of an adverse nutritional environment persist into later life.

scholarly journals Undernutrition and stage of gestation influence fetal adipose tissue gene expression

2015 ◽  
Vol 54 (3) ◽  
pp. 263-275 ◽  
Author(s):  
Jacqueline M Wallace ◽  
John S Milne ◽  
Raymond P Aitken ◽  
Dale A Redmer ◽  
Lawrence P Reynolds ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Fatty Acid Synthase ◽  
Uncoupling Protein ◽  
Tissue Development ◽  
Maternal Undernutrition ◽  
Pat Gene ◽  
Adipose Tissue Development ◽  
And Function ◽  
The Impact

Low birthweight is a risk factor for neonatal mortality and adverse metabolic health, both of which are associated with inadequate prenatal adipose tissue development. In the present study, we investigated the impact of maternal undernutrition on the expression of genes that regulate fetal perirenal adipose tissue (PAT) development and function at gestation days 89 and 130 (term=145 days). Singleton fetuses were taken from adolescent ewes that were either fed control (C) intake to maintain adiposity throughout pregnancy or were undernourished (UN) to maintain conception weight but deplete maternal reserves (n=7/group). Fetal weight was independent of maternal intake at day 89, but by day 130, fetuses from UN dams were 17% lighter and had lower PAT mass that contained fewer unilocular adipocytes. Relative PAT expression ofIGF1,IGF2,IGF2Rand peroxisome proliferator-activated receptor gamma (PPARG) mRNA was lower in UN than in controls, predominantly at day 89. Independent of maternal nutrition, PAT gene expression ofPPARG, glycerol-3-phosphate dehydrogenase, hormone sensitive lipase, leptin, uncoupling protein 1 and prolactin receptor increased, whereasIGF1,IGF2,IGF1RandIGF2Rdecreased between days 89 and 130. Fatty acid synthase and lipoprotein lipase (LPL) mRNAs were not influenced by nutrition or stage of pregnancy. Females had greaterLPLand leptin mRNA than males, andLPL, leptin andPPARGmRNAs were decreased in UN at day 89 in females only. PAT gene expression correlations with PAT mass were stronger at day 89 than they were at day 130. These data suggest that the key genes that regulate adipose tissue development and function are active beginning in mid-gestation, at which point they are sensitive to maternal undernutrition: this leads to reduced fetal adiposity by late pregnancy.

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