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.

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.

scholarly journals Prenatal programming of postnatal obesity: fetal nutrition and the regulation of leptin synthesis and secretion before birth

2004 ◽  
Vol 63 (3) ◽  
pp. 405-412 ◽  
Author(s):  
I. C. McMillen ◽  
B. S. Muhlhausler ◽  
J. A. Duffield ◽  
B. S. J. Yuen
Keyword(s):  
Adipose Tissue ◽  
Fat Mass ◽  
Maternal Nutrition ◽  
Adult Life ◽  
Later Life ◽  
Late Gestation ◽  
Relative Mass ◽  
Moderate Increase ◽  
Fetal Life ◽  
Fat Depots

Exposure to either an increased or decreased level of intrauterine nutrition can result in an increase in adiposity and in circulating leptin concentrations in later life. In animals such as the sheep and pig in which fat is deposited before birth, leptin is synthesised in fetal adipose tissue and is present in the fetal circulation throughout late gestation. In the sheep a moderate increase or decrease in the level of maternal nutrition does not alter fetal plasma leptin concentrations, but there is evidence that chronic fetal hyperglycaemia and hyperinsulinaemia increase fetal fat mass and leptin synthesis within fetal fat depots. Importantly, there is a positive relationship between the relative mass of the ‘unilocular’ component of fetal perirenal and interscapular adipose tissue and circulating fetal leptin concentrations in the sheep. Thus, as in the neonate and adult, circulating leptin concentrations may be a signal of fat mass in fetal life. There is also evidence that leptin can act to regulate the lipid storage, leptin synthetic capacity and potential thermogenic functions of fat before birth. Thus, leptin may act as a signal of energy supply and have a ‘lipostatic’ role before birth. Future studies are clearly required to determine whether the intrauterine and early postnatal nutrient environment programme the endocrine feedback loop between adipose tissue and the central and peripheral neuroendocrine systems that regulate energy balance, resulting in an enhanced risk of obesity in adult life.

46 Inhibition of Lipolysis with Acipimox Targets Post-burn White Adipose Browning by Altering Macrophage Polarity

2020 ◽  
Vol 41 (Supplement_1) ◽  
pp. S30-S31
Author(s):  
Dalia Barayan ◽  
Roohi Vinaik ◽  
Marc G Jeschke
Keyword(s):  
Adipose Tissue ◽  
Uncoupling Protein ◽  
Polarization State ◽  
Critical Role ◽  
Metabolic Effects ◽  
Inhibitory Effects ◽  
Macrophage Recruitment ◽  
M2 Polarization ◽  
Brown Adipose ◽  
Major Burn

Abstract Introduction Severe burns are accompanied by a detrimental hypermetabolic stress response that can persist for years post-injury. Our previous work revealed that, under prolonged stress, white adipose tissue (WAT) adopts brown adipose-like traits in a process termed ‘browning’. This switch, characterized by the presence of uncoupling protein 1 (UCP1), is driven by the polarization of macrophages towards an M2 phenotype. Recently, we demonstrated that inhibiting lipolysis with the clinically approved drug, Acipimox, represses the burn-induced thermogenic activation of WAT. These findings raise the possibility that elevated rates of lipolysis may play a role in regulating the macrophage polarization state after major burn. However, the interconnection between post-burn lipolysis and inflammation remains unclear. In the present study, we investigated the mechanism underlying Acipimox’s inhibitory effects on burn-induced browning. Using a mouse model of thermal injury, we determine the metabolic effects of reducing WAT lipolysis on burn-induced macrophage recruitment and M2-polarization. Methods Adult C57BL/6 mice received a 30% total body surface area scald burn. Mice were then given daily intraperitoneal injections of APX (50 mg/Kg). On day 7 post-burn, the inguinal adipose tissue depot (iWAT) was harvested for histological analyses. Flow cytometry and F4/80 staining were used to assess adipose macrophage distribution and profile, and gene expression was analyzed via qPCR. Results APX administration significantly increased mitochondrial coupling, reflected by the decrease in UCP-1 (p< 0.05) and PGC-1a (p< 0.01) levels relative to the iWAT of untreated burn mice. F4/80 immunostaining of iWAT demonstrated decreased macrophage recruitment in Acipimox treated mice (p< 0.05). Flow cytometric analysis indicated decreased macrophage infiltration at 7 days in Acipimox treated mice (p< 0.05). Furthermore, iWAT from Acipimox treated mice demonstrated a pro-inflammatory profile, indicated by a greater distribution of TLR4 positive macrophages (p< 0.05). Conclusions Previously, we showed that the administration of Acipimox effectively suppressed PKA-mediated lipolysis and improved mitochondrial coupling in adipose tissue post-burn. Here, we elucidate the mechanism underlying these metabolic changes. Importantly, we show Acipimox exerts its inhibitory effects on burn-induced WAT browning by directly modulating macrophage recruitment and the M2-polarization state. Applicability of Research to Practice Our study highlights the critical role of lipolysis in mediating the key post-burn metabolic phenomena browning and inflammation. The data presented herein validate the pharmacological inhibition of lipolysis as a potentially powerful therapeutic strategy to counteract the detrimental metabolic effects induced by burn.

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.

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.

scholarly journals ChREBP-β regulates thermogenesis in brown adipose tissue

2020 ◽  
Vol 245 (3) ◽  
pp. 343-356 ◽  
Author(s):  
Chunchun Wei ◽  
Xianhua Ma ◽  
Kai Su ◽  
Shasha Qi ◽  
Yuangang Zhu ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Cold Exposure ◽  
Uncoupling Protein ◽  
Critical Role ◽  
Active Form ◽  
Negative Regulator ◽  
Mrna Levels ◽  
Brown Adipose ◽  
Metabolic Remodeling

Brown adipose tissue (BAT) plays a critical role in energy expenditure by uncoupling protein 1 (UCP1)-mediated thermogenesis. Carbohydrate response element-binding protein (ChREBP) is one of the key transcription factors regulating de novo lipogenesis (DNL). As a constitutively active form, ChREBP-β is expressed at extremely low levels. Up to date, its functional relevance in BAT remains unclear. In this study, we show that ChREBP-β inhibits BAT thermogenesis. BAT ChREBP-β mRNA levels were elevated upon cold exposure, which prompted us to generate a mouse model overexpressing ChREBP-β specifically in BAT using the Cre/LoxP approach. ChREBP-β overexpression led to a whitening phenotype of BAT at room temperature, as evidenced by increased lipid droplet size and decreased mitochondrion content. Moreover, BAT thermogenesis was inhibited upon acute cold exposure, and its metabolic remodeling induced by long-term cold adaptation was significantly impaired by ChREBP-β overexpression. Mechanistically, ChREBP-β overexpression downregulated expression of genes involved in mitochondrial biogenesis, autophagy, and respiration. Furthermore, thermogenic gene expression (e.g. Dio2, UCP1) was markedly inhibited in BAT by the overexpressed ChREBP-β. Put together, our work points to ChREBP-β as a negative regulator of thermogenesis in brown adipocytes.

scholarly journals The role of adipokines in developmental programming: evidence from animal models

2019 ◽  
Vol 242 (1) ◽  
pp. T81-T94 ◽  
Author(s):  
Clare M Reynolds ◽  
Mark H Vickers
Keyword(s):  
Adipose Tissue ◽  
Animal Models ◽  
Maternal Nutrition ◽  
Adult Life ◽  
Empirical Support ◽  
Later Life ◽  
Developmental Programming ◽  
Critical Periods ◽  
Reproductive Disorders ◽  
Wide Range

Alterations in the environment during critical periods of development, including altered maternal nutrition, can increase the risk for the development of a range of metabolic, cardiovascular and reproductive disorders in offspring in adult life. Following the original epidemiological observations of David Barker that linked perturbed fetal growth to adult disease, a wide range of experimental animal models have provided empirical support for the developmental programming hypothesis. Although the mechanisms remain poorly defined, adipose tissue has been highlighted as playing a key role in the development of many disorders that manifest in later life. In particular, adipokines, including leptin and adiponectin, primarily secreted by adipose tissue, have now been shown to be important mediators of processes underpinning several phenotypic features associated with developmental programming including obesity, insulin sensitivity and reproductive disorders. Moreover, manipulation of adipokines in early life has provided for potential strategies to ameliorate or reverse the adverse sequalae that are associated with aberrant programming and provided insight into some of the mechanisms involved in the development of chronic disease across the lifecourse.

Effect of maternal glucose infusion on brown adipose tissue and liver development in the neonatal lamb

1996 ◽  
Vol 8 (7) ◽  
pp. 1045 ◽  
Author(s):  
L Clarke ◽  
DC Andrews ◽  
MA Lomax ◽  
ME Symonds
Keyword(s):  
Adipose Tissue ◽  
Thyroid Hormones ◽  
Brown Adipose Tissue ◽  
Plasma Concentrations ◽  
Glucose Infusion ◽  
Late Gestation ◽  
Hepatic Glycogen ◽  
Liver Development ◽  
Brown Adipose ◽  
Maternal Glucose

The effect of maternal glucose infusion over the final 5-7 days of gestation in under-fed ewes on perirenal brown adipose tissue (BAT) and liver development in lambs over the first month of neonatal life was examined. During glucose infusion, higher maternal plasma concentrations of glucose and thyroid hormones, and lower plasma concentrations of non-esterified fatty acids and 3-hydroxybutyrate were observed, compared with saline-infused controls. These differences were not observed 1-1.5 h before parturition when plasma concentrations of glucose, lactate, cortisol and thyroid hormones all increased in control ewes. Lamb birthweight and liver and BAT weights were similar between groups, but lambs born to glucose-infused ewes had a higher hepatic glycogen content and greater iodothyronine 5'deiodinase activities in liver and BAT. The norepinephrine, epinephrine and dopamine contents were also greater in BAT sampled from lambs born to glucose infused ewes. Three lambs born to glucose-infused ewes failed to survive beyond the second week of life and exhibited abnormally low plasma triiodothyronine concentrations. It is concluded that maternal glucose infusion stimulates development of the fetal sympathetic nervous system during late gestation but this adaptation does not appear to improve postnatal survival.

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