Biomedical subjects

T Stephenson

Publications and source records attributed to T Stephenson.

At least 37 records · Page 2Linked to original sources

PubMed2005

Tissue-specific effects of leptin administration on the abundance of mitochondrial proteins during neonatal development.

Many tissues undergo a rapid transition after birth, accompanied by dramatic changes in mitochondrial protein function. In particular, uncoupling protein (UCP) abundance increases at birth in the lung and adipose tissue, to then gradually decline, an adaptation that is important in enabling normal tissue function. Leptin potentially mediates some of these changes and is known to promote the loss of UCP1 from brown fat but its effects on UCP2 and related mitochondrial proteins (i.e. voltage-dependent anion channel (VDAC) and cytochrome c) in other tissues are unknown. We therefore determined the effects of once-daily jugular venous administration of ovine recombinant leptin on mitochondrial protein abundance as determined by immunoblotting in tissues that do (i.e. the brain and pancreas) and do not (i.e. liver and skeletal muscle) express UCP2. Eight pairs of 1-day-old lambs received either 100 mug leptin or vehicle daily for 6 days, before tissue sampling on day 7. Administration of leptin diminished UCP2 abundance in the pancreas, but not the brain. Leptin administration had no affect on the abundance of VDAC or cytochrome c in any tissue examined. In leptin-administered animals, but not controls, UCP2 abundance in the pancreas was positively correlated with VDAC and cytochrome c content, and UCP2 abundance in the brain with colonic temperature. In conclusion, leptin administration to neonatal lambs causes a tissue-specific loss of UCP2 from the pancreas. These effects may be important in the regulation of neonatal tissue development and potentially for optimising metabolic control mechanisms in later life.

Animals↗

PubMed2005

On-site treatment of a motorway service area wastewater using a package sequencing batch reactor (SBR).

A sequencing batch reactor (SBR) treating the effluent of a motorway service station in the south of England situated on a major tourist route was investigated. Wastewater from the kitchens, toilets and washrooms facilities was collected from the areas on each side of the motorway for treatment on-site. The SBR was designed for a population equivalent (p.e.) of 500, assuming an average flow of 100 m3/d, influent biochemical oxygen demand (BOD) of 300 mg/l, and influent suspended solids (SS) of 300 mg/l. Influent monitoring over 8 weeks revealed that the average flow was only 65 m3/d and the average influent BOD and SS were 480 mg/l and 473 mg/l respectively. This corresponded to a high sludge loading rate (F:M) of 0.42 d(-1) which accounted for poor performance. Therefore the cycle times were extended from 6 h to 7 h and effluent BOD improved from 79 to 27 mg/l.

Bioreactors↗

PubMed2005

Dinitrogen oxide detection for nitrification failure early warning systems.

Experiments were conducted in order to establish whether N2O could be used to predict nitrification failure (through non-invasive means). Previous research had shown a strong correlation between N2O gas and NH3 in the effluent, giving rise to the possibility N2O can be used as an indicator for failure in the nitrification process. Two pilot-scale activated sludge plants were used, each with two lanes. The smaller consisted of a 601 aeration tank and a 201 clarifier; the larger pilot plant had an aeration tank of 3151 and a clarifier of 1001. The small pilot plant experiments showed that N2O gas was given off almost immediately from O2 deprivation/NH3 shock loads, but did not follow the expected trend of the time lag of NH3 in the effluent. This led to further investigation in the hydrodynamics and mixing characteristics of aeration basins, where a second larger pilot plant was used. Further experiments were conducted of high NH3 loadings and O2 deprivation, showed that work of was reproducible. However, it was also shown that with partial nitrification failure, a different N2O response of a continual rise was observed.

Ammonia↗

PubMed2004

Activation of IP prostanoid receptors prevents cardiomyocyte hypertrophy via cAMP-dependent signaling.

The antihypertrophic action of angiotensin-converting enzyme inhibitors in the heart results partly from local potentiation of bradykinin. We have demonstrated that the antihypertrophic action of bradykinin is mediated by the release of nitric oxide from endothelium and elevation of cardiomyocyte cGMP. Whether other paracrine factors derived from the coronary endothelium, such as prostacyclin (PGI2), may act to prevent hypertrophy has not been explored. In the vasculature, activation by PGI2 of IP and EP1 prostanoid receptors elicits vasodilatation (via cAMP-dependent signaling) and vasoconstriction, respectively. The present objective was to determine whether IP prostanoid receptor activation has antihypertrophic actions in adult rat cardiomyocytes (ARCM). The selective IP agonist cicaprost (1 microM) virtually abolished the increase in [3H]phenylalanine incorporation (a marker of hypertrophy) induced either by endothelin-1 (ET-1; 60 nM, n = 10, P < 0.005) or by angiotensin II (1 microM, n = 6, P < 0.005). Cicaprost also inhibited ET-1 induction of c-fos mRNA expression, an additional marker of hypertrophy in ARCM (n = 5, P < 0.005). In the absence of hypertrophic stimuli, cicaprost alone did not significantly influence either marker. The antihypertrophic actions of cicaprost were mimicked by the dual IP/EP1 agonist iloprost (1 microM) in the presence of the EP1 antagonist AH-6809 (3 microM). Furthermore, cicaprost modestly but significantly increased cardiomyocyte cAMP content by 13 +/- 6% (P < 0.05, n = 4), and the antihypertrophic effect of cicaprost was lost in the presence of the cAMP-dependent protein kinase inhibitor H-89 (1 microM, n = 5, P < 0.05). However, ET-1 also induced increases in the activity of the intracellular growth signals ERK1 (by 3-fold) and ERK2 (by 5-fold) in ARCM, and these were not inhibited by cicaprost (P < 0.01, n = 5). Activation of IP receptors thus represents a novel approach to prevention of hypertrophy, and this effect is linked to cAMP-dependent signaling.

Angiotensin II↗

PubMed2004

Nutritional manipulation of fetal adipose tissue deposition and uncoupling protein 1 messenger RNA abundance in the sheep: differential effects of timing and duration.

A range of epidemiological and experimental studies have indicated that suboptimal nutrition at different stages of gestation is associated with an increased prevalence of adult hypertension, cardiovascular disease, and obesity. The timing of prenatal nutrient restriction is important in determining postnatal outcomes-including obesity. The present study, aimed to determine the extent to which fetal adiposity and expression of the key thermogenic protein, uncoupling protein (UCP)1, are altered by restriction of maternal nutrient intake imposed during four different periods, starting from before conception. Maternal nutrient intake was restricted from 60 days before until 8 days after mating (periconceptional nutrient restriction; R-C), from 60 days before mating and throughout gestation (R-R), from 8 days gestation until term (C-R), or from 115 days gestation until term. Fetal perirenal adipose tissue (PAT) was sampled near to term at approximately 143 days. UCP1 mRNA, but not protein, abundance in PAT was increased in fetuses in the R-R group (C-C 63 +/- 18; R-C 83 +/- 43; C-R 103 +/- 38; R-R 167 +/- 50 arbitrary units (P < 0.05)). In contrast, the abundance of UCP1 mRNA, but not protein, in fetal PAT was decreased when maternal nutrition was restricted from 115 days gestation. The major effect of maternal nutrient restriction on adipose tissue deposition occurred in the C-R group, in which the proportion of fetal fat was doubled, whereas maternal nutrient restriction from 115 days gestation reduced fetal fat deposition. In conclusion, there are differential effects of maternal and therefore fetal nutrient restriction on UCP1 mRNA expression and fetal fat mass and these effects are dependent on the timing and duration of nutrient restriction.

Adipose Tissue↗

PubMed2004

Programming of adult cardiovascular function after early maternal undernutrition in sheep.

The prenatal nutritional environment influences the subsequent risk of hypertension in adulthood. Animal studies have used, generally, the rat as a model species to illustrate the association between maternal nutrient intake and blood pressure in the resulting adult offspring. No study to date has shown programming of adult cardiovascular function in the sheep through maternal dietary intervention. We therefore fed pregnant sheep to either 100% recommended intake from day 0 of gestation to term [ approximately 147 days gestational age (dGA); controls n = 8] or to 50% recommended intake from day 0 to 95 dGA and thereafter to 100% intake (NR; n = 9). Sheep lambed naturally, offspring were weaned at 16 wk, and the male offspring were reared on pasture until 3 yr of age. At this time, cardiovascular catheters were inserted under halothane anesthesia and sheep were allowed 2-4 days recovery. Basal cardiovascular status and pressor responses to infusion of norepinephrine, angiotensin II, and captopril were then assessed alongside basal plasma concentrations of glucose, cortisol, and leptin. NR sheep were of similar birth weight to controls but at 3 yr of age had higher blood pressure before, but not after, feeding. Peripheral sensitivity to vasoconstrictor infusion was similar between dietary groups, although a reflex bradycardia was not apparent in NR sheep during norepinephrine infusion. Circulating leptin correlated well with fat mass and increased more after vasoconstrictor infusion in NR sheep. In conclusion, early NR has been shown to program aspects of cardiovascular control and adipocyte function in adult sheep.

Algorithms↗

PubMed2004

Hormonal and nutritional regulation of adipose tissue mitochondrial development and function in the newborn.

Growth, development, and maturation of adipose tissue in the fetus can determine both survival at birth as well as having longer term consequences for adult disease. The mitochondrial proteins uncoupling protein (UCP) 1, voltage dependent anion channel (VDAC), and cytochrome c have an important role in cellular energy regulation. Activity of these proteins is particularly important during the transition from fetal to neonatal life when cellular energy requirements are at near maximal rates. The regulation of these proteins by endocrine factors is highly complex and may be dependent on both fetal number and maternal nutrition. The cytokine hormones leptin and prolactin have well established functions in energy regulation and lactation respectively. However, recent data proposes a role in regulation of mitochondrial proteins, particularly UCP1, and thermogenesis. Cortisol is an adrenal hormone with a critical role in fetal tissue maturation, especially the lung. It has now been shown to influence the abundance of UCP1 in the fetus, a role that may in part be regulated by the metabolically active thyroid hormone triiodothyronine. A greater understanding of the regulation of mitochondrial proteins within adipose tissue by endocrine and nutritional factors is likely to be important in preventing neonatal morbidity and mortality. It could also add substantially to our understanding of pathological conditions such as obesity and non-insulin dependent diabetes.

Adipose Tissue, Brown↗

PubMed2004

Feasibility of biological aerated filters (BAFs) for treating landfill leachate.

Ammonia can be removed from landfill leachate using aerobic biological treatment processes. The biological aerated filter (BAF) combines biological treatment and subsequent biomass separation in one reactor providing a small footprint alternative to conventional systems. Leachate from an operational landfill was found to be aerobically treatable using the OECD recommended Modified Zahn-Wellens test. This leachate was used as feed to a pilot-scale BAF at influent chemical oxygen demand (COD) and ammoniacal-nitrogen concentrations of 765 mg l(-1) and 568 mg l(-1) respectively. During an initial period of stable operation without pH control, 33 %w/w of influent ammonia was removed. The reactor pH was 9.2 with little conversion to total oxidized nitrogen (< 45 mg l(-1)), this removal was accounted for primarily by air stripping. In a second period of stable operation, the reactor pH was reduced to pH 7.2 and ammonia removal increased to 97 %w/w with a concomitant increase in effluent nitrite concentration to an average of 524 mg l(-1). Biological aerated filters (BAFs) can be used to nitrify landfill leachates though onward denitrification of nitrite-nitrogen and COD polishing is required to reach typical discharge consent standards.

Ammonia↗

PubMed2004

The impact of presenting problem based guidelines for children with medical problems in an accident and emergency department.

AIMS: To evaluate the impact of presenting problem based guidelines in managing children with either diarrhoea (with or without vomiting) or seizure (with or without fever). METHODS: This prospective observational study with an intervention was based on a paediatric accident and emergency (A&E) department in Nottingham. All patients (either GP or self referred) were acute attenders aged 0-15 years, with a medical presenting problem during 4 months in the spring of 1997 and 1999. Five hundred and thirty-one diarrhoea attendances (292 before guideline implementation and 239 after) and 411 seizure attendances (212 before guideline implementation and 199 after) were recorded. Evidence based and consensus ratified guidelines developed for the study were implemented using care pathway documentation. Process (documentation, time in the department, investigations, treatment) and outcome (admission to hospital, returns to A&E) data were collected from case notes. RESULTS: The percentage of children investigated with blood tests fell significantly (haematology requests in diarrhoea presentations from 11% to 4%, biochemistry in seizure presentations from 29% to 17%). Intravenous infusions in diarrhoea presenters fell (9% to 1%), and more appropriate oral fluids were used. Management time in A&E was reduced (diarrhoea presenters: median of 55-40 minutes, seizure presenters: 80-55 minutes, but remained static for other presenting problems). Marked improvements in documentation were seen. Admission rates for diarrhoea attenders increased (27% to 34%) but remained the same for seizure (69% v 73%). CONCLUSIONS: The implementation of a presenting problem based guideline as a care pathway was associated with improvements in the quality of care by: improved documentation; reduced invasive investigations; more appropriate treatment, and reduced time spent in A&E.

Adolescent↗

PubMed2004

Ever deeper and wider: incorporating sustainability into a practitioner oriented engineering curriculum.

Whilst valuable debates about how best to plan, promote, and evaluate sustainable futures for our communities are conducted by governments and NGOs at global gatherings, there is an equal, and possibly more pressing, need to inspire and equip engineering graduates with the means to design and implement the required solutions. However, incorporation of sustainability as a subject into existing syllabi is problematic, primarily because of the need for students to acquire both holistic and context specific skills. This contribution first considers the reasons why we should be concerned with the integration of sustainability concepts into graduate and post-graduate curricula. We then go on to discuss the significance of cross-disciplinary thinking and skills as a key element of sustainability relevant knowledge. Finally, we report the design and deployment, within a water engineering degree course, of a post-graduate module in "Process design for sustainability". The implications of our experiences for the theory and practice of engineering education are examined and suggestions made concerning best practice.

Conservation of Natural Resources↗

PubMed2003

Maternal nutrient restriction during placental growth, programming of fetal adiposity and juvenile blood pressure control.

Epidemiological and experimental studies have demonstrated that maternal undernutrition during pregnancy is associated with abnormal placental growth. In sheep, maternal nutrient restriction over the period of rapid placental growth (30-80 days) restricts placentome growth. Then following adequate nutrition up to term (147 days), placental mass is greater in association with a higher total abundance of the predominant placental glucose transporter-1. The resulting lambs are larger at birth, have heavier kidneys with an increased expression of the glucocorticoid-responsive type 1 angiotensin II receptor. Near to term, these fetuses possess more adipose tissue, the endocrine sensitivity of which is markedly enhanced. For example, the abundance of mRNA for 11beta-hydroxysteroid dehydrogenase type 1, which catalyses the conversion of cortisone to bio-active cortisol is increased. This is associated with a higher abundance of both leptin and glucocorticoid receptor mRNA. At 6 months of age, the juvenile offspring of nutrient restricted ewes have lower resting blood pressure that was positively correlated with plasma cortisol concentration, suggesting their blood pressure could be more strongly driven by circulating cortisol. These offspring also exhibited a greater pressor response to vasoconstrictor challenges, but showed no difference in vasodilatory response. At this age, the kidney weight was similar between groups, but the abundance of cytochrome c in kidney mitochondria was enhanced in lambs born to nutrient restricted ewes that could indicate increased mitochondrial activity. Reduced maternal nutrition during the period of rapid placental growth may therefore contribute to hypertension in later life through physiological and vascular adaptations during fetal life.

Adipose Tissue↗

PubMed2003

Ontogeny and nutritional manipulation of mitochondrial protein abundance in adipose tissue and the lungs of postnatal sheep.

The present study examined the ontogeny of mitochondrial protein abundance in adipose tissue and lungs over the first month of life in the sheep and the extent to which this may be altered by maternal undernutrition during the final month of gestation. The ontogeny of uncoupling protein (UCP), voltage-dependent anion channel (VDAC) and cytochrome c abundance were determined in adipose tissue and lungs sampled from near-term fetuses and young sheep aged 4 h, 1, 7 and 30 d. In adipose tissue, the abundance of UCP1, VDAC and cytochrome c all peaked at 1 d of age and then decreased by 30 d of age, at which stage the brown adipose tissue-specific UCP1 was no longer detectable but UCP2 was clearly abundant. For the lungs, however, UCP2 and VDAC abundance both peaked 7 d after birth and then decreased by 30 d of age. During postnatal development, therefore, a marked change in mitochondrial protein abundance occurs within both adipose tissue and lungs. Maternal nutrient restriction had no effect on lamb growth or tissue weights at 30 d of age but was associated with increased abundance of UCP2 and VDAC but not cytochrome c in both adipose tissue and lungs. These mitochondrial adaptations within both adipose tissue and the lungs of offspring born to previously nutrient-restricted mothers may compromise adipose tissue and lung function during periods of environmental stress.

Adipose Tissue↗

PubMed2003

Prolactin, prolactin receptor and uncoupling proteins during fetal and neonatal development.

Uncoupling proteins (UCP) 1 and 2 are members of the subfamily of inner mitochondrial membrane carriers. UCP1 is specific to brown adipose tissue (BAT), where it is responsible for the rapid production of heat at birth. In fetal sheep UCP1 is first detectable at approximately 90 d of gestation; its abundance increases with gestational age and peaks at the time of birth. The mRNA and protein for both the long and short form of the prolactin (PRL) receptor (PRLR) are also highly abundant in BAT. Enhanced PRLR abundance in late gestation is associated with an increase in the abundance of UCP1. This relationship between PRLR and UCP is not only present in BAT. Similar findings are now reported in the pregnant ovine uterus, where PRLR abundance reaches a maximum just before that of UCP2. However, the role of PRLR in BAT remains undetermined. Rat studies have shown that PRL administration throughout pregnancy results in offspring with increased UCP1 at birth. Studies in newborn lambs have shown that administration of PRL (2 mg/d) causes an acute response, increasing colonic temperature in the first hour by 1 degrees. This increased colonic temperature is maintained for the first 24h of life, in conjunction with enhanced lipolysis. After 7 d of treatment there is no difference in the abundance of UCP1 but an increase in UCP1 activity; this effect may be mediated by an increase in lipolysis. Taken together these findings suggest that PRL could be an important endocrine factor during pregnancy and early postnatal life.

Adipose Tissue, Brown↗

PubMed2003

Characterization of plasma inhibin forms in fertile and infertile men.

BACKGROUND: The reciprocal relationship between plasma FSH and inhibin B generally reflects the state of spermatogenesis but data in some settings indicate further complexity in their relationship. Inhibin circulates as a range of higher molecular weight (mol wt) forms of varying bioactivity such that the serum profile of inhibin forms may differ between normal men and those with varying types of spermatogenic failure. The aim of this study was to establish if the inhibin B mol wt distribution was altered in men with infertility. METHODS: The mol wt profiles of inhibin B and free alpha-subunit were determined in plasma of fertile (n = 11) and infertile (n = 17) men using a combined immunoaffinity chromatography, preparative SDS-PAGE and electro-elution procedure and fractions assayed using ELISAs for inhibin B, total inhibin (all forms containing the alpha-subunit) and free alpha-subunit. RESULTS: Inhibin B was identified as precursor (60-65 k) and mature (26-30 k) forms in plasma in similar proportions (29%) in fertile men and oligospermic men (25%), but was undetectable in azoospermic men. The free alpha-subunit detected by the pro-alphaC ELISA was identified as both the precursor and processed (pro-alphaC) forms with similar proportions in fertile (8%) and all infertile (4-14%) men. The pro-alphaC ELISA did not detect the precursor forms of inhibin B in plasma while the inhibin B ELISA detected all total inhibin forms following removal of pro-containing forms by immunoabsorption. CONCLUSIONS: (i) the proportions of precursor inhibin B and alpha-subunit forms in the circulation are unchanged in men with spermatogenic disorders indicating there is no alteration of the Sertoli cell inhibin secretory pattern; (ii) these fractionation studies indicate that pro-alphaC and inhibin B ELISAs specifically detect the free alpha-subunit and inhibin B forms present in male plasma.

Adult↗

PubMed2003

An evidence and consensus based guideline for the management of a child after a seizure.

OBJECTIVE: An evidence and consensus based guideline for the management of the child who presents to hospital having had a seizure. It does not deal with the child who is still seizing. The guideline is intended for use by junior doctors, and was developed for this common problem (5% of all paediatric medical attenders) where variation in practice occurs. OPTIONS: Assessment, investigations (biochemistry, lumbar puncture, serum anticonvulsant levels, EEG in particular), and/or admission are examined. OUTCOMES: The guideline aims to direct junior doctors in recognising those children who are at higher risk of serious intracranial pathology including infection, and conversely to recognise those children at low risk who are safe to go home. EVIDENCE: A systematic review of the literature was performed. Articles were identified using the electronic data bases Medline (from 1966 to June 1998), Embase (from 1980 to June 1998) and Cochrane (to June 1998), and selected if they investigated the specified clinical question. Personal reviews were excluded. Selected articles were appraised, graded, and synthesised qualitatively. Statements of recommendation were made. CONSENSUS: An anonymous, postal Delphi consensus development was used. A national panel of 30 medical and nursing staff regularly caring for these children were asked to grade their agreement with the statements generated. They were sent the relevant original publications, the appraisals, and literature review. On the second and third rounds they were asked whether they wished to re-grade their agreement in the light of other panellists' responses. Consensus was defined as 83% of panellists agreeing with the statement. Recommendations in brief: For afebrile seizures all children should have their blood pressure recorded, but no other investigations are routine although a seizing or somnolent child should have blood glucose measured; all children under 1 year should be admitted. For seizures with fever, clinical signs indicating the need to treat as meningitis are given. Children should be admitted if they are under 18 months old, have had a complex seizure, or after pretreatment with antibiotics. VALIDATION: The guideline has undergone implementation and evaluation in a paediatric accident and emergency department, the results of which will be published separately. Only one alteration was made to the guideline as a result of this validation process, which is included here.

Algorithms↗

PubMed2003

Neonatal transfers by advanced neonatal nurse practitioners and paediatric registrars.

OBJECTIVE: To evaluate the safety and practicality of using advanced neonatal nurse practitioners (ANNPs) to lead acute neonatal transfers. DESIGN: Comparison of transport times, transport interventions, and physiological variables, covering the first four complete years of operating a transport service that uses ANNPs and specialist paediatric registrars (SpRs) interchangeably. SETTING: Tertiary neonatal transport service. PATIENTS: The first 51 transfers of sick infants under 28 days of age by an ANNP led transport team into Nottingham compared with the next consecutive SpR led transfer after each ANNP led one. MAIN OUTCOME MEASURES: Transport times; interventions and support given during stabilisation for transfer and during transfer; condition on completion of transfer, assessed from blood glucose, systolic blood pressure, pH, oxygenation, and temperature. RESULTS: The ANNP led team responded more rapidly to requests for transfer and took longer to stabilise babies. The groups undertook similar numbers of procedures during stabilisation, and there were no differences in the ventilatory and other support that infants needed in transit. The infants transferred by the doctor led group had worse values for pH (doctor led, 7.31 (6.50-7.46); ANNP led, 7.35 (7.04-7.50), p = 0.02) and PaO(2) (doctor led, 6.7 (2.4-13.1); ANNP led, 8.7 (3.5-17.0); p = 0.008) before transfer (all values median (range)). Comparisons of the infant's condition before and after transfer showed a significant improvement in temperature for the infants transferred by ANNP led teams (36.8 degrees C (34.0-37.8) v 37.0 degrees C (34.6-38.0), p = 0.001) and in oxygen saturation (96% (88-100) v 98% (92-100), p = 0.01). There were no differences between the ANNP and doctor led groups in the values obtained for any variable after transfer. CONCLUSIONS: Clinical condition on completion of transport is similar for babies transferred by ANNP and doctor led teams. ANNP led transport appears to be practical and safe.

England↗

PubMed2003

Maternal endocrine adaptation throughout pregnancy to nutritional manipulation: consequences for maternal plasma leptin and cortisol and the programming of fetal adipose tissue development.

Maternal nutrient restriction at specific stages of gestation has differential effects on fetal development such that the offspring are programmed to be at increased risk of adult disease. We investigated the effect of gestational age and maternal nutrition on the maternal plasma concentration of leptin and cortisol together with effects on fetal adipose tissue deposition plus leptin, IGF-I, IGF-II ligand, and receptor mRNA abundance near to term. Singleton bearing ewes were either nutrient restricted (NR; consuming 3.2-3.8 MJ/d of metabolizable energy) or fed to appetite (consuming 8.7-9.9 MJ/d) over the period of maximal placental growth, i.e. between 28 and 80 d gestation. After 80 d gestation, ewes were either fed to calculated requirements, consuming 6.7-7.5 MJ/d, or were fed to appetite and consumed 8.0-10.9 MJ/d. Pregnancy resulted in a rise in plasma leptin concentration by 28 d gestation, which continued up to 80 d gestation when fed to appetite but not with nutrient restriction. Plasma cortisol was also lower in NR ewes up to 80 d gestation, a difference no longer apparent when food intake was increased. At term, irrespective of maternal nutrition in late gestation, fetuses sampled from ewes NR in early gestation possessed more adipose tissue, whereas when ewes were fed to appetite throughout gestation, fetal adipose tissue deposition and leptin mRNA abundance were both reduced. These changes may result in the offspring of NR mothers being at increased risk of obesity in later life.

Adaptation, Physiological↗

PubMed2003

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

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.

Adipose Tissue, Brown↗