The effect of maternal arginine supplementation on the development of the thermogenic program in the ovine fetus

2014 ◽  
Vol 54 (10) ◽  
pp. 1843 ◽  
Author(s):  
S. McCoard ◽  
N. Wards ◽  
J. Koolaard ◽  
M. Senna Salerno

Brown adipose tissue (BAT) is a specialised fat store that is metabolised by the newborn lamb to ensure effective adaptation to the cold challenge of the extra-uterine environment. Increasing BAT reserves therefore has the potential to increase neonatal thermogenesis and survival. It is established that arginine supplementation can increase fetal BAT stores but the biological mechanisms involved are unclear. The objective of this study was to test the hypothesis that increased fetal BAT stores resulting from maternal arginine supplementation is mediated by activation of the thermogenic program. Brown adipose tissue was collected from fetuses of ewes supplemented with arginine from 100 to 140 days of gestation. Increased peri-renal fat stores in fetuses from arginine-supplemented ewes was associated with an increase in uncoupling protein 1 (UCP-1) and PRD1-BF-1-RIZ1 homologous domain containing protein-16 expression, but not proliferator-activated receptor gamma or proliferator-activated receptor gamma-co-activator-1α in BAT. The activity of UCP-1 is regulated by hormones including cortisol and thyroid hormones. Cortisol level in fetuses from supplemented sheep was 68% greater than those from control ewes, indicating that cortisol may control upregulation of UCP-1 expression in the ovine neonate. The DNA and RNA concentration in BAT of both groups suggest that increased peri-renal fat stores is not associated with an increase in cell number or number of ribosomes, but rather an increase in the size of individual fat cells. Collectively, these results indicate that maternal arginine supplementation during mid to late gestation improved the thermoregulatory ability of lambs and this could potentially increase their survival in early life.

2001 ◽  
Vol 29 (2) ◽  
pp. 80-85 ◽  
Author(s):  
T. Stephenson ◽  
H. Budge ◽  
A. Mostyn ◽  
S. Pearce ◽  
R. Webb ◽  
...  

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.


1996 ◽  
Vol 8 (6) ◽  
pp. 995 ◽  
Author(s):  
SJ Schermer ◽  
JA Bird ◽  
MA Lomax ◽  
DA Shepherd ◽  
ME Symonds

The effect of fetal thyroidectomy on thermoregulation in newborn lambs was investigated. Seven of 14 lambs born normally at term were thyroidectomized at Day 127 of gestation. Colonic temperature and oxygen consumption were measured during non-rapid eye movement sleep 6-45 h after birth. All lambs were then killed and perirenal brown adipose tissue was sampled for measurement of thermogenic activity (guanosine diphosphate binding), uncoupling protein and lipid contents. Thyroidectomized lambs tended to have a mean colonic temperature 2.35 degrees C lower (P = 0.067) than controls and two became hypothermic (i.e. colonic temperature < 35 degrees C). Thyroidectomized lambs exhibited lower rates of oxygen consumption (P = 0.05) and an increased incidence of shivering thermogenesis. The perirenal adipose tissue of these lambs had a lower thermogenic activity (P < 0.01), less uncoupling protein (P < 0.01) and higher lipid content (P = 0.072) compared with intact controls. It is concluded that fetal thyroidectomy results in a decreased ability of newborn lambs to utilize nonshivering thermogenesis in brown adipose tissue as well as increasing the incidence of hypothermia. These changes are associated with decreased synthesis of uncoupling protein and functional development of brown adipose tissue in the late gestation fetus.


1997 ◽  
Vol 77 (6) ◽  
pp. 871-883 ◽  
Author(s):  
Lynne Clarke ◽  
Michael J. Bryant ◽  
Michael A. Lomax ◽  
Michael E. Symonds

AbstractWe examined the effect of maternal chronic cold exposure, induced by winter-shearing ewes 4 weeks before their predicted lambing date, on brown adipose tissue (BAT) and liver development in lambs. Fetuses were sampled from under-fed (60% of energy requirements for maintenance and pregnancy of an unshorn ewe) shorn or unshorn ewes at 126,140 and 145 d of gestation. Lambs were sampled from ewes within 2 h of birth. Throughout gestation fetal body, BAT and liver weights were similar in shorn and unshorn groups. The level of GDP binding to mitochondrial uncoupling protein remained low throughout gestation, but increased dramatically after birth. Lambs born to shorn ewes possesd more mitochondrial protein and exhibited a significantly higher total thermogenic activity in BAT. Type I iodothyronine 5 deiodinas(EC 3.8.1.4) activity in BAT peaked at birth, as did hepatic iodothyronine Sdeiodinase activity and was significantly greater in lambs born to under-fed shorn ewes, which exhibited a higher plasma triiodothyronine concentration. Chronic maternal adaptations to prolonged cold exposure appear to enable pregnant ewes to compensate for the negative effects of under-feeding on fetal growth and development


1994 ◽  
Vol 269 (10) ◽  
pp. 7435-7438
Author(s):  
D.L. Murdza-Inglis ◽  
M. Modriansky ◽  
H.V. Patel ◽  
G. Woldegiorgis ◽  
K.B. Freeman ◽  
...  

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Haiying Zhou ◽  
Bo Wan ◽  
Ivan Grubisic ◽  
Tommy Kaplan ◽  
Robert Tjian

Brown adipose tissue (BAT) plays an essential role in metabolic homeostasis by dissipating energy via thermogenesis through uncoupling protein 1 (UCP1). Previously, we reported that the TATA-binding protein associated factor 7L (TAF7L) is an important regulator of white adipose tissue (WAT) differentiation. In this study, we show that TAF7L also serves as a molecular switch between brown fat and muscle lineages in vivo and in vitro. In adipose tissue, TAF7L-containing TFIID complexes associate with PPARγ to mediate DNA looping between distal enhancers and core promoter elements. Our findings suggest that the presence of the tissue-specific TAF7L subunit in TFIID functions to promote long-range chromatin interactions during BAT lineage specification.


2021 ◽  
Author(s):  
Mingsheng Ye ◽  
Liping Luo ◽  
Qi Guo ◽  
Guanghua Lei ◽  
Chao Zeng ◽  
...  

Brown adipose tissue (BAT) is emerging as a target to beat obesity through the dissipation of chemical energy to heat. However, the molecular mechanisms of brown adipocyte thermogenesis remain to be further elucidated. Here, we show that KCTD10, a member of the polymerase delta-interacting protein 1 (PDIP1) family, was reduced in BAT by cold stress and a β3 adrenoceptor agonist. Moreover, KCTD10 level increased in the BAT of obese mice, and KCTD10 overexpression attenuates uncoupling protein 1 (UCP1) expression in primary brown adipocytes. BAT-specific KCTD10 knockdown mice had increased thermogenesis and cold tolerance protecting from high fat diet (HFD)-induced obesity. Conversely, overexpression of KCTD10 in BAT caused reduced thermogenesis, cold intolerance, and obesity. Mechanistically, inhibiting Notch signaling restored the KCTD10 overexpression suppressed thermogenesis. Our study presents that KCTD10 serves as an upstream regulator of notch signaling pathway to regulate BAT thermogenesis and whole-body metabolic function.


1995 ◽  
Vol 268 (1) ◽  
pp. R183-R191 ◽  
Author(s):  
A. M. Strack ◽  
M. J. Bradbury ◽  
M. F. Dallman

Brown adipose tissue (BAT) contains glucocorticoid receptors; glucocorticoids are required for maintaining differentiated BAT in culture. These studies were performed to determine the effects of corticosterone on BAT thermogenic function and lipid storage. Rats were adrenalectomized and given subcutaneous corticosterone pellets in concentrations that maintained plasma corticosterone constant across the range of 0-20 micrograms/dl or were sham adrenalectomized. All variables were examined 5 days after surgery and corticosterone replacement. Measures of BAT function-thermogenic capacity [guanosine 5'-diphosphate (GDP) binding and uncoupling protein (UCP; a BAT-specific thermogenic protein)] and storage (BAT wet wt, protein, and DNA levels) were made. Plasma hormones (corticosterone, adrenocorticotropic hormone, insulin, 3,3',5-triiodothyronine, and thyroxine were measured. Corticosterone significantly affected BAT thermogenic measures: UCP content and binding of GDP to BAT mitochondria decreased with increasing corticosterone; GDP binding characteristics in BAT from similarly prepared rats examined by Scatchard analysis showed that maximum binding (Bmax) and dissociation constant (Kd) decreased with increasing corticosterone dose. BAT DNA was increased by adrenalectomy and maintained at intact levels with all doses of corticosterone; BAT lipid storage increased dramatically at corticosterone values higher than the daily mean level in intact rats. Histologically, the number and size of lipid droplets within BAT adipocytes increased markedly with increased corticosterone. White adipose depots were more sensitive to circulating corticosterone concentrations than were BAT depots and increased in weight at levels of corticosterone that were at or below the daily mean level of intact rats. We conclude that, within its diurnal range of concentration corticosterone acts to inhibit nonshivering thermogenesis and increase lipid storage.(ABSTRACT TRUNCATED AT 250 WORDS)


Sign in / Sign up

Export Citation Format

Share Document