Michael E. Symonds

Effect of maternal cold exposure on brown adipose tissue and thermogenesis in the neonatal lamb.

1. This study examines the effect of chronic cold exposure during pregnancy, induced by winter shearing twin‐bearing ewes 4 weeks before predicted lambing date, on O2 consumption and CO2 production during non‐rapid‐eye‐movement (REM) sleep in lambs maintained for at least 1 h at warm (28‐18 degrees C) and cold (14‐5 degrees C) ambient temperatures at 1, 4, 14 and 30 days of age. This was combined with measurement of the thermogenic activity (GDP binding to uncoupling protein in mitochondrial preparations) of perirenal adipose tissue from lambs immediately after birth and at 33 days of age. 2. Lambs born from shorn (cold‐exposed) ewes were 15% heavier (P < 0.01) and possessed 21% (P < 0.01) more perirenal adipose tissue that contained 40% more protein and mitochondrial protein than unshorn (P < 0.05) controls. Total GDP binding in perirenal adipose tissue was 40% greater (P < 0.05) in lambs born from shorn ewes but there was no difference in lipid content of this tissue between the two groups. 3. At 1 day of age, lambs born from shorn ewes exhibited a 16% higher (P < 0.05) rate of O2 consumption (per kilogram bodyweight) at the warm temperature and a 40% greater metabolic response to the cold ambient temperature. All lambs born from shorn ewes responded to cold exposure without shivering (i.e. via non‐shivering thermogenesis) whilst shivering was measured in four out of seven lambs in the unshorn group. These differences had disappeared by 4 days of age as a result of a 25% increased (P < 0.01) rate of O2 consumption in the warm in lambs born from unshorn ewes and a 20% decrease (P < 0.05) in the response to the cold in lambs from shorn ewes. Shivering during cold exposure was measured in six out of nine lambs born from shorn ewes indicating a rapid alteration in thermoregulatory responses to cold during the first few days of life. 4. The levels of GDP binding and mitochondrial protein in perirenal adipose tissue fell by one‐third in both groups of lambs during the first 33 days of life whereas lipid content either increased or was unchanged. This indicated that brown adipose tissue (BAT) was developing the characteristics of white adipose tissue.(ABSTRACT TRUNCATED AT 400 WORDS)

The effect of shearing on the energy metabolism of the pregnant ewe.

1. Metabolizable energy (ME) intakes, heat production, non-protein respiratory quotient (NPRQ) and the plasma concentrations of glucose, non-esterified fatty acids (NEFA), 3-hydroxybutyrate, insulin, growth hormone (GH) and cortisol were measured in shorn and unshorn pregnant ewes. 2. Lamb birth-weight was 17% higher from shorn ewes despite similar ME intakes in the two groups. Shearing resulted in a significant decrease in the digestibility of dry matter and energy. 3. Both shorn and unshorn ewes were found to be in positive nitrogen balance and negative energy balance. Heat production was 28% higher in shorn ewes. This increase in heat production in the shorn group could be completely accounted for by an increase in the oxidation of fatty acids as measured using the NPRQ values. 4. Despite an apparent increase in the use of fat as an energy source there were no effects of shearing on the mean plasma concentrations of NEFA, 3-hydroxybutyrate, GH and cortisol. 5. Measurements made at 1 h intervals for 24 h indicated a tendency for the concentrations of glucose to be increased and insulin decreased in shorn ewes, particularly, between 6 and 11 h after feeding. 6. It is concluded that shearing pregnant ewes at 8 weeks before lambing results in a chronic increase in energy requirements which are met by oxidizing body fat depots. The cold stress induced by shearing may also inhibit insulin secretion resulting in increased plasma glucose concentrations. The effects of shearing on energy metabolism in the ewe are discussed in relation to the nutrient supply for the developing fetus.

Lipid metabolism in shorn and unshorn pregnant sheep.

The aim of the present study was to determine how the long-term metabolic adaptations to winter shearing of the pregnant ewe result in significant changes in the rates of lipid mobilization and utilization of non-esterified fatty acids (NEFA) in comparison with unshorn controls. Continuous infusions of [1-14C]palmitic acid, [2-3H]glycerol and NaH14CO3 were used to measure whole-body lipid metabolism in fed (estimated metabolizable energy (ME) intake 9.54 MJ/d) and under-fed (estimated ME intake of 3 MJ/d), shorn and unshorn sheep over the final 4 weeks of pregnancy. Whole-body carbon dioxide, estimated heat production, total NEFA entry and oxidation rates were all significantly higher in fed shorn ewes compared with unshorn controls, even though there was no difference in the arterial plasma NEFA concentration. These differences may be mediated via an increase in the plasma concentrations of thyroid hormones in shorn animals. As a result of under-feeding any significant differences in lipid metabolism between shorn and unshorn groups were removed. In all sheep the mean total NEFA entry rate as measured using [1-14C]palmitic acid was 3.4 times the value obtained using [2-3H]glycerol. It is concluded that when sheep are fed on a diet from which no more than half the required ME for late pregnancy is obtained, then lipolysis of body fat depots occurs via the incomplete breakdown of adipose tissue triglycerides. This effect is significantly greater in the fed shorn pregnant ewe which exhibits higher entry and oxidation rates of NEFA.

Influence of Thyrotrophin-Releasing Hormone on Thermoregulation in Newborn Lambs

This study examined the effect of thyrotrophin-releasing hormone (TRH) administration on thermoregulation in the newborn. Twin lambs were either delivered near-term by caesarean section or born vaginally at term. Colonic temperature, O2 consumption, CO2 production, breathing and heart rates, plus plasma thyroid hormone and nonesterified fatty acid (NEFA) concentrations and thermogenic activity (i.e. GDP binding) of brown adipose tissue (BAT) were measured. In caesarean section delivered lambs colonic temperature decreased rapidly after birth, a response that was greater in the group designated for TRH treatment, in which colonic temperature fell to below 36.0°C at 80 min of life, prior to TRH administration. At this age colonic temperature had been restored to a mean of 38.70°C in controls. TRH had no influence on the composition or thermogenic activity of BAT. The incidence of shivering was not influenced by TRH, but treated lambs maintained a higher rate of O2 consumption and ventilation compared with controls after colonic temperature had been restored to 38.56°C. TRH appeared to promote fat oxidation as O2 consumption remained unchanged and CO2 production declined by a greater rate in treated lambs, resulting in a lower respiratory quotient compared to controls. Heart rate and plasma concentrations of NEFA increased following TRH administration although this did not result in values greater than controls. Normothermic lambs born vaginally had BAT with a greater thermogenic activity, higher plasma thyroid hormone and NEFA concentrations compared with caesarean section delivered lambs, but a thermogenic response was not observed to TRH despite a rise in thyroid hormone concentrations. In conclusion, TRH can improve thermoregulation, an effect that could be linked to an increase in fat oxidation.

Manipulation of Brown Adipose Tissue Development in Neonatal and Postnatal Lambs

In precocious mammalian species such as man and sheep which are not protected from hypothermia by huddling in a nest, the ability to alter metabolic rale in response to changes in ambient temperature at birth is a prerequisite for survival. The principal tissue involved in metabolic adaptation to the extra-uterine environment is brown adipose tissue (BAT), which has the ability to rapidly generate large amounts of heat and also convert thyroxine to triiodothyronine (T3) the dominant hormone regulating metabolic rate (1). An apparent failure to utilize BAT during neonatal and postnatal development is associated with unexpected death (1) and may be an important factor contributing to annual lamb mortality of 1–4 million in the British sheep industry. Therefore an improved understanding of the factors regulating the thermogenic function of BAT at birth and during the first month of life will aid in the manipulation of lamb thermogenic activity to improve survival rate.