Brown adipose tissue (BAT) is essential to maintain body temperature. Its ability to convert chem... more Brown adipose tissue (BAT) is essential to maintain body temperature. Its ability to convert chemical energy in glucose and free fatty acids to heat is conferred by a unique protein, UCP‐1. BAT activity is greatest in children and adolescents, declining through adulthood. Blood glucose concentrations outside the normal nondiabetic range are common in type 1 diabetes and hyperglycaemia leads to insulin resistance in muscle and white adipose tissue, but whether this applies to BAT, is not known.
Hormone Molecular Biology and Clinical Investigation
The global prevalence of obesity and related cardiometabolic disease continues to increase throug... more The global prevalence of obesity and related cardiometabolic disease continues to increase through the 21st century. Whilst multi-factorial, obesity is ultimately caused by chronic caloric excess. However, despite numerous interventions focussing on reducing caloric intake these either fail or only elicit short-term changes in body mass. There is now a focus on increasing energy expenditure instead which has stemmed from the recent ‘re-discovery’ of cold-activated brown adipose tissue (BAT) in adult humans and inducible ‘beige’ adipocytes. Through the unique mitochondrial uncoupling protein 1 (UCP1), these thermogenic adipocytes are capable of combusting large amounts of chemical energy as heat and in animal models can prevent obesity and cardiometabolic disease. At present, human data does not point to a role for thermogenic adipocytes in regulating body weight or fat mass but points to a pivotal role in regulating metabolic health by improving insulin resistance as well as glucose...
Reproduction, fertility, and development, Jan 3, 2017
Intrauterine growth restriction in late pregnancy can contribute to adverse long-term metabolic h... more Intrauterine growth restriction in late pregnancy can contribute to adverse long-term metabolic health in the offspring. In the present study we used an animal (sheep) model of maternal dietary manipulation in late pregnancy, combined with exposure of the offspring to a low-activity, obesogenic environment after weaning, to characterise the effects on glucose homeostasis. Dizygotic twin-pregnant sheep were either fed to 60% of requirements (nutrient restriction (R)) or fed ad libitum (~140% of requirements (A)) from 110 days gestation until term (~147 days). After weaning (~3 months of age), the offspring were kept in either a standard (in order to remain lean) or low-activity, obesogenic environment. R mothers gained less weight and produced smaller offspring. As adults, obese offspring were heavier and fatter with reduced glucose tolerance, regardless of maternal diet. Molecular markers of stress and autophagy in liver and adipose tissue were increased with obesity, with gene expr...
Background - The emergence of brown adipose tissue (BAT) as a possible novel obesity prevention a... more Background - The emergence of brown adipose tissue (BAT) as a possible novel obesity prevention and treatment target has led to renewed interest in its physiology. The lack of an acceptable, safe, non-invasive method for repeated analysis is a significant barrier to in vivo human studies as the use of PET-CT in large prospective studies is limited by expense and ionising radiation exposure.We have developed a novel technique for measuring BAT activity using thermal imaging (TI)[1]. TI is a cheap, quick, non-invasive, valid and reproducible procedure acceptable to children as young as five years old[2]. We present here novel modifications to our original method.Method - As previously described[1,2] images centred on the anterior aspect of the neck were obtained using a thermal imaging camera (FLIR B425; FLIR Systems, Sweden) over a 25 minute period, at a rate of 6/minute. Following a period of acclimatisation, the participant's right hand was submerged in cold water (18°C±0.1°C),...
Brown adipose tissue is uniquely able to rapidly produce large amounts of heat through activation... more Brown adipose tissue is uniquely able to rapidly produce large amounts of heat through activation of uncoupling protein (UCP) 1. Maximally stimulated brown fat can produce 300 watts/kg of heat compared to 1 watt/kg in all other tissues. UCP1 is only present in small amounts in the fetus and in precocious mammals, such as sheep and humans; it is rapidly activated around the time of birth following the substantial rise in endocrine stimulatory factors. Brown adipose tissue is then lost and/or replaced with white adipose tissue with age but may still contain small depots of beige adipocytes that have the potential to be reactivated. In humans brown adipose tissue is retained into adulthood, retains the capacity to have a significant role in energy balance, and is currently a primary target organ in obesity prevention strategies. Thermogenesis in brown fat humans is environmentally regulated and can be stimulated by cold exposure and diet, responses that may be further modulated by phot...
This study investigated the developmental and nutritional programming of uncoupling protein-2 (UC... more This study investigated the developmental and nutritional programming of uncoupling protein-2 (UCP2), glucocorticoid receptor (GR) and 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) mRNA in the sheep lung from the time of uterine attachment to 6 months of age. The effect of maternal nutrient restriction on lung development was determined in early to mid gestation (i.e. 28-80 days gestation, period of maximal placental growth, and embryonic and pseudoglandular stages of fetal lung development) and late gestation (i.e. 110-147 days gestation, period of maximal fetal growth, and canalicular and saccular stages of fetal lung development). Fetal lungs were sampled at 80 and 140 days (term approximately 148 days) gestation, and sheep lungs at 1, 7, 30 days and 6 months. GR and 11betaHSD1 mRNA were maximal at 140 days gestation, whereas UCP2 mRNA peaked at 1 day of age and then declined with postnatal age. Maternal nutrient restriction in both early-to-mid and late gestation had n...
Journal of applied physiology (Bethesda, Md. : 1985), 2000
We examined the hypothesis that exogenous stimulation with physiological doses of 3,5,3'-trii... more We examined the hypothesis that exogenous stimulation with physiological doses of 3,5,3'-triiodothyronine (T(3)) and/or norepinephrine at birth can improve thermoregulation in near-term lambs delivered by cesarean section. This was achieved by investigating the effect of delivery temperature [i.e., warm (30( degrees )C) vs. cool (15( degrees )C) ambient temperatures] on hormonal stimulation on uncoupling protein-1 (UCP1) abundance in brown adipose tissue. In vivo measurements of temperature control (i. e., colonic temperature, oxygen consumption, and incidence of shivering) were made over the first 2.5 h after birth. Each lamb was injected with saline with or without T(3), norepinephrine, or T(3) plus norepinephrine. Irrespective of delivery temperature, abundance of UCP1 increased and incidence of shivering decreased by all hormonal treatments, but this only reduced the rate of decline in colonic temperature of cool-delivered lambs. Oxygen consumption was higher in cool-deliver...
We have previously shown that feeding 50 ml of colostrum can increase the thermogenic activity of... more We have previously shown that feeding 50 ml of colostrum can increase the thermogenic activity of brown adipose tissue (BAT) in newborn lambs maintained at a warm (30 degrees C) ambient temperature. This study further examines the effect of ambient temperature on BAT and thermoregulation by investigating the response to feeding 50 ml of water. Immediately after vaginal birth, lambs were placed in either a warm (30 degrees C) or cool (15 degrees C) environment a ambient temperature and measurements of colonic temperature and heat production were recorded for 6 h. Lambs were fed 50 ml of water when 5 h old. The level of guanosine 5'-diphosphate (GDP) binding was higher, but adrenaline content lower in BAT sampled from lambs maintained at 15 degrees C compared with those at 30 degrees C. Feeding was associated with an increase in colonic temperature and plasma concentrations of glucose and non-esterified fatty acids in lambs maintained at 15 degrees C only. In this group plasma con...
Adipocytes, traditionally thought to be passive reservoirs of surplus energy, are now recognized ... more Adipocytes, traditionally thought to be passive reservoirs of surplus energy, are now recognized as dynamic entities with varied metabolic and secretory properties. Adipocytes originate from mesodermal stem cells in a two-step process of commitment to adipocyte lineage, followed by terminal differentiation. The lineage diversifies to create three distinct types of cells – white, brown, and brown-in-white or ‘brite’ adipocytes.
Brown adipose tissue (BAT) is essential to maintain body temperature. Its ability to convert chem... more Brown adipose tissue (BAT) is essential to maintain body temperature. Its ability to convert chemical energy in glucose and free fatty acids to heat is conferred by a unique protein, UCP‐1. BAT activity is greatest in children and adolescents, declining through adulthood. Blood glucose concentrations outside the normal nondiabetic range are common in type 1 diabetes and hyperglycaemia leads to insulin resistance in muscle and white adipose tissue, but whether this applies to BAT, is not known.
Hormone Molecular Biology and Clinical Investigation
The global prevalence of obesity and related cardiometabolic disease continues to increase throug... more The global prevalence of obesity and related cardiometabolic disease continues to increase through the 21st century. Whilst multi-factorial, obesity is ultimately caused by chronic caloric excess. However, despite numerous interventions focussing on reducing caloric intake these either fail or only elicit short-term changes in body mass. There is now a focus on increasing energy expenditure instead which has stemmed from the recent ‘re-discovery’ of cold-activated brown adipose tissue (BAT) in adult humans and inducible ‘beige’ adipocytes. Through the unique mitochondrial uncoupling protein 1 (UCP1), these thermogenic adipocytes are capable of combusting large amounts of chemical energy as heat and in animal models can prevent obesity and cardiometabolic disease. At present, human data does not point to a role for thermogenic adipocytes in regulating body weight or fat mass but points to a pivotal role in regulating metabolic health by improving insulin resistance as well as glucose...
Reproduction, fertility, and development, Jan 3, 2017
Intrauterine growth restriction in late pregnancy can contribute to adverse long-term metabolic h... more Intrauterine growth restriction in late pregnancy can contribute to adverse long-term metabolic health in the offspring. In the present study we used an animal (sheep) model of maternal dietary manipulation in late pregnancy, combined with exposure of the offspring to a low-activity, obesogenic environment after weaning, to characterise the effects on glucose homeostasis. Dizygotic twin-pregnant sheep were either fed to 60% of requirements (nutrient restriction (R)) or fed ad libitum (~140% of requirements (A)) from 110 days gestation until term (~147 days). After weaning (~3 months of age), the offspring were kept in either a standard (in order to remain lean) or low-activity, obesogenic environment. R mothers gained less weight and produced smaller offspring. As adults, obese offspring were heavier and fatter with reduced glucose tolerance, regardless of maternal diet. Molecular markers of stress and autophagy in liver and adipose tissue were increased with obesity, with gene expr...
Background - The emergence of brown adipose tissue (BAT) as a possible novel obesity prevention a... more Background - The emergence of brown adipose tissue (BAT) as a possible novel obesity prevention and treatment target has led to renewed interest in its physiology. The lack of an acceptable, safe, non-invasive method for repeated analysis is a significant barrier to in vivo human studies as the use of PET-CT in large prospective studies is limited by expense and ionising radiation exposure.We have developed a novel technique for measuring BAT activity using thermal imaging (TI)[1]. TI is a cheap, quick, non-invasive, valid and reproducible procedure acceptable to children as young as five years old[2]. We present here novel modifications to our original method.Method - As previously described[1,2] images centred on the anterior aspect of the neck were obtained using a thermal imaging camera (FLIR B425; FLIR Systems, Sweden) over a 25 minute period, at a rate of 6/minute. Following a period of acclimatisation, the participant's right hand was submerged in cold water (18°C±0.1°C),...
Brown adipose tissue is uniquely able to rapidly produce large amounts of heat through activation... more Brown adipose tissue is uniquely able to rapidly produce large amounts of heat through activation of uncoupling protein (UCP) 1. Maximally stimulated brown fat can produce 300 watts/kg of heat compared to 1 watt/kg in all other tissues. UCP1 is only present in small amounts in the fetus and in precocious mammals, such as sheep and humans; it is rapidly activated around the time of birth following the substantial rise in endocrine stimulatory factors. Brown adipose tissue is then lost and/or replaced with white adipose tissue with age but may still contain small depots of beige adipocytes that have the potential to be reactivated. In humans brown adipose tissue is retained into adulthood, retains the capacity to have a significant role in energy balance, and is currently a primary target organ in obesity prevention strategies. Thermogenesis in brown fat humans is environmentally regulated and can be stimulated by cold exposure and diet, responses that may be further modulated by phot...
This study investigated the developmental and nutritional programming of uncoupling protein-2 (UC... more This study investigated the developmental and nutritional programming of uncoupling protein-2 (UCP2), glucocorticoid receptor (GR) and 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) mRNA in the sheep lung from the time of uterine attachment to 6 months of age. The effect of maternal nutrient restriction on lung development was determined in early to mid gestation (i.e. 28-80 days gestation, period of maximal placental growth, and embryonic and pseudoglandular stages of fetal lung development) and late gestation (i.e. 110-147 days gestation, period of maximal fetal growth, and canalicular and saccular stages of fetal lung development). Fetal lungs were sampled at 80 and 140 days (term approximately 148 days) gestation, and sheep lungs at 1, 7, 30 days and 6 months. GR and 11betaHSD1 mRNA were maximal at 140 days gestation, whereas UCP2 mRNA peaked at 1 day of age and then declined with postnatal age. Maternal nutrient restriction in both early-to-mid and late gestation had n...
Journal of applied physiology (Bethesda, Md. : 1985), 2000
We examined the hypothesis that exogenous stimulation with physiological doses of 3,5,3'-trii... more We examined the hypothesis that exogenous stimulation with physiological doses of 3,5,3'-triiodothyronine (T(3)) and/or norepinephrine at birth can improve thermoregulation in near-term lambs delivered by cesarean section. This was achieved by investigating the effect of delivery temperature [i.e., warm (30( degrees )C) vs. cool (15( degrees )C) ambient temperatures] on hormonal stimulation on uncoupling protein-1 (UCP1) abundance in brown adipose tissue. In vivo measurements of temperature control (i. e., colonic temperature, oxygen consumption, and incidence of shivering) were made over the first 2.5 h after birth. Each lamb was injected with saline with or without T(3), norepinephrine, or T(3) plus norepinephrine. Irrespective of delivery temperature, abundance of UCP1 increased and incidence of shivering decreased by all hormonal treatments, but this only reduced the rate of decline in colonic temperature of cool-delivered lambs. Oxygen consumption was higher in cool-deliver...
We have previously shown that feeding 50 ml of colostrum can increase the thermogenic activity of... more We have previously shown that feeding 50 ml of colostrum can increase the thermogenic activity of brown adipose tissue (BAT) in newborn lambs maintained at a warm (30 degrees C) ambient temperature. This study further examines the effect of ambient temperature on BAT and thermoregulation by investigating the response to feeding 50 ml of water. Immediately after vaginal birth, lambs were placed in either a warm (30 degrees C) or cool (15 degrees C) environment a ambient temperature and measurements of colonic temperature and heat production were recorded for 6 h. Lambs were fed 50 ml of water when 5 h old. The level of guanosine 5'-diphosphate (GDP) binding was higher, but adrenaline content lower in BAT sampled from lambs maintained at 15 degrees C compared with those at 30 degrees C. Feeding was associated with an increase in colonic temperature and plasma concentrations of glucose and non-esterified fatty acids in lambs maintained at 15 degrees C only. In this group plasma con...
Adipocytes, traditionally thought to be passive reservoirs of surplus energy, are now recognized ... more Adipocytes, traditionally thought to be passive reservoirs of surplus energy, are now recognized as dynamic entities with varied metabolic and secretory properties. Adipocytes originate from mesodermal stem cells in a two-step process of commitment to adipocyte lineage, followed by terminal differentiation. The lineage diversifies to create three distinct types of cells – white, brown, and brown-in-white or ‘brite’ adipocytes.
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Papers by Michael Symonds