Searchable abstracts of presentations at key conferences in endocrinology

ea0077p198 | Metabolism, Obesity and Diabetes | SFEBES2021

Corticosterone excess alters metabolic rate in male and female C57BL/6J mice

Heaselgrave Samuel , Heising Silke , Morgan Stuart , Morton Nicholas , Lavery Gareth

Introduction: Glucocorticoids are vital for regulating metabolic processes, as well as use in medical treatments. However chronic glucocorticoid excess is known to cause negative metabolic effects including hyperglycaemia, muscle atrophy and fat accumulation. The effect on energy metabolism and metabolic rate remains undefined and merits investigation in both male and female mice.Methods: 20 male and 20 female C57BL/6J mice were randomly assigned to a co...

ea0021p180 | Diabetes and metabolism | SFEBES2009

Impact of glucocorticoids upon lipogenesis and β-oxidation in skeletal muscle

Morgan Stuart , Gathercole Laura , Stewart Paul , Smith Dave , Tomlinson Jeremy

Glucocorticoid excess is characterized by increased adiposity, skeletal myopathy and insulin resistance. Although there is a strong inverse correlation between intramuscular triglyceride (IMTG) levels and insulin sensitivity, the impact of glucocorticoids upon the processes that regulate skeletal muscle lipid metabolism has not been explored.Mouse C2C12 skeletal myocytes were grown to confluence and differentiated into myotubes in chemically defined medi...

ea0013p179 | Diabetes, metabolism and cardiovascular | SFEBES2007

A characterisation of novel lipase expression and glucocorticoid regulation of lipolysis in human adipose tissue

Gathercole Laura , Bujalska Iwona , Morgan Stuart , Stewart Paul , Tomlinson Jeremy

Glucocorticoids (GC) have potent actions upon human adipose tissue, promoting adipocyte differentiation, inhibiting preadipocyte proliferation and inducing lipolysis to generate free fatty acids (FFA) and glycerol through a putative action upon hormone sensitive lipase (HSL). FFA have been strongly implicated in the pathogenesis of insulin resistance, yet the molecular mechanisms that cause GC induced lipolysis are not clear. Recently, several novel lipases have been identifie...

ea0086p155 | Adrenal and Cardiovascular | SFEBES2022

Glucocorticoid Excess Disrupts the NAD+ Metabolome Within Skeletal Muscle in Male and Female C57BL/6J Mice

Heising Silke , Heaselgrave Samuel , Morgan Stuart , Kabli Ali , Doig Craig , Tsintzas Kostas , Lavery Gareth

Introduction: Glucocorticoid excess (GE) causes severe metabolic dysfunction within skeletal muscle (SM) which includes reduced muscle accrual and increased proteolysis. The NAD+ metabolome is crucial for SM health and metabolic function, however, whether this is disrupted by GE remains unknown.Methods: Male and female C57BL/6J mice (n=12) were treated with a vehicle control or corticosterone (100 mg/l) ad libitum via drinking water for 3 weeks ...

ea0041oc2.5 | Receptors & Signalling | ECE2016

11β-HSD1 is a regulator of brown adipose tissue function and mediates stress adaptation in glucocorticoid excess

Doig Craig , Morgan Stuart , Philp Andrew , Tomlinson Jeremy , Stewart Paul , Lavery Gareth

Glucocorticoids (GC) are critical to stress adaptation but in excess (Cushing’s syndrome) drive metabolic dysfunction. 11β-hydroxysteroid dehydrogenase type 1(11β-HSD1) amplifies intracellular GC signaling with 11β-HSD1KO mice protected from the side-effects of GC excess. Brown adipose tissue (BAT) function is impaired by GC’s, which repress UCP1 and beta-adrenergic stimulated thermogenesis. Identifying mechanisms regulating BAT function is important a...

ea0034oc3.4 | Steroids | SFEBES2014

Pre-receptor glucocorticoid metabolism across human ageing: the impact of gender and menopausal status

Hassan-Smith Zaki , Morgan Stuart , Sherlock Mark , Hughes Beverly , Lavery Gareth , Tomlinson Jeremy , Stewart Paul

Introduction: There is growing evidence that 11β-HSD1 expression/activity increases with age in key target tissues including adipose tissue, bone, and skin, implicating local amplification of glucocorticoids in the pathophysiology of related disease. We have previously shown that 11β-HSD1KO mice are protected from both the adverse metabolic effects of excess glucocorticoids and age-associated muscle weakness. We investigated changes in global activity and skeletal mu...

ea0034p267 | Obesity, diabetes, metabolism and cardiovascular | SFEBES2014

11β HSD1KO mice resist aged associated decline in markers of brown adipose tissue function

McCabe Emma , Doig Craig , Morgan Stuart , Larner Dean , Tomlinson Jeremy , Stewart Paul , Lavery Gareth

The primary function of brown adipose tissue (BAT) is to use lipids to generate heat through uncoupling of oxidative phosphorylation in mitochondria. Glucocorticoids (GC) have a negative effect upon BAT through inhibition of uncoupling protein 1 (UCP1) expression. Similarly, it has been reported that BAT levels decline with age and have been linked to age related accumulation of body fat, leading to the idea that improving BAT function during ageing could have a beneficial rol...

ea0031oc1.3 | Young Endocrinologists prize session | SFEBES2013

11β-HSD1KO mice are protected from glucocorticoid dependent age-associated muscle atrophy

Hassan-Smith Zaki , Morgan Stuart , Bujalska Iwona , Abrahams Lianne , Cooper Mark , Lavery Gareth , Stewart Paul

Glucocorticoids (GCs) are prescribed for their anti-inflammatory and immunosuppressive properties. However, they have significant side-effects including a decline in muscle mass and function which has similarities to age related sacropaenia. Within skeletal muscle 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) converts 11-dehydrocorticosterone (11DHC) to active corticosterone (CORT) amplifying local GC action. We hypothesise that 11β-HSD1 mediated intramyoce...

ea0028oc4.2 | Steroid | SFEBES2012

Age-dependent increase in the expression/activity of 11β-HSD1 in key metabolic tissues may underpin the ageing phenotype notably sarcopenia

Morgan Stuart , Sherlock Mark , Lavery Gareth , Hassan-Smith Zaki , Abrahams Lianne , Stewart Paul

The pathophysiological effects of glucocorticoid (GC) excess (Cushing’s syndrome) are similar to the aging phenotype. As such, we hypothesise that age-related changed in body composition (central obesity, reduced bone density, reduced muscle mass and skin thinning), and resultant chronic disease (type 2 diabetes, osteoporosis, sarcopenia and heart disease) may be caused by increased GC exposure with age. However, circulating GC’s show little change with advancing age...

ea0028p307 | Steroids | SFEBES2012

Adipose depot specific regulation of insulin signalling by glucocorticoids

Gathercole Laura , Morgan Stuart , Bujalska Iwona , Nasiri Maryam , Stewart Paul , Tomlinson Jeremy

Intra-abdominal adiposity is associated with insulin resistance and increased cardiovascular morbidity and mortality. Consequently, there is a need to identify factors involved in adipose tissue distribution. Patients with glucocorticoid (GC) excess develop a classic phenotype characterized by central, but not peripheral, obesity. Differences in gene expression between omental (om) and subcutaneous (sc) adipose tissue have been described, however, the molecular mechanisms unde...