Searchable abstracts of presentations at key conferences in endocrinology

ea0038p198 | Obesity, diabetes, metabolism and cardiovascular | SFEBES2015

Vascular dysfunction in horses with insulin resistance

Morgan Ruth , Keen John , Walker Brian , Hadoke Patrick

Background: Vascular impairment, most commonly due to endothelial dysfunction, is associated with cardiovascular risk in humans with obesity, insulin resistance or Cushing’s syndrome. Similar endocrine disorders in horses, resulting in insulin resistance, are associated with laminitis, a dysfunction of the vasculature supplying the hooves, the mechanism of which is unclear. We hypothesised that horses with insulin resistance have both local and systemic evidence of vascul...

ea0034p208 | Obesity, diabetes, metabolism and cardiovascular | SFEBES2014

Abnormal glucocorticoid metabolism in horses with metabolic syndrome

Morgan Ruth , Hadoke Patrick , Walker Brian , Keen John

Activation of the hypothalamic–pituitary–adrenal (HPA) axis and altered tissue glucocorticoid action in obesity and metabolic syndrome has been attributed to altered peripheral cortisol metabolism. In human obesity, cortisol clearance is increased with up-regulation of A-ring reductases and down-regulation of cortisol-regenerating 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in liver, while in adipose tissue 11β-HSD1 is up-regulated. Rodent studi...

ea0025p145 | Diabetes, metabolism and cardiovascular | SFEBES2011

Diet-induced obesity with metabolic dysfunction does not alter vascular function or remodelling in young C57Bl/6 mice

Dakin Rachel , Drake Amanda , Walker Brian , Seckl Jonathan , Hadoke Patrick

Obesity is associated with metabolic and vascular dysfunction. Many models have shown insulin resistance reduces endothelium-dependent vasodilation but this is also seen in obese subjects with normal glucose tolerance. There is also evidence of increased response to vascular injury in obese animals, although the mechanisms underpinning this are not fully understood. This study used a mouse model of diet-induced obesity (DIO) to address the hypothesis that obesity causes metabo...

ea0021p185 | Diabetes and metabolism | SFEBES2009

Diet-induced obesity in C57Bl/6 mice is associated with sex-specific changes in glucocorticoid metabolism

Dakin Rachel , Hadoke Patrick , Seckl Jonathan , Walker Brian , Drake Amanda

Although obesity affects men and women, the risks of associated metabolic disturbances (e.g. type 2 diabetes) differ between the sexes. Altered peripheral glucocorticoid metabolism may underpin the metabolic consequences of obesity; however, most research exploring this has focused on male animals. This study used a mouse model to investigate the hypothesis that alterations in glucocorticoid metabolism caused by diet-induced obesity (DIO) will be more profound in males than in...

ea0086p300 | Adrenal and Cardiovascular | SFEBES2022

Using mass spectrometry imaging to study the lipidome of atherosclerotic plaques

Ntshangase Sphamandla , Khan Shazia , Kaczynski Jakub , Newby David , Hadoke Patrick , Andrew Ruth

Atherosclerotic cardiovascular disease (ASCVD) is a chronic inflammatory disorder characterised by the gradual build-up of plaques in the arterial wall. Unstable plaques are more dangerous than stable plaques as they are prone to rupture and obstruct blood flow, resulting in heart attacks and strokes. Lipids play a key role in plaque progression, yet their exact involvement remains elusive. We hypothesise that stable or unstable plaques will have distinct spatial lipid phenoty...

ea0038oc4.3 | Diabetes and cardiometabolic complications | SFEBES2015

5α-tetrahydrocorticosterone exhibits topical anti-inflammatory action with limited adverse effects on angiogenesis

Gastaldello Annalisa , Livingstone Dawn E , Tsang Nicola , Walker Brian R , Hadoke Patrick W , Andrew Ruth

Background: The 5α-reduced glucocorticoid, 5α-tetrahydrocorticosterone (5α-THB), displays a dissociated steroid profile exhibiting anti-inflammatory effects in a murine model of thioglycollate-induced peritonitis but failing to induce adverse metabolic effects caused by corticosterone. We assessed the topical anti-inflammatory properties of 5α-THB in a model of irritant dermatitis. Given the adverse effects of steroids on cutaneous wound healing, we also in...

ea0032p336 | Developmental Endocrinology | ECE2013

Effects of pharmacological and genetic manipulation of glucocorticoids during early development of the zebrafish embryo

Wilson Kathryn , Matrone Gianfranco , Tucker Carl , Hadoke Patrick , Kenyon Christopher , Mullins John , Denvir Martin

Background: The effects of glucocorticoids (GC) on the developing zebrafish embryo (Zfe) are poorly characterised. We have assessed the effects of pharmacological and genetic manipulation of cortisol and glucocorticoid receptors (GR) on global development and stress response during the first 120 hpf.Methods: Cortisol production was modulated by inhibiting the enzyme 11b hydroxylase using morpholino gene knockdown (MO) or incubation in the drug metyrapone...

ea0031oc1.2 | Young Endocrinologists prize session | SFEBES2013

Macrophage-specific 11β-hydroxysteroid dehydrogenase type 1 deficiency promotes angiogenesis but impairs resolution of K/BxN serum induced arthritis

Zhang Zhenguang , Coutinho Agnes , Hadoke Patrick , Salter Donald , Seckl Jonathan , Chapman Karen

Chronic inflammatory disease is often accompanied by angiogenesis and fibrosis. Glucocorticoids (GCs) exert anti-inflammatory and anti-angiogenic effects, in which macrophages are a major target. Local endogenous GC action is controlled by 11β-hydroxysteroid dehydrogenase (11β-HSD), with the type 1 isozyme, 11β-HSD1 converting inactive GCs into active forms. Mice deficient in 11β-HSD1 have a phenotype consistent with reduced glucocorticoid action, including...

ea0025p156 | Diabetes, metabolism and cardiovascular | SFEBES2011

Attenuated atherosclerosis in 11β-hydroxysteroid dehydrogenase type 1 deficient ApoE−/− mice is associated with reduced aortic VCAM-1 expression and reduced MCP-1 in the visceral fat

Kipari Tiina , Man Tak-Yung , Hadoke Patrick , Savill John , Chapman Karen , Seckl Jonathan

11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) regenerates glucocorticoids in intact cells, converting inert cortisone into active cortisol. We have previously shown attenuated atherosclerosis development, reduced plasma monocyte chemoattractant protein-1 (MCP-1) and reduced macrophage/T cell infiltration within atherosclerotic lesions in 11β-HSD1−/−×ApoE−/− double knock-out (DKO) mice fed western diet (WD)....

ea0021p182 | Diabetes and metabolism | SFEBES2009

Deficiency in 11β-hydroxysteroid dehydrogenase type 1 reduces systemic inflammation and inflammatory cell infiltration in atherosclerotic lesions of ApoE−/− mice

Kipari Tiina , Man Tak-Yung , Hadoke Patrick , White Christopher , Chapman Karen , Seckl Jonathan

High plasma levels of glucocorticoids cause metabolic disease (central obesity, hypertension, diabetes) and increase risk of cardiovascular disease. 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) regenerates glucocorticoids in intact cells, converting inert cortisone (11-dehydrocorticosterone in rodents) into active cortisol (corticosterone in rodents). Recent work has shown the pathological importance of elevated adipose tissue 11β-HSD1 expression in develo...