Endocrine Abstracts

Idiopathic intracranial hypertension (IIH) is characterised by raised intracranial pressure (ICP) and papilloedema, diagnosed primarily in obese women of reproductive age, with the incidence rising with the global epidemic of obesity. Weight-loss lowers ICP and treats IIH. No mechanism explains the link between obesity and raised ICP. We hypothesise that adipose tissue from IIH patients has a metabolically distinct profile that contributes to raised ICP. Our previous data demo...

The study of humans carrying dominant negative mutations in PPAR gamma has contributed significantly to our understanding of its role in human physiology. To date, comparable studies of PPAR alpha have not been reported. Using a pooled approach, we undertook exon sequencing of PPARA in 11,848 adult participants of the Fenland study, a population-based cohort study with detailed metabolic phenotyping. Twenty-nine PPARA missense variants were detected (allelic ...

The intestinal epithelium (IE) is populated by different cell types each with a unique set of functions. Each cell type is derived from a common progenitor, the stem cell. The hierarchy of epithelial cell fate is transcriptionally regulated for example, Notch signalling defines secretory versus absorptive destiny. Peptide hormone producing enteroendocrine (EE) cells are scattered throughout the epithelium where they integrate complex nutrient signals and respond by promoting m...

Background: Empagliflozin is a sodium-glucose-cotransporter-2 that improves cardiovascular risk and weight loss in patients with type 2 diabetes. Polycystic ovary syndrome (PCOS) is associated with obesity and increased cardiovascular risk; therefore, empagliflozin may be of benefit in PCOS.Methods: A randomised, open-label study in 40 overweight and obese women with PCOS treated with either empagliflozin 25 mg or metformin 1500mg daily for 12 weeks....

Background: The presence of brown adipose tissue (BAT) in adults offers an opportunity to examine inflammatory factors that may affect metabolic function in states of obesity. Gut-derived lipopolysaccharide (LPS), which is elevated in obesity, and initiates the innate immune response in white adipose tissue, has not been fully studied in BAT. The interactions between LPS, TLR4 and ß3-adrenergic receptors in BAT is unknown. ß3-adrenergic receptor ligands as CL 316,243...

Vitamin B12 (B12) is an essential micronutrient required for optimal hematopoietic, neurologic and other several metabolic reactions. Longitudinal studies and animal models showed that low maternal vitamin B12 deficiency is associated with the maternal obesity, development of insulin resistance and metabolic syndrome phenotype suggesting the crucial role of B12 in adipose tissue function. Although the mechanisms underpinning metabolic disorders remain poorly defined, the patho...

Vitamin B12 (B12) is an essential micronutrient required for two key metabolic reactions. Longitudinal studies and animal models showed that B12-deficiency during pregnancy is associated with the maternal obesity, development of insulin resistance and metabolic syndrome phenotype. Although the mechanisms underpinning low B12 and metabolic disorders remain poorly defined, it’s becoming increasingly clear that lipid dysregulation is associated with obesity and co-morbiditie...

There is limited evidence for the role of screening for Cushing’s syndrome (CS). Patients referred to the specialist medical weight management service at Musgrove Park Hospital have routinely been screened for CS with either an overnight dexamethasone suppression test (ODST) or two 24hour urinary free cortisol (UFC) if evidence of dysglycaemia. We retrospectively analysed the results of all patients referred to the service between 2013–2016. 794 patients were seen as...

Background: The liver stores 10 μg cobalamin per gram protein and able to hold 50% (1–1.5 mg) of body’s B12. Making up the bulk of the liver, hepatocytes express receptors regulating cellular uptake of B12 in the liver. However, relationship between circulating and intracellular B12 levels as well as regulation of hepatic uptake of B12 is unexplored.Objective: To assess the regulation of cellular uptake and storage of B12 in hepatocytes in...

Background: Obstructive sleep apnoea (OSA) and polycystic ovary syndrome (PCOS) are associated with significant comorbidities and commonly coexist. The primary aim of this study was to examine the relationship between OSA and quality of life (QoL) in women with PCOS.Study design: Observational cross-sectional study.Methods: Women with PCOS were recruited from a single secondary care centre in the UK. PCOS was diagnosed according to...

Background: Metformin is utilized in clinical trials for treatment of non-alcoholic fatty liver disease (NAFLD) and obesity. Metformin increases AMP:ATP ratio activating AMP activated protein kinase-alpha (AMPKα), a mediator of fatty acid oxidation (FAO) in the liver. Meanwhile, prolonged oral metformin therapy in T2DM decreases vitamin B12(B12) in patients and evidence shows that low B12 dysregulates lipid levels. We therefore investigated whether low B12 impairs FAO ind...

Background: Prevalence of obesity and diabetes has increased significantly in the UAE over the last 40 years. Adenovirus 36 (Adv36) infection has been associated with obesity in several studies across different ethnic populations, and usually is associated with improved glucose tolerance.Objective: 1) Identify the prevalence of Adv36 seropositivity among adults living in the UAE.2) Investigate the association of Adv36 infection wit...

Background: Down Syndrome (DS) is the most common chromosomal abnormality. Obesity and type 1 diabetes mellitus (T1DM) are known to be more prevalent in patients with DS than the general population. Available data on the prevalence of type 2 diabetes mellitus (T2DM) in DS is scant.Objectives: This study aims to investigate the prevalence of obesity and diabetes mellitus (DM) in adults with DS seen in Imperial College London Diabetes Centre (ICLDC) in the...

Aim: To evaluate the feasibility of non-face to face (NFTF) contact in the follow-up for patients with thyrotoxicosis on carbimazole therapy.Background: While on carbimazole, achievement of a euthyroid state may involve multiple clinic appointments. We hypothesize by conducting these appointments in a NFTF setting, i.e. telephone consultation with trained nurse practitioner supported by an Endocrine consultant; a higher volume of consultations can occur ...

The enzyme 5β-reductase (AKR1D1) controls intra-cellular steroid hormone availability through hormone clearance. Additionally, it catalyses an essential step in bile acid (BA) synthesis. Disturbances in steroid hormones and BA metabolism have potent effects on metabolic health, therefore we hypothesize that AKR1D1 may play a role in metabolic homeostasis; the role of AKR1D1 in regulating glucose homeostasis and pancreatic function remains unexplored. We generated a global...

Background: Delivery of nutrient excess in obesity can disrupt protein folding in the endoplasmic reticulum (ER) within adipose tissue; this activates the unfolded protein response (UPR) and contributes to type 2 diabetes mellitus (T2DM) risk. Thus, the aims of this study were to utilise freeze-dried broccoli extract (BE) as a nutrient to mitigate such cellular damage in human adipocytes, understand the relevance of associated pathways, and create a mathematical model of the U...

Introduction: Angiopoietin-like proteins (ANGPTLs) are a family of 8 glycoproteins with pleiotropic effects in metabolism, angiogenesis, inflammation and cancer. ANGPTL3, 4 and 8 play major roles in regulating lipid levels, via inhibition of lipoprotein lipase. Increased serum ANGPTL3, 4, 8 levels are associated with obesity, diabetes, metabolic syndrome and fatty liver. Furthermore, cord blood ANGPTL8 is higher than in maternal serum, suggesting a role in fetal development an...

The role of brown adipose tissue (BAT) in pathological states of energy homeostasis and impaired adipocyte function, such as obesity has been a major area of research interest in recent years. Herein, we sought to determine the direct effects of adipokines, visfatin and leptin on BAT thermogenesis. The effects of mouse recombinant visfatin, nicotinamide mononucleotide (NMN) and leptin with or without FK866 were studied on differentiated T37i cells. Treated cells were analyzed ...

Glucocorticoid (Gc) excess, either from endogenous overproduction in disorders of the hypothalamic-pituitary-adrenal axis or exogenous medical therapy, is recognized to cause adverse metabolic side effects including obesity, hyperphagia, and hyperglycemia. The Gc receptor (GR) is widely expressed in the brain including the hypothalamus which is known to regulate energy balance. We have previously established through the administration of corticosterone (Cort) in the drinking w...

Background/aim: Patients with germline mutations in the tumor suppressor PTEN frequently develop single or multiple lipomas. PTEN antagonizes the phosphatidylinositide3-kinase/AKT/mechanistic target of rapamycin (PI3K/AKT/mTOR) pathway, which promotes cell proliferation and is involved in adipocyte differentiation. The aim of this study was to investigate the mechanisms leading to aberrant adipose tissue growth using PTEN knock-down cell models....

Introduction: Excessive consumption of free sugars (glucose and fructose) is linked to an increased risk of developing chronic metabolic diseases. Current knowledge of fructose metabolism has focussed on the liver where it is implicated in impaired insulin sensitivity, increased fat accumulation and dyslipidaemia. The long-term effects of elevated fructose consumption on human health are poorly defined and fructose metabolism in subcutaneous adipose tissue, the largest human f...

Background: Metformin is widely used for treatment of gestational diabetes mellitus. Metformin is considered safe in pregnancy but crosses the placenta. The limited available data of follow-up of children exposed to metformin in utero suggests potential for increased adiposity but mechanisms are unknown. As placental DNA methylation has been linked to later obesity and metformin causes global DNA methylation changes in cancer cell lines we hypothesised that this may be a candi...

Coupling metabolic processes to nutrient availability is essential for survival. The nuclear receptors PPARα and FXR regulate adaptive liver metabolism in the fasted-state and fed-state, respectively, through a complex mechanism that is incompletely understood. Here, we show that hepatic expression of the steroidogenic enzyme Cyp17al is strikingly regulated by feed-fast cycles via a repressive nuclear receptor cascade involving bile-acid:FXR signalling. Using both gain- a...

Background and Aim: Supplementation with precursors of nicotinamide adenine dinucleotide (NAD), was shown to be beneficial in preventing metabolic dysfunction in mice, which is induced by feeding a high fat diet. We compared the effect of nicotinamide riboside (NR) supplementationon whole-body energy metabolism and mitochondrial function in two widely used diet-induced obesity mouse models.Methods: Mice were fed a high fat diet (HFD, 60% fat) or standard...