Endocrine Abstracts

The global epidemic of obesity and type 2 diabetes has hastened the need to identify novel and efficacious therapies. Based upon parallels with Cushing’s syndrome, tissue specific cortisol excess, independent of circulating levels, has been suggested to have a crucial pathological role and may represent a potential treatment target. In key metabolic target tissues (liver, adipose and muscle), the endoluminal enzyme, 11β-hydroxysteroid dehydrogenase type 1 (11β-H...

The global epidemic of obesity and its associated complications has hastened the need with which we must understand both the patho-physiological process that contribute to its development, and also the urgency with which we need therapeutic solutions that offer clinically meaningful and sustained weight loss. There is clear evidence as to the beneficial impact of exercise upon health, in particular cardiovascular health, in normal weight and obese individuals as well as those ...

Polycystic ovary syndrome (PCOS) is one of the most prevalent conditions facing the clinical endocrinologist, affecting 5–10% of all women. The condition is characterized in part, by clinical and / or biochemical androgen excess. Despite its prevalence, the molecular mechanisms that contribute to its pathogenesis remain relatively poorly understood. Whilst androgen excess forms part of the diagnostic criteria, the source of the androgen excess is unclear, and ovarian, adr...

The global epidemic of obesity has heightened the need to understand the mechanisms that contribute to its pathogenesis and also to design and trial novel treatments. Patients with glucocorticoid (GC) excess, ‘Cushing’s syndrome’ share many phenotypic similarities to patients with simple obesity. GC availability to bind and activate the glucocorticoid receptor (GR) is controlled by the type 1 isoform of 11β-hydroxysteroid dehydrogenase (11β-HSD1) that ...

Non-alcoholic fatty liver disease (NAFLD), more recently renamed metabolic dysfunction associated steatotic liver disease (MASLD), is the most highly prevalent chronic liver condition and is associated with significant adverse outcomes, both through liver-specific morbidity and mortality, but perhaps more importantly, through adverse cardiovascular and metabolic outcomes. MASLD is a spectrum of disease, extending from simple steatosis, through to inflammation and fibrosis and ...

Introduction: The relationship between non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes is well-established. However, the precise impact of glucose control on the severity and progression of NAFLD remains largely unexplored. Currently, none of the non-invasive scoring systems used to assess NAFLD severity incorporate glucose control markers, such as glycated hemoglobin (HbA1c).Methods: Data were collected fr...

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. It represents a spectrum of disease, ranging from steatosis to non-alcoholic steatohepatitis, progressing to fibrosis, cirrhosis, and hepatocellular carcinoma. BAs, as well as their intermediary products (oxysterols), are metabolic modulators exerting their effects through activation of nuclear receptors (NRs), including the farnesoid-X- (FXR) and liver-X-receptors (LXR). Cruciall...

The hepatic enzyme 5β-reductase (AKR1D1) sits at the interface between two metabolic pathways, converting steroid hormones to their inactive 5β-reduced metabolites during steroid clearance, and as a step in the synthesis of bile acids from cholesterol. Both the steroid substrates and the bile acid products of AKR1D1 are potent hormones that regulate hepatic energy metabolism and inflammation. It is not known how these two functions are spatially organised within hepa...

Hepatocellular carcinoma (HCC) is the 6th most common form of cancer and the 4th most common cause of cancer related death. AKR1C1 is a member of the aldo-keto reductase 1C (AKR1C) subfamily and has important roles in steroid hormone metabolism and in reducing lipid peroxides. AKR1C1 is ubiquitously expressed, with high levels of expression in the liver. Studies have identified differential expression in HCC with high levels of AKR1C1 expression associate...

Dysbiosis of the gut microbiome contributes to the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Reduced diversity and composition of the microbiome are associated with increased intestinal barrier permeability, increased bacterial translocation and NAFLD progression. The ALIOS diet in rodents replicates many of the metabolic and histological features of NAFLD in humans and here we report the effect of the ALIOS diet on the gut microbiome. Male and female C57BL/6 ...