Endocrine Abstracts

Non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of the metabolic syndrome encompasses a spectrum of conditions from hepatic steatosis through to cirrhosis; obesity is a known risk factor. It remains unclear why intra-hepatocellular fat starts to accumulate, but it is likely to involve an imbalance between fatty acid delivery to the liver, fatty acid synthesis and oxidation within the liver and triglyceride export from the liver. Studying hepatic metabolism...

The liver is a relay station for fatty acid metabolism. Perturbations in hepatic fatty acid metabolism have the potential to impact widely on metabolic health. The accumulation or loss of liver fat (hepatocyte triacylglycerol (TG)) represents the balance between input pathways and removal pathways. In health these pathways must be closely balanced; imbalance will lead to changes in liver fat content. The concept of hepatic fatty acid partitioning is that fatty acids within the...

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...

Background: Pathological accumulation of intrahepatocellular triglyceride (IHTG) is the first stage non-alcoholic fatty liver disease (NAFLD), which encompasses a spectrum of disease from simple steatosis through to cirrhosis. Dietary interventions have demonstrated alterations in dietary fat quantity and quality affect IHTG content; diets rich in saturated compared to unsaturated fat increase IHTG accumulation to a greater extent. Studying the underlying mechanisms in viv...

Background: Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of diseases starting with pathological accumulation of intrahepatocellular triglyceride (TG) (i.e. steatosis), which can progress to steatohepatitis (NASH) and cirrhosis. Insulin resistance is often associated with the development of steatosis and disease progression however, the underlying mechanisms for this are poorly defined. A major challenge in modelling human NAFLD disease progression is the la...

Introduction: Palmitoleate, a proposed adipose tissue (AT)-derived lipokine, has been suggested to contribute to glucose homeostasis. However, data relating to the association between circulating palmitoleate and markers of insulin sensitivity in humans are equivocal. Recently, AT-derived fatty acid-hydroxy fatty acids (FAHFAs) have also been suggested to play a role in glucose homeostasis by increasing glucose uptake in AT. Again, data is conflicting for the association betwe...

Introduction: In vitro skeletal muscle cell models are vitally important for investigating the molecular mechanisms of skeletal muscle in metabolic and endocrine diseases, such as obesity and type 2 diabetes. Culture media for skeletal muscle cells can often contain glucose concentrations (GC) five times higher than what’s considered normal in fasting human plasma, thus is not representative of the in vivo environment. Hyperglycaemia in culture media may...

Introduction: Obstructive sleep apnea (OSA) affects up to 20% of a Western population and is associated with non-alcoholic fatty liver disease and type 2 diabetes (T2D). OSA is characterized by intermittent episodes of hypoxia (IH) that occur during sleep. It is not yet known if IH is directly linked to insulin resistance within key metabolic target tissues (adipose; liver and skeletal muscle) and what the potential underlying mechanism may be. It has been suggested that indiv...

Primary human hepatocytes are considered the ‘gold standard’ to explore metabolic phenotype within the liver, however they come with limitations, such as donor variability, lack of proliferation and rapid phenotype loss. The human hepatoma cell line, HepG2, has been used extensively in cell-based metabolic studies but there are significant limitations including their malignant origin and inherent low rates of triglyceride secretion. The aim of this study was to inves...

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...