Endocrine Abstracts

Background: Dysfunctional endoplasmic reticula (ER) and mitochondria contribute to the pathogenesis of obesity and type 2 diabetes mellitus (T2DM). This may, in part, be facilitated by cross-talk between the two organelles during conditions of nutrient excess such as obesity, however the potential impact of ER stress on mitochondrial function has not been well studied. This study investigated whether induction of ER stress in human adipocytes may contribute to mitochondrial dy...

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...

Background: Human cohorts and animal models provide compelling evidence suggesting the role of vitamin B12 in modulating the risk of diabetes and adiposity via developmental programming. We recently demonstrated that neonates born to mothers with low B12 levels in pregnancy have adverse cord blood lipid profile and in vitro studies in human adipocytes with low B12 showed increased cholesterol biosynthesis. Therefore, we hypothesized that vitamin B12 deficiency may pla...

Background/objectives: Fibroblast growth factor 21 (FGF21) is a potent hormone known to reduce glycaemia and improve insulin resistance with anti-obesity effects. Although mainly secreted in the liver, adipose tissue is considered an important target for its function. Whilst FGF21 has been shown to be expressed in murine adipose tissue, studies in human adipose tissue are lacking. Therefore our aim was to examine the expression of FGF21, FGF21 receptor-1 (FGFR1), βKlotho ...

Adipose tissue (AT) plays a central role in integrating energy metabolism and glucose homeostasis. It is the major site of fatty acid storage as triglycerides and is body’s largest cholesterol pool. In AT cholesterol is mostly found in its free, non-esterified form. There is accumulating evidence that cholesterol imbalance in AT is closely associated with adipocyte dysfunction and obesity-mediated metabolic complications, including low levels of high-density lipoprotein c...

Background: Adipose tissue (AT) plays a central role in obesity-related complications such as cardiovascular diseases, insulin resistance, and type two diabetes. A comprehensive understanding of the molecular mechanisms underlying adipocyte formation is of both fundamental and clinical relevance. It has been reported that UPR pathway, IRE1α-XBP1 regulates hepatic lipogenesis and the role of this pathway in adipogenesis in murine adipocytes has also been confirmed. Our tea...

Mitochondria are essential for synthesising ATP required for cellular metabolism. Mitochondria are able to alter their morphology and abundance through the balance of fission and fusion genes. T2DM is often accompanied by a metabolic syndrome within the individual. The aim of my PhD is to investigate whether metabolic dysregulation in T2DM can be linked to dysfunction within their mitochondria.Declaration of funding: EPSRC....

Replacement with mono-unsaturated fatty acids (MUFA) or poly-unsaturated fatty acids (PUFA) reduces inflammation in the pre-diabetic subjects but the benefits are unclear in subjects with type 2 diabetes mellitus (T2DM). Our aim was to investigate whether saturated fatty acids (SFA), MUFA and PUFA produce a similar adipocyte inflammatory response, which may explain the rationale for maintained systemic inflammation noted in subjects with T2DM. The differentiated human preadipo...

Background: Adipose tissue (AT) may have a significant role in obesity associated inflammation but, the mechanisms underlying the pathogenesis of obesity induced inflammation remains unclear. Recent murine studies indicate that ER stress is critical to the initiation and integration of inflammation and insulin signalling pathways. The ER stress occurs primarily due to accumulation of unfolded proteins and results in activation of the unfolded protein response to restore ER hom...

Background: Metabolic endotoxaemia (raised bacterial endotoxin in serum after high-fat feeding) has been shown to reduce insulin sensitivity in humans through systemic inflammation and oxidative stress. Mitochondria represent the main source of cellular reactive oxygen species and mutations in mitochondrial DNA often result in a diabetic phenotype. However, the direct cellular impact of endotoxin on mitochondrial respiration and DNA integrity, particularly within the context o...