Endocrine Abstracts

We have previously shown that the orexigenic hormone NPY is secreted by human adipocytes. The orexigenic hormone NPY(1–36) is truncated by the dipeptidyl-inhibitor IV (DPP-IV) to NPY(3–36) as consequence its affinity changes from receptor Y1 to Y4 and 5. The aim was to investigate whether DPP-IV is expressed in adipose tissue (AT) where it could modulate adipose tissue growth through modulation of NPY activity. This is relevant in light of DPP-IV inhibitors utilised ...

Background: Lipocalin 2 (NGAL) is considered a pro-inflammatory adipokine. Noting the conflicting reports as to the role of Lipocalin 2 in metabolic disease, it remains unclear whether an acute or chronic state affects its impact on adipocyte function. In an attempt to address this our current studies investigated for the first time in humans, whether Lipocalin 2 in abdominal subcutaneous adipose tissue (AT) may influence mitochondrial function and browning of adipocytes, as c...

Background: In an obese state, pro-inflammatory adipokines can lead to mitochondrial dysfunction and reduced brown adipocytes properties in white adipocytes (BRITE adipocytes), all of which contribute to the pathogenesis of obesity and type 2 diabetes mellitus (T2DM). A recent novel adipokine, asprosin, that influences appetite and glucose homeostasis, appears to drive inflammation in obesity. However, asprosin expression in human adipose tissue (AT) depots, its impact on mito...

Background: Asprosin is a novel adipokine involved in appetite and glucose regulation. During obesity, circulating asprosin is increased, which leads to increased inflammation and can disrupt cellular functions such as mitochondrial respiration. Asthma is a comorbidity of obesity, with both diseases sharing an inflammatory profile and mitochondrial dysfunction. This study investigated the molecular links between asthma and obesity, by exploring whether asprosin causes mitochon...

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...

Background: The pathogenesis of obesity and T2DM mediates mitochondrial dysfunction which, in part, may arise as a consequence of endoplasmic reticulum (ER) stress. However, the potential impact of ER stress on mitochondria dysfunction is unclear. Therefore, we investigated whether induction of ER stress contributes to mitochondrial dysfunction in human adipocytes using 1) human differentiated adipocyte cell line (Chub-S7, n=12); and 2) primary differentiated lean and...

Background and aims: Current evidence highlights that dietary cholesterol, trans-fatty acids and saturated fatty acids (SFAs) are all known to increase the levels of systemic atherogenic lipoproteins and cardiovascular disease. The aim of this study was to observe the direct effect of dietary change, via a calorie-restricted diet on i) cardio-metabolic profile and ii) a high-fat meal challenge pre- and post-3-month intervention.Methods: T2DM subjects (Sa...

Background: Small frequent meals are often recommended for weight loss, with supporting evidence often provided from studies in diabetes. Dietary meal content is also relevant, as high fat meals cause systemic inflammation via gut derived bacteria, endotoxin. As such, repeated meals may exacerbate this. In contrast, dietary induced thermogenesis, related to meal size, may reduce with small frequent meals.Aim: Therefore, the aim of this study was to compa...

Background: Vitamin B12 (B12) insufficiency is common in pregnancy and independently predicts insulin resistance (IR) in the offspring. B12 is an important key nutrient for epigenetic programming through regulating DNA methylation. Such B12 DNA methylation may influence leptin, a strong candidate for methylation, which could impact both insulin resistance (IR) and associated neonatal metabolic risk. Therefore, we hypothesize that leptin can be programmed by maternal B12 which ...

Introduction: Osteogenesis imperfecta (OI) is a rare, heterogeneous, genetic connective tissue disorder that manifests clinically as bone fragility, brittleness and growth disorder. Effective diagnosis is important (although often challenging) to enable institution of early and effective multidisciplinary management.The case: A 19-year-old woman was referred to the Endocrine clinic at the Warwickshire Institute for the Study of Diabetes, Endocrinology an...