Searchable abstracts of presentations at key conferences in endocrinology

ea0086p220 | Metabolism, Obesity and Diabetes | SFEBES2022

Endotoxin Impairs Brown Fat Phenotype and Mitochondrial Function in 2D and 3D Brown Adipocytes Models

Omran Farah , Murphy Alice , McTernan Philip G , Christian Mark

Background: Dysfunctional adipose tissue in obesity is known to contribute to metabolic diseases, including type 2 diabetes mellitus (T2DM). This may be due to increased gut-derived endotoxemia (LPS) reducing brown adipose tissue (BAT) activity and altering mitochondrial function. However, the effect of LPS on BAT activity in 3D culture models has not been studied, despite giving a better representation of in-vivo tissue. Therefore, this study investigated the effects of LPS o...

ea0065p185 | Metabolism and Obesity | SFEBES2019

Endotoxin and adiposity as mediators of down-regulating the BRITE fat phenotype

Omran Farah , Murphy Alice , Jackisch Laura , Samavat Jinus , McTernan Philip G , Christian Mark

Background: The acquisition of brown-adipocyte-properties by white-adipocytes (BRITE-adipocytes) is an appealing-prospect to combat obesity and type-2-diabetes-Mellitus (T2DM). This may support counteracting the impact of inflammation and mitochondrial-dysfunction, which contribute to the obesity-pathogenesis. However, our previous-finding shave shown that the gut-derived-inflammatory-agent endotoxin can increase the inflammatory-response in white-adipose-tissue impacted by ob...

ea0059p168 | Obesity & metabolism | SFEBES2018

The impact of freeze dried broccoli extract to mitigate inflammation in human adipocytes through the mevalonate pathway

Murphy Alice , Azharian Sahar , Tripathi Gyanendra , Barker Guy , Chappell Michael , McTernan Philip G

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...

ea0031p179 | Obesity, diabetes, metabolism and cardiovascular | SFEBES2013

FGF21 action on human adipose tissue compromised by reduced βKlotho and FGFR1 expression in type 2 diabetes mellitus

Piya Milan K , Harte Alison L , Chittari Madhu V , Tripathi Gyanendra , Kumar Sudhesh , McTernan Philip G

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 ...

ea0077p50 | Metabolism, Obesity and Diabetes | SFEBES2021

Lipocalin 2, a mediator or marker of adipocyte dysfunction?

Parenti Cristina , Lad Nikita , Williams C Neil , Sharpe Graham R , Nelson Carl P , Murphy Alice M , McTernan Philip G

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...

ea0077p176 | Metabolism, Obesity and Diabetes | SFEBES2021

Asprosin impact on mitochondrial metabolism in obese adipose tissue, a tale of two depots?

Lad Nikita , Murphy Alice M , Parenti Cristina , Nelson Carl P. , Williams Neil C. , Sharpe Graham R. , McTernan Philip G.

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...

ea0086p69 | Metabolism, Obesity and Diabetes | SFEBES2022

The effect of novel adipokine asprosin on mitochondrial function in human airway epithelial cells

Lad Nikita , Murphy Alice M , Parenti Cristina , Williams Neil C , Nelson Carl P , Sharpe Graham R , McTernan Philip G

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...

ea0044p179 | Obesity and Metabolism | SFEBES2016

Metabolic endotoxaemia impairs mitochondrial respiration and insulin sensitivity in human adipocytes

de la Escalera Lucia Martinez , Jackisch Laura , Murphy Alice , Piya Milan , Kumar Sudhesh , Tripathi Gyanendra , McTernan Philip G

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...

ea0031p13 | Bone | SFEBES2013

Identification of a novel heterozygous mutation in exon 50 of the COL1A1 gene manifesting clinically as osteogenesis imperfecta

Owen Nina , Reddy Narendra , Aftab Saboor AS , Harte Alison L , McTernan Philip G , Tripathi Gyanendra , Barber Thomas M

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...

ea0031p205 | Obesity, diabetes, metabolism and cardiovascular | SFEBES2013

Irisin as a central regulator in energy homeostasis?

Piya Milan K , Harte Alison L , Sukumar Kavitha , James Sean , Tripathi Gyanendra , Kumar Sudhesh , Vatish Manu , McTernan Philip G

Background/objectives: Irisin is a novel myokine, released predominantly by skeletal muscle. Peripheral action of irisin improves glucose homeostasis, increases energy expenditure and induces browning of adipocytes, with therapeutic potential for use in weight loss. However, there are no human studies on the central role of irisin in the regulation of appetite or energy expenditure. This study sought to examine the potential central role of irisin, by demonstrating irisin in h...