Searchable abstracts of presentations at key conferences in endocrinology

ea0077p71 | Metabolism, Obesity and Diabetes | SFEBES2021

Lipopolysaccharide signalling modulates brown fat transcriptome and cytokine secretion

Omran Farah , Murphy Alice , McTernan Philip , Christian Mar

Background: Brown adipose tissue (BAT) thermogenesis offers an appealing prospect to combat obesity. Obesity is characterised by a state of chronic inflammation in adipose tissue mediated by the secretion of a range of inflammatory-cytokines. Our previous work has highlighted that a gut-derived inflammatory agent, lipopolysaccharide (LPS), reduces brown adipocyte activity, insulin sensitivity and mitochondrial-function and is increased with obesity and type 2 diabetes mellitus...

ea0077p183 | Metabolism, Obesity and Diabetes | SFEBES2021

The influence of metabolic states and a high fat meal on circulating chemerin

Murphy Alice , Dumbell Rebecca , Varma Madhu , Helfer Gisela , McTernan Philip

Background: Chemerin is a multifunctional adipokine involved in pathogenesis of metabolic disease by regulating inflammation, adipocyte plasticity and glucose metabolism. It is known to be influenced by age, adiposity and triglycerides, and supports important roles in systemic lipid and glucose metabolism.However, the direct acute effects of circulating chemerin on varying metabolic disease states given a high–saturated fat meal has not been addressed.<p clas...

ea0086p54 | Metabolism, Obesity and Diabetes | SFEBES2022

Metabolic Endotoxemia impacts mitochondrial function and adipocyte browning in a depot specific manner in Human abdominal adipose tissue

Murphy Alice , Omran Farah , Piya Milan , Christian Mark , McTernan Philip

Introduction: Central obesity is a significant risk factor for type 2 diabetes mellitus (T2DM), with omental adipose tissue (AT) particularly involved in such risk. Additionally, obesity can cause low-level gut-derived endotoxemia, which may drive metabolic dysfunction in AT through mitochondrial damage and reduced BRITE (brown-in-white) adipocytes. Bariatric surgery reduces obesity and may prevent such dysfunction. This study investigated whether endotoxin: 1) impairs mitocho...

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...

ea0065p202 | Metabolism and Obesity | SFEBES2019

Endoplasmic reticulum stress directly impacts mitochondrial function in human adipocytes

Jackisch Laura , Murphy Alice , Kumar Sudhesh , Randeva Harpal , Tripathi Gyanendra , McTernan Philip

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...

ea0059p168 | Obesity &amp; 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...

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...

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...