Searchable abstracts of presentations at key conferences in endocrinology

ea0065p184 | Metabolism and Obesity | SFEBES2019

Vitamin B12 deficiency leads to fatty acid metabolism dysregulation and increased pro-inflammatory cytokine production in human adipocytes and in maternal subcutaneous and omental adipose tissue

Samavat Jinous , Adaikalakoteswari Antonysunil , Boachie Joseph , Jackisch Laura , McTernan Philip , Christian Mark , Saravanan Ponnusamy

Vitamin B12 (B12) is an essential micronutrient required for several metabolic reactions. Animal and clinical studies show that B12-deficiency is associated with metabolic syndrome. Given the key metabolic role of adipose tissue, we investigated whether B12 deficiency may affect triglyceride synthesis and lipid metabolism leading to adipose tissue inflammation. The AbdSc pre-adipocyte cell line (Chub-S7) and human AbdSc primary pre-adipocytes were differentiated under differen...

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 & 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...

ea0038p209 | Obesity, diabetes, metabolism and cardiovascular | SFEBES2015

Vitamin B12 deficiency alters adipogenesis and associated microRNA’s in human adipocytes

Adaikalakoteswari Antonysunil , Vatish Manu , McTernan Philip , Randeva Harpal , Tripathi Gyanendra , Saravanan Ponnusamy

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...

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), ╬▓Klotho ...

ea0031p201 | Obesity, diabetes, metabolism and cardiovascular | SFEBES2013

Unfolded protein response pathway, IRE1α-XBP1 is altered during adipogenesis in obese human adipocytes

Voyias Philip , McCarthy Ciara , Antonysunil Adaikala , Kumsaiyai Warunee , Harte Alison , McTernan Philip , Tripathi Gyanendra

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, IRE1╬▒-XBP1 regulates hepatic lipogenesis and the role of this pathway in adipogenesis in murine adipocytes has also been confirmed. Our tea...

ea0031p204 | Obesity, diabetes, metabolism and cardiovascular | SFEBES2013

Altered mitochondrial dynamics in obesity: redressing the balance through bariatric surgery?

McCarthy Ciara , Voyias Philip , Antonysunil Adaikala , Harte Alison , Saravanan Ponnusamy , Kyrou Ioannis , Tripathi Gyanendra , McTernan Philip

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....

ea0028p213 | Obesity, diabetes, metabolism and cardiovascular | SFEBES2012

Chronic or intermittent exposure to Oleic acid (MUFA) induces a greater NFκB activated inflammatory response than Eicosapentaenoic acid (PUFA) in differentiated human adipocytes

Piya Milan , Harte Alison , McGee Kirsty , Reddy Narendra , Tripathi Gyanendra , McTernan Philip , Kumar Sudhesh

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...

ea0021p137 | Diabetes and metabolism | SFEBES2009

Salicylate induces insulin sensitivity by alleviating endoplasmic reticulum (ER) stress in cultured primary human adipocytes

Tripathi Gyanendra , Alhusaini Saif , McGee Kirsty , Lois Kostantinos , Harte Alison , McTernan Philip , Kumar Sudhesh

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...