Searchable abstracts of presentations at key conferences in endocrinology

ea0050p204 | Diabetes and Cardiovascular | SFEBES2017

Effect of vitamin B12 deficiency on the lipid lowering effect of metformin in the liver

Boachie Joseph , Adaikalakoteswari Antonysunil , Samavat Jinus , Saravanan Ponnusamy

Background: Metformin is currently the first drug of choice for treatment of type 2 diabetes (T2D). Metformin is known to reduce lipid levels through activation of AMP activated protein kinase-alpha (AMPKα). Metformin induces deficiency of vitamin B12 (B12) in patients with T2D. In humans, studies have shown that low B12 is associated with dyslipidemia (higher triglycerides and low HDL). Therefore, we investigated whether B12 deficiency m...

ea0050p204 | Diabetes and Cardiovascular | SFEBES2017

Effect of vitamin B12 deficiency on the lipid lowering effect of metformin in the liver

Boachie Joseph , Adaikalakoteswari Antonysunil , Samavat Jinus , Saravanan Ponnusamy

Background: Metformin is currently the first drug of choice for treatment of type 2 diabetes (T2D). Metformin is known to reduce lipid levels through activation of AMP activated protein kinase-alpha (AMPKα). Metformin induces deficiency of vitamin B12 (B12) in patients with T2D. In humans, studies have shown that low B12 is associated with dyslipidemia (higher triglycerides and low HDL). Therefore, we investigated whether B12 deficiency m...

ea0065p187 | Metabolism and Obesity | SFEBES2019

Low B12 is associated with increased de novo synthesis of ‘unsafe’ fatty acids in the liver

Boachie Joseph , Adaikalakoteswari Antonysunil , Samavat Jinus , Saravanan Ponnusamy

Background: Vitamin B12 (B12) deficiency is associated with obesity and was recently shown to trigger lipid accumulation in the adipose tissues and liver. The body is capable of synthesizing fatty acids (FAs) endogenously via de novo lipogenesis in the liver. However, dysregulated levels are associated with adverse consequences in subjects. We therefore assessed B12 regulation of de novo fatty acid synthesis and the profile of various FAs in hepatocytes.<...

ea0059p161 | Obesity &amp; metabolism | SFEBES2018

B12 Receptors and transporters regulate the uptake and storage of vitamin B12 in hepatocytes

Boachie Joseph , Adaikalakoteswari Antonysunil , Samavat Jinus , Ilona Goljan , Saravanan Ponnusamy

Background: The liver stores 10 μg cobalamin per gram protein and able to hold 50% (1–1.5 mg) of body’s B12. Making up the bulk of the liver, hepatocytes express receptors regulating cellular uptake of B12 in the liver. However, relationship between circulating and intracellular B12 levels as well as regulation of hepatic uptake of B12 is unexplored.Objective: To assess the regulation of cellular uptake and storage of B12 in hepatocytes in...

ea0059p163 | Obesity &amp; metabolism | SFEBES2018

Metformin treatment fails to restore fatty acid oxidation in low vitamin B12 hepatocytes

Boachie Joseph , Antonysunil Adaikalakoteswari , Samavat Jinus , Saravanan Ponnusamy

Background: Metformin is utilized in clinical trials for treatment of non-alcoholic fatty liver disease (NAFLD) and obesity. Metformin increases AMP:ATP ratio activating AMP activated protein kinase-alpha (AMPKα), a mediator of fatty acid oxidation (FAO) in the liver. Meanwhile, prolonged oral metformin therapy in T2DM decreases vitamin B12(B12) in patients and evidence shows that low B12 dysregulates lipid levels. We therefore investigated whether low B12 impairs FAO ind...

ea0050p326 | Obesity and Metabolism | SFEBES2017

Low vitamin B12 induces de novo lipogenesis in human hepatocytes

Boachie Joseph , Adaikalakoteswari Antonysunil , Samavat Jinus , Zammit Victor , Irshad Zehra , Saravanan Ponnusamy

Background: Vitamin B12 (B12) deficiency results in disturbance of 1-carbon metabolites [methylmalonyl coenzyme A (MMA), homocysteine and S-adenosyl homocysteine (SAH), S-adenosyl methionine (SAM) and methionine] that collectively affect lipogenesis leading to risk of cardiovascular diseases. In clinical studies, B12 deficiency is associated with higher BMI and dyslipidaemia (high triglycerides and low HDL). The role of B12 in hepatic metabolism of...

ea0050p326 | Obesity and Metabolism | SFEBES2017

Low vitamin B12 induces de novo lipogenesis in human hepatocytes

Boachie Joseph , Adaikalakoteswari Antonysunil , Samavat Jinus , Zammit Victor , Irshad Zehra , Saravanan Ponnusamy

Background: Vitamin B12 (B12) deficiency results in disturbance of 1-carbon metabolites [methylmalonyl coenzyme A (MMA), homocysteine and S-adenosyl homocysteine (SAH), S-adenosyl methionine (SAM) and methionine] that collectively affect lipogenesis leading to risk of cardiovascular diseases. In clinical studies, B12 deficiency is associated with higher BMI and dyslipidaemia (high triglycerides and low HDL). The role of B12 in hepatic metabolism of...

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...