Endocrine Abstracts

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...

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...

Background: Low vitamin B12 (B12) during pregnancy is associated with higher maternal obesity, insulin resistance (IR) and gestational diabetes (GDM). However, it is not clear whether these are causally related.Objective: B12 is a key co-factor of the DNA methylation cycle (1-carbon metabolism). We hypothesize that B12 plays a role in epigenetic regulation by altering circulating miRNAs (miRs) during adipocyte differentiation...

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...

Background: Low vitamin B12 (B12) during pregnancy is associated with higher maternal obesity, insulin resistance (IR) and gestational diabetes (GDM). However, it is not clear whether these are causally related.Objective: B12 is a key co-factor of the DNA methylation cycle (1-carbon metabolism). We hypothesize that B12 plays a role in epigenetic regulation by altering circulating miRNAs (miRs) during adipocyte differentiation...

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...

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...

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...

Adipose tissue (AT) plays a central role in integrating energy metabolism and glucose homeostasis. It is the major site of fatty acid storage as triglycerides and is body’s largest cholesterol pool. In AT cholesterol is mostly found in its free, non-esterified form. There is accumulating evidence that cholesterol imbalance in AT is closely associated with adipocyte dysfunction and obesity-mediated metabolic complications, including low levels of high-density lipoprotein c...

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, IRE1α-XBP1 regulates hepatic lipogenesis and the role of this pathway in adipogenesis in murine adipocytes has also been confirmed. Our tea...