Endocrine Abstracts

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...

Gestational diabetes mellitus (GDM) increases fetal morbidity/mortality, and is associated with elevated risks of offspring cardiometabolic disease. These risks are compounded in infants born large for gestational age (LGA) rather than appropriate size (AGA), a common complication of GDM associated with altered placental function. Circulating extracellular vesicle (EV)-associated miRNAs are internalised into the placenta and are emerging as key GDM mediators, with their role i...

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...

Gestational diabetes (GDM) is a form of diabetes that is first diagnosed during pregnancy, complicating 8–24% of all pregnancies. Despite treatment, substantial numbers of babies are born large for gestational age (LGA), predisposing them to cardio-metabolic disease in adulthood. It is difficult to predict which pregnancies are most at risk. The study aimed to determine if circulating maternal serum small extracellular vesicle (sEV) miRNAs have the potential to predict al...

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...

Background: Macrosomia (BW >4.5 kg) is a well-recognised complication of maternal hyperglycaemia and is associated with poor maternal and foetal outcomes. Traditional risk factors of macrosomia do not fully explain all variation as it can happen in normoglycaemia and in well-controlled diabetes. The relative contributions of these factors in different ethnicities are unknown. We investigated the predictors of BW in South Asian (SA) and White Caucasian (WC) pregnancies, and...

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...

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....

Background: Maternal B12 deficiency is linked with adverse metabolic disorders in infants. B12 has a potential epigenetic role which could influence placental dysfunction and fetal metabolism. Adipokines such as leptin and adiponectin play a major role in placental development by regulating lipid metabolism. Alterations in in-utero programming develop risk to obesity and metabolic diseases in offspring. B12 deficiency in mothers has been linked with higher cor...