Obesity is a worldwide epidemic responsible for 5% of global mortality. The risks of developing other key metabolic disorders like diabetes, hypertension and cardiovascular diseases (CVDs) are increased by obesity, causing a great public health concern. A series of epidemiological studies and animal models have demonstrated a relationship between the importance of vitamin B12 (B12) and various components of metabolic syndrome. High prevalence of low B12 levels has been shown in European (27%) and South Indian (32%) patients with type 2 diabetes (T2D). A longitudinal prospective study in pregnant women has shown that low B12 status could independently predict the development of T2D five years after delivery. Likewise, children born to mothers with low B12 levels may have excess fat accumulation which in turn can result in higher insulin resistance and risk of T2D and/or CVD in adulthood. However, the independent role of B12 on lipid metabolism, a key risk factor for cardiometabolic disorders, has not been explored to a larger extent. In this review, we provide evidence from pre-clinical and clinical studies on the role of low B12 status on lipid metabolism and insights on the possible epigenetic mechanisms including DNA methylation, micro-RNA and histone modifications. Although, there are only a few association studies of B12 on epigenetic mechanisms, novel approaches to understand the functional changes caused by these epigenetic markers are warranted.

Introduction: The human immunodeficiency virus (HIV) and malaria destroy important cells required for proper immunological and haematological functioning of the body. This research therefore aimed to assess the effect of malaria on CD4+ and haemoglobin (Hb) levels of HIV-malaria co-infected patients. Methodology: The study was performed by sampling 220 adult HIV patients on highly active anti retroviral therapy (HAART) who routinely visited the Tema General Hospital in Ghana. Blood samples were obtained for both blood film microscopy identification of malaria parasites and analysis using rapid diagnostic test kits. A BD Facscount Analyzer was used in the quantification of CD4+ levels. Results: Of the 220 patients sampled, 34 (15.5%) were HIV-malaria co-infected, all of whom (34; 100%) had CD4+ counts below the normal range, while 23 (12.9%) of the HIV mono-infected patients had normal CD4+ counts. Almost all HIV-malaria co-infected patients (33; 97.1%) had low Hb levels, whereas 79 (42.5%) of the HIV mono-infected patients had normal Hb. Malaria infection strongly correlated positively and significantly with both low CD4+ count (χ2 = 0.828, P = 0.003) and Hb (χ2 = 0.817, P = 0.004) levels. Conclusion: Malaria co-infection with HIV decreases CD4+ T cells and Hb levels in patients. It is therefore recommended that HIV patients in malaria endemic areas should adhere to malaria preventive measures.

Background/Aims: Rise in global incidence of obesity impacts metabolic health. Evidence from human and animal models show association of vitamin B12 (B12) deficiency with elevated BMI and lipids. Human adipocytes demonstrated dysregulation of lipogenesis by low B12 via hypomethylation and altered microRNAs. It is known de novo hepatic lipogenesis plays a key role towards dyslipidaemia, however, whether low B12 affects hepatic metabolism of lipids is not explored. Methods: HepG2 was cultured in B12-deficient EMEM medium and seeded in different B12 media: 500nM(control), 1000pM(1nM), 100pM and 25pM(low) B12. Lipid droplets were examined by Oil Red O (ORO) staining using microscopy and then quantified by elution assay. Gene expression were assessed with real-time quantitative polymerase chain reaction (qRT-PCR) and intracellular triglycerides were quantified using commercial kit (Abcam, UK) and radiochemical assay. Fatty acid composition was measured by gas chromatography and mitochondrial function by seahorse XF24 flux assay. Results: HepG2 cells in low B12 had more lipid droplets that were intensely stained with ORO compared with control. The total intracellular triglyceride and incorporation of radio-labelled-fatty acid in triglyceride synthesis were increased. Expression of genes regulating fatty acid, triglyceride and cholesterol biosynthesis were upregulated. Absolute concentrations of total fatty acids, saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), trans-fatty acids and individual even-chain and odd-chain fatty acids were significantly increased. Also, low B12 impaired fatty acid oxidation and mitochondrial functional integrity in HepG2 compared with control. Conclusion: Our data provide novel evidence that low B12 increases fatty acid synthesis and levels of individual fatty acids, and decreases fatty acid oxidation and mitochondrial respiration, thus resulting in dysregulation of lipid metabolism in HepG2. This highlights the potential significance of de novo lipogenesis and warrants possible epigenetic mechanisms of low B12.

The liver mass constitutes hepatocytes expressing receptors for vitamin B12 (B12)-bound transporters in circulation. However, intrahepatic and circulating B12 interrelationship levels remain unclear. We assessed the intracellular B12 levels at various circulating B12 concentrations in human HepG2 cell-line and liver tissue levels of B12 in the C57BL/6 mouse model. In HepG2 cells treated with a range of B12 concentrations, the intracellular and circulatory B12 levels, transcript and protein levels of B12 receptor (CD320) and transporter (TCN2) were determined using immunoassays, qRT-PCR and Western blot, respectively. Similar assessments were done in plasma and liver tissue of C57BL/6 mice, previously fed a diet of either a high or low B12 (30.82 µg B12/kg and 7.49 µg B12/kg, respectively) for 8–10 weeks. The physiological B12 status (0.15–1 nM) resulted in increased levels of intracellular B12 in HepG2 cells compared to supraphysiological levels of B12 (>1 nM). Gene and protein expression of CD320 and TCN2 were also higher at physiological levels of B12. Progressively increasing extracellular B12 to supraphysiological levels led to relative decreased levels of intracellular B12, lower expression of gene and protein levels of CD320 and TCN2. Similar results were observed in liver tissue from mice fed on a low B12 diet verses high B12 diet. These findings suggest that unlike supraphysiological B12, physiological levels of B12 in the extracellular media or circulation accelerates active transport of B12, and expression of CD320 and TCN2, resulting in higher relative uptake of B12 in hepatocytes.

Background: Anaemia persistently remains a grave public health challenge in most sub-Saharan African countries. Understanding the perspectives of young adults concerning the multi-factorial nature of anaemia may be an important step towards meeting the 2025 global nutrition target of halving anaemia since these individuals might be in the process of reproductive decisions. Aim: To explore the relationship between students’ knowledge about individuals at risk of developing anaemia, and anaemia consequences, and anaemia prevention strategies in a tertiary student cohort. Methods: This sequential exploratory study adopted a mixed-methods approach to triangulate the data collection. A semi-structured questionnaire was used to gather baseline data regarding students’ perspective on anaemia. Themes that emerged from the initial questionnaire data analyses guided a focus group discussion (FGD) to further explore students’ perspectives on anaemia. FGD data was thematically analysed to unearth reasons behind questionnaire item selection. Structural equation modeling (SEM) was used to explore the relationship between constructs in the anaemia knowledge questionnaire. Results: Overall, 543 students participated in the initial questionnaire data acquisition compared to 16 in the FGD. Our latent variable structural model showed that knowing the causes of anaemia did not significantly (p > 0.05) associate with either knowledge about anaemia consequences (b = 0.113) or knowledge about anaemia prevention strategies (b = 0.042). However, knowledge about individuals at-risk of anaemia was significantly positively associated with both anaemia prevention strategies (b = 0.306, p < 0.05) and knowledge about consequences of anaemia (b = 0.543, 95%). Moreover, knowing the consequences of anaemia seemed to significantly positively mediate the association between knowledge about at-risk groups and preventive measures that could be adopted (b = 0.410, p < 0.05). Conclusions: Systems thinking public health educational campaigns that highlight the consequences of anaemia and at-risk groups are more likely to inspire the adoption of preventive strategies among young adults.

Background: Prolonged metformin treatment decreases vitamin B12 (B12) levels, whereas low B12 is associated with dyslipidaemia. Some studies have reported that metformin has no effect on intrahepatic triglyceride (TG) levels. Although AMP-activated protein kinase (AMPK) activation via adiponectin lowers hepatic TG content, its role in B12 deficiency and metformin has not been explored. We investigated whether low B12 impairs the beneficial effect of metformin on hepatic lipid metabolism via the AMPK-adiponectin axis. Methods: HepG2 was cultured using custom-made B12-deficient Eagle’s Minimal Essential Medium (EMEM) in different B12-medium concentrations, followed by a 24-h metformin/adiponectin treatment. Gene and protein expressions and total intracellular TG were measured, and radiochemical analysis of TG synthesis and seahorse mitochondria stress assay were undertaken. Results: With low B12, total intracellular TG and synthesized radiolabelled TG were increased. Regulators of lipogenesis, cholesterol and genes regulating fatty acids (FAs; TG; and cholesterol biosynthesis were increased. FA oxidation (FAO) and mitochondrial function were decreased, with decreased pAMPKα and pACC levels. Following metformin treatment in hepatocytes with low B12, the gene and protein expression of the above targets were not alleviated. However, in the presence of adiponectin, intrahepatic lipid levels with low B12 decreased via upregulated pAMPKα and pACC levels. Again, combined adiponectin and metformin treatment ameliorated the low B12 effect and resulted in increased pAMPKα and pACC, with a subsequent reduction in lipogenesis, increased FAO and mitochondrion function. Conclusions: Adiponectin co-administration with metformin induced a higher intrahepatic lipid-lowering effect. Overall, we emphasize the potential therapeutic implications for hepatic AMPK activation via adiponectin for a clinical condition associated with B12 deficiency and metformin treatment.