Hyperhomocysteinemia and Low Folate and Vitamin B12 Are Associated with Vascular Dysfunction and Impaired Nitric Oxide Sensitivity in Morbidly Obese Patients.

Mohamed Haloul,Mohammed Imaduddin Mirza,Shane A Phillips,Mohamed M Ali,Patrice Frederick,Abeer M Mahmoud,Giulianotti P Cristoforo,Smita Jagdish Vinjamuri,Maryam Qureshi,Dina Naquiallah,Antonio Gangemi,Mario Masrur,Francesco M Bianco,Chandra Hassan

doi:10.3390/nu12072014

Mohamed Haloul, Mohammed Imaduddin Mirza + Show 12 more

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https://doi.org/10.3390/nu12072014

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Abstract

There is a high prevalence of hyperhomocysteinemia that has been linked to high cardiovascular risk in obese individuals and could be attributed to poor nutritional status of folate and vitamin B12. We sought to examine the association between blood homocysteine (Hcy) folate, and vitamin B12 levels and vascular dysfunction in morbidly obese adults using novel ex vivo flow-induced dilation (FID) measurements of isolated adipose tissue arterioles. Brachial artery flow-mediated dilation (FMD) was also measured. Subcutaneous and visceral adipose tissue biopsies were obtained from morbidly obese individuals and non-obese controls. Resistance arterioles were isolated in which FID, acetylcholine-induced dilation (AChID), and nitric oxide (NO) production were measured in the absence or presence of the NO synthase inhibitor, L-NAME, Hcy, or the superoxide dismutase mimetic, TEMPOL. Our results demonstrated that plasma Hcy concentrations were significantly higher, while folate, vitamin B12, and NO were significantly lower in obese subjects compared to controls. Hcy concentrations correlated positively with BMI, fat %, and insulin levels but not with folate or vitamin B12. Brachial and arteriolar vasodilation were lower in obese subjects, positively correlated with folate and vitamin B12, and inversely correlated with Hcy. Arteriolar NO measurements and sensitivity to L-NAME were lower in obese subjects compared to controls. Finally, Hcy incubation reduced arteriolar FID and NO sensitivity, an effect that was abolished by TEMPOL. In conclusion, these data suggest that high concentrations of plasma Hcy and low concentrations of folate and vitamin B12 could be independent predictors of vascular dysfunction in morbidly obese individuals.

Highlights

Obesity is a major public health concern that affects more than one-third of the population and increases the risk of other health problems, including metabolic and cardiovascular diseases [1].Several factors contribute to the increasing trend in obesity, including genetic predisposition and lack of physical activity, yet the most predominant factor is excess caloric intake
The average fasting blood glucose and HbAlc were not statistically different between the two groups, the average fasting plasma insulin and HOMA-IR were lower in the control group compared to obese subjects by
low-density lipoproteins (LDL), and triglycerides did not differ between the groups; the average high-density lipoproteins (HDL) level was 30% higher (p = 0.0004) in the non-obese compared to obese subjects

Summary

Introduction

Obesity is a major public health concern that affects more than one-third of the population and increases the risk of other health problems, including metabolic and cardiovascular diseases [1].Several factors contribute to the increasing trend in obesity, including genetic predisposition and lack of physical activity, yet the most predominant factor is excess caloric intake. Obese individuals have a relatively high incidence of micronutrient deficiencies [2] Some of these micronutrients act as cofactors in critical biological pathways in the body, such as energy metabolism and immune function. The final product, 5-methyl THF, donates its methyl group to homocysteine (Hcy) to produce methionine, which is critical for the formation of the ultimate methyl donor, S-Adenosylmethionine (SAM). The latter is metabolized to S-adenosylhomocysteine (SAH), which could be reversibly converted to Hcy via the enzyme SAH hydrolase. The fate of Hcy is through re-methylation to methionine via the folate-dependent pathway or transsulfuration to cystathionine, via cystathionine β-synthase [3]

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