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.

We thank the editor and the reviewers for their thoughtful review of our manuscript and for the opportunity to improve and resubmit. The detailed comments the authors received are indeed beneficial and improve the quality of our data presentation and interpretation. We have responded to the reviewers' comments/critiques below and have incorporated the recommended changes in the manuscript. Major concernsComment # 1: Do you have information on dietary preferences in your sample? Are there omnivores, vegetarian or vegans? This is important due to the potential use of vitamin supplements with vitamin B12. The authors did not discuss the differences in folate and vitamin B12 between controls and subjects with obesity, and how this is related with the observed methylation patterns… this should be addressed due to its one of the strengths of this study. Response to comment # 1:We agree with the reviewer and we obtained questionnaires about supplementations however, most subjects were not able to recall taking supplements that specifically rich in folate or vitamin B12. Accordingly, we decided to measure actual concentrations of folate and B12 in plasma. Also, we do not have specific information about dietary preferences of our subjects but realizing the importance of this information, we will start to implement this questionnaire in our future studies. We also agree that the part about vitamin B12 and folate in obese and non-obese subjects and the relation to methylation was missing in the discussion. Per your recommendation, we added a new paragraph that discusses this part (lines 341-360).Comment # 2: The data in table 2 was analyzed by sex? Considering that HDL-C cut-off is different among men and women…Response to comment # 2: Results for HDL-C did not show significant differences between males and females within each group (obese and non-obese). When compared, the p value was higher than 0.7 in both groups. Comment # 3:The authors show interesting data in Table 2, where HOMA index and FPI is higher in obese subjects in comparison to controls, however, FPG and HbA1c are not different among groups as expected. Please discuss about these result.Response to comment # 3: Insulin can be higher in obese individuals which results in higher HOMA-IR at earlier stages of insulin resistance before the conditions mature to full-blown diabetes where glucose metabolism is actually compromised and manifested as high blood glucose. We believe that some of subjects in the obese group are at early stages of insulin resistance but since they are young (mid 30s in average), a complete picture of diabetes might not have been developed yet. A statement that explain this was added to the discussion (lines 260-263)Comment # 4: Alcohol consumption was measured by a questionnaire, is this validated? This information is not described in methods, fix this issue. In table 2 the data appears as "alcohol drinkers %", however, in the discussion, the authors mentioned that they have classified into none, mild, moderate and heavy drinking, but this...

There is a high prevalence of vitamin-D deficiency in obese individuals that could be attributed to vitamin-D sequestration in the adipose tissue. Associations between vitamin-D deficiency and unfavorable cardiometabolic outcomes were reported. However, the pathophysiological mechanisms behind these associations are yet to be established. In our previous studies, we demonstrated microvascular dysfunction in obese adults that was associated with reduced nitric oxide (NO) production. Herein, we examined the role of vitamin D in mitigating microvascular function in morbidly obese adults before and after weight loss surgery. We obtained subcutaneous (SAT) and visceral adipose tissue (VAT) biopsies from bariatric patients at the time of surgery (n = 15) and gluteal SAT samples three months post-surgery (n = 8). Flow-induced dilation (FID) and acetylcholine-induced dilation (AChID) and NO production were measured in the AT-isolated arterioles ± NO synthase inhibitor N(ω)-nitro-L-arginine methyl ester (L-NAME), hydrogen peroxide (H2O2) inhibitor, polyethylene glycol-modified catalase (PEG-CAT), or 1,25-dihydroxyvitamin D. Vitamin D improved FID, AChID, and NO production in AT-isolated arterioles at time of surgery; these effects were abolished by L-NAME but not by PEG-CAT. Vitamin-D-mediated improvements were of a higher magnitude in VAT compared to SAT arterioles. After surgery, significant improvements in FID, AChID, NO production, and NO sensitivity were observed. Vitamin-D-induced changes were of a lower magnitude compared to those from the time of surgery. In conclusion, vitamin D improved NO-dependent arteriolar vasodilation in obese adults; this effect was more significant before surgery-induced weight loss.

No abstract

Patients with obesity have limited access to kidney transplantation, mainly due to an increased incidence of surgical complications, which could be reduced with selective use of robotic‐assisted surgery. This prospective randomized controlled trial compares the safety and efficacy of combining robotic sleeve gastrectomy and robotic‐assisted kidney transplant to robotic kidney transplant alone in candidates with class II or III obesity. Twenty candidates were recruited, 11 were randomized to the robotic sleeve gastrectomy and robotic‐assisted kidney transplant group and 9 to the robotic kidney transplant group. At 12‐month follow‐up, change in body mass index was –8.76 ± 1.82 in the robotic sleeve gastrectomy and robotic‐assisted kidney transplant group compared to 1.70 ± 2.30 in the robotic kidney transplant group (P = .0041). Estimated glomerular filtration rate, serum creatinine, readmission rates, and graft failure rates up to 12 months were not different between the two groups. Length of surgery was longer in the robotic sleeve gastrectomy and robotic‐assisted kidney transplant group (405 minutes vs. 269 minutes, p = .00304) without increase in estimated blood loss (120 ml vs. 117 ml, p = .908) or incidence of surgical complications. Combined robotic‐assisted kidney transplant and sleeve gastrectomy is safe and effective compared to robotic‐assisted kidney transplant alone.