Biomechanical CT to Assess Bone After Sleeve Gastrectomy in Adolescents With Obesity: A Prospective Longitudinal Study.

Sleeve gastrectomy (SG) is effective in treating cardiometabolic complications of obesity but is associated with bone loss. Our aim was to determine the effect of SG on the lumbar spine by biomechanical CT analysis in adolescents/young adults with obesity. We hypothesized that SG would lead to a decrease in strength and bone mineral density (BMD) compared with nonsurgical controls. In a 12-month prospective nonrandomized study, adolescents/young adults with obesity underwent SG (n = 29, 18.0 ± 2.1 years, 23 female) or were followed without surgery (controls, n = 30, 17.95 ± 3.0 years, 22 female). At baseline and 12 months, participants underwent quantitative computed tomography (QCT) of L1 and L2 for biomechanical assessment and MRI of the abdomen and mid-thigh for body composition assessment. Twelve-month changes between groups and within groups were assessed. Analyses were controlled for baseline and 12-month changes in body mass index (BMI) by multivariable analyses. Regression analysis was performed to evaluate the effect of body composition on bone parameters. Our institutional review board (IRB) approved the study, and informed consent/assent was obtained. Participants in the SG group had a higher baseline BMI than controls (p = 0.01) and lost an average of 34.3 ± 13.6 kg 12 months after surgery, whereas weight was unchanged in controls (p < 0.001). There were significant reductions in abdominal adipose tissue and thigh muscle area in the SG group compared with controls (p < 0.001). Bone strength, bending stiffness, and average and trabecular volumetric BMD decreased in the SG group compared with controls (p < 0.001). After controlling for change in BMI, a 12-month reduction in cortical BMD was significant in the SG group compared with controls (p = 0.02). Reductions in strength and trabecular BMD were associated with reductions in BMI, visceral adipose tissue, and muscle (p ≤ 0.03). In conclusion, SG in adolescents decreased strength and volumetric BMD of the lumbar spine compared with nonsurgical controls. These changes were associated with decreases in visceral fat and muscle mass. © 2023 American Society for Bone and Mineral Research (ASBMR).

Skeletal Effects of Sleeve Gastrectomy in Adolescents and Young Adults: A 2-Year Longitudinal Study.

CONTEXT: Vertical sleeve gastrectomy (VSG) is an increasingly common tool to achieve weight loss and improve metabolic health in adolescents and young adults with obesity, although it may adversely affect bone health. OBJECTIVE: This work aimed to evaluate the effect of VSG on bone health in youth. METHODS: An observational 2-year study was conducted at a tertiary care center of 66 patients aged 13 to 24 years with moderate-to-severe obesity meeting criteria for VSG. The patients underwent VSG (n = 30) or nonsurgical (n = 36) management per the decision of patient and clinical team. Main outcome measures included dual-energy x-ray absorptiometry (DXA) and high-resolution peripheral quantitative computed tomography (HRpQCT) measures of bone mineral density (BMD), geometry, and microarchitecture. RESULTS: VSG patients achieved 25.3 ± 2.0% weight loss at 2 years (P < .001) while control subjects gained 4.0 ± 2.0% (P = .026). Total hip BMD declined 8.5 ± 1.0% following VSG compared with 0.1 ± 1.0% gain in controls (P < .001), with similar results at the femoral neck (P < .001). Total volumetric BMD (vBMD) decreased both at the distal radius and tibia following VSG (P < .001) driven primarily by trabecular vBMD loss (P < .001). Two-year changes in cortical vBMD did not differ between groups, though cortical porosity decreased following VSG both at the radius and tibia (P = .048 and P < .001). Cortical thickness increased in controls but not in VSG (P = .022 and P = .002 for between-group comparisons at the radius and tibia, respectively). Following VSG, estimated failure load decreased at the radius and did not demonstrate the physiologic increases at the tibia observed in controls. CONCLUSION: VSG leads to progressive changes in bone health over 2 years, and may lead to increased skeletal fragility in adolescents and young adults.

Comparison of weight loss outcomes between Roux-en-Y gastric bypass and sleeve gastrectomy in a racially mixed urban patient population.

BACKGROUND: National data show a trend favoring laparoscopic sleeve gastrectomy (SG) over Roux-en-Y gastric bypass (RYGB). Published data demonstrating the differences in weight loss between the two procedures are mixed. OBJECTIVE: In this retrospective study using clinical data from 2010 to 2020, we compared the clinical and demographic characteristics of patients undergoing either SG or RYGB to evaluate their long-term weight loss outcomes. SETTING: University hospital in the United States. METHODS: A total of 3329 patients were identified in our institutional Metabolic and Bariatric Surgery Accreditation and Quality Improvement database using Current Procedural Terminology codes for either RYGB or SG. A general linear model was used for baseline characteristics. Logistic regression was used for factors favoring RYGB versus SG. A multivariable linear mixed model was used for weight-trajectory analysis. Cox regression was used for a cumulative hazard ratio of 10% weight regained from nadir. RESULTS: Factors favoring RYGB were diagnoses of type 2 diabetes and gastroesophageal reflux disease, Hispanic ethnicity, and surgeon's preference. SG was favored among Black patients and smokers. RYGB was associated with more weight loss at all time points. The risk of weight regain was significantly higher after SG versus RYGB. CONCLUSIONS: The bariatric procedure choice is significantly influenced by race, medical history, and surgeon's experience. RYGB results in a significantly more durable weight loss compared with SG regardless of race or other stratification factors.

The impact of English proficiency on outcomes after bariatric surgery.

BACKGROUND: Several studies demonstrated language that discordant care between may lead to mixed outcomes and increased use of hospital-resources. In the setting of bariatric surgery, which relies heavily on intensive pre-operative and post-operative counseling, we hypothesized that patients with LEP would have less favorable outcomes compared to English-proficient (EP) patients. METHODS: All patients 18 years and older, who underwent laparoscopic sleeve gastrectomy (SG) or laparoscopic gastric bypass (LGBP) from January 2013 to December 2017 were included. Language proficiency was determined by chart review for the use of an interpreter at least once during the study period. Outcomes of interest at 30-days and 1 year included: emergency department (ED) visits, readmission, length of stay (LOS), chief-complaint on readmission, and post-operative complications. Additionally, comorbidity remission and weight loss at one year was recorded. RESULTS: A total of 671 patients were categorized as LEP (40%) and spoke 6 unique languages. Within the 1 year post-operative period, EP patients presented to the ED more than LEP patients (23% vs. 14% p < 0.001). After multivariable regression for potential confounders this difference persisted; adjusted OR = 0.65 (95% CI 0.43-0.95; p = 0.029). However, despite more frequent ED visits by EP patients, there was no significant difference in readmission within one year; adjusted OR = 0.94 (95% CI 0.56-1.55; p = 0.50). Both groups demonstrated similar successful weight loss at 1 year: EP-31.85% (LGBP) and - 28.02% (SG) vs. LEP-30.17% (LGBP) and - 28.36% (SG). EP and LEP patients also had similar remission of obesity-related comorbidities. CONCLUSION: There were no differences in outcomes following bariatric surgery when comparing patients with limited English proficiency to those who are proficient in English. Bariatric surgical care can be delivered in a safe and effective manner with equivalent outcomes between patients who are and are not English-language proficient.

Application of the Caprini Risk Assessment Model to Select Patients for Extended Thromboembolism Prophylaxis After Sleeve Gastrectomy.

BACKGROUND: The Caprini risk assessment model is a well-validated tool that identifies patients who would benefit from extended venous thromboembolism (VTE) prophylaxis beyond hospital discharge. VTE, particularly portal mesenteric vein thrombosis (PMVT), is a potentially devastating complication of laparoscopic sleeve gastrectomy (LSG); therefore, we sought to examine whether the model can be safely applied to LSG patients. We hypothesized that its use can minimize the incidence of postoperative VTE, including PMVT, without increasing the likelihood of bleeding complications. MATERIALS AND METHODS: We conducted a retrospective chart review of those patients who underwent LSG at our institution from 2010 and 2018, at which time the Caprini risk assessment model was already our institutional standard. We determined the patients' Caprini scores at the time of discharge and whether patients at high risk of VTE were discharged from hospital on extended courses of VTE prophylaxis. We also recorded if bleeding complications or VTE events occurred in the first 180 days after LSG. RESULTS: Six hundred thirty-eight patients underwent LSG, including 521 (81.7%) women, with an average preoperative body mass index (BMI) of 44.4 kg/m2 (SD 6.8). One hundred fifty-eight (24.8%) patients had Caprini scores that warranted extended courses of VTE prophylaxis beyond hospital discharge. Three patients (0.47%) developed a postoperative VTE, but no patient developed PMVT. No bleeding complications were observed among patients who received extended VTE prophylaxis. CONCLUSION: The Caprini risk assessment model can effectively identify patients after LSG who might benefit from extended courses of VTE prophylaxis. Extended VTE prophylaxis does not seem to confer increased bleeding risk in this patient population.

Association of Bariatric Surgery With Vascular Outcomes.

Importance: Bariatric surgical weight loss is associated with reduced cardiovascular mortality; however, the mechanisms underlying this association are incompletely understood. Objectives: To identify variables associated with vascular remodeling after bariatric surgery and to examine how sex, race, and metabolic status are associated with microvascular and macrovascular outcomes. Design, Setting, and Participants: This population-based longitudinal cohort included 307 individuals who underwent bariatric surgery. Participants were enrolled in the bariatric weight loss program at Boston Medical Center, a large, multi-ethnic urban hospital, with presurgical and postsurgical assessments. Data were collected from December 11, 2001 to August 27, 2019. Data were analyzed in September 2019. Exposure: Bariatric surgery. Main Outcomes and Measures: Flow-mediated dilation (FMD) and reactive hyperemia (RH) (as measures of macrovascular and microvascular function, respectively) and clinical variables were measured preoperatively at baseline and at least once postoperatively within 12 months of the bariatric intervention. Results: A total of 307 participants with obesity (mean [SD] age, 42 [12] years; 246 [80%] women; 199 [65%] White; mean [SD] body mass index, 46 [8]) were enrolled in this study. Bariatric surgery was associated with significant weight loss and improved macrovascular and microvascular function across subgroups of sex, race, and traditional metabolic syndrome (mean [SD] pre- vs postsurgery weight: 126 [25] kg vs 104 [25] kg; P < .001; mean [SD] pre- vs postsurgery FMD: 9.1% [5.3] vs 10.2% [5.1]; P < .001; mean [SD] pre- vs postsurgery RH: 764% [400] vs 923% [412]; P < .001). Factors associated with change in vascular phenotype correlated most strongly with adiposity markers and several metabolic variables depending on vascular territory (eg, association of weight change with change in RH: estimate, -3.2; 95% CI, -4.7 to -1.8; association of hemoglobin A1c with change in FMD: estimate, -0.5; 95% CI, -0.95 to -0.05). While changes in macrovascular function among individuals with metabolically healthy obesity were not observed, the addition of biomarker assessment using high-sensitivity C-reactive protein plasma levels greater than 2 mg/dL identified participants with seemingly metabolically healthy obesity who had low-grade inflammation and achieved microvascular benefit from weight loss surgery. Conclusions and Relevance: The findings of this study suggest that bariatric intervention is associated with weight loss and favorable remodeling of the vasculature among a wide range of individuals with cardiovascular risk. Moreover, differences in arterial responses to weight loss surgery by metabolic status were identified, underscoring heterogeneity in physiological responses to adiposity change and potential activation of distinct pathological pathways in clinical subgroups. As such, individuals with metabolically healthy obesity represent a mixed population that may benefit from more refined phenotypic classification.

Surgical management of obstructing clot at the jejunojejunostomy after gastric bypass: a single center experience and literature review.

BACKGROUND: Roux-en-Y gastric bypass is a proven treatment for morbid obesity and its sequelae. Gastric bypass has a safe risk profile, but postoperative complications can be seen. We report on 10 cases of postoperative bleeding causing an obstructing clot at the jejunojejunostomy (JJ) occurring over a 9-year period. OBJECTIVES: The aim was to document presenting symptoms of obstructing clots at the JJ and to suggest a treatment approach to minimize complications. SETTING: University Hospital, United States METHODS: The local Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) database was queried for all patients undergoing reoperation after Roux-en-Y gastric bypass, from July 2009 until December 2019. All patients who were found to have postoperative bleeding causing an obstructing clot at the JJ were selected for retrospective medical-record review. RESULTS: The most common presenting symptoms were Hematocrit drop (10 of 10), nausea (9 of 10), abdominal pain (7 of 10), and hematemesis (4 of 10). There were 12 reoperations in the 10 patients, 10 of which were completed laparoscopically. Infectious complications were the most frequent morbidity in our patients; 4 patients developed abscesses. In all of these, the operative notes described gross spillage into the peritoneal cavity. In later cases, the remnant stomach was decompressed before reoperation, reducing spillage. CONCLUSIONS: Despite the low rate of obstructing clots at the JJ, without rapid recognition and reoperation, there is a risk for serious complications. Typical presenting symptoms include nausea and abdominal pain, which help differentiate it from other causes of decreased hematocrit. Diagnosis is commonly made with computerized tomographic (CT) scan. Decompression of a dilated remnant stomach before addressing the clot can prevent intraperitoneal spillage and subsequent abscess formation. Enterotomy creation and removal of clot is recommended, without fear of continued bleeding.

Use of a Laparoscopic Witzel Gastrostomy Without Gastropexy in Bariatric and General Surgery.

BACKGROUND: Gastrostomy placement is the preferred means of long-term enteral feeding for patients who cannot eat by mouth. During laparoscopic gastrostomy, it is standard to perform gastropexy, apposing visceral and parietal peritoneum. In some settings, due to altered anatomy from prior surgery, direct apposition of the stomach to the abdominal wall is not possible. This study reports a series of cases where laparoscopic gastrostomy was performed via a Witzel approach without gastropexy. METHODS: A retrospective chart review was performed of all patients at a tertiary academic medical center who underwent Witzel gastrostomy without gastropexy over a 3-year period. In each case, an 18-French tube was placed into the fundus of the stomach and secured with a purse-string suture. A 5-cm serosalized Witzel tunnel was created around the tube using running silk suture. No gastropexy was performed. RESULTS: Six patients underwent 7 Witzel gastrostomy procedures. In three cases, patients had undergone prior major upper abdominal surgery where adhesive disease prevented gastropexy. In the other four cases, the patients had undergone prior gastric bypass with antecolic antegastric position of the roux limb. No patient suffered leak of gastric contents into the peritoneum, and there were no postoperative complications or mortality related to the gastrostomy. CONCLUSION: In cases where enteral access is necessary, and where the stomach cannot reach the anterior abdominal wall for gastropexy due to prior surgeries, a Witzel gastrostomy without gastropexy is a safe option which resulted in no morbidity or mortality in our series.

Effects of Sleeve Gastrectomy on Bone Marrow Adipose Tissue in Adolescents and Young Adults with Obesity.

CONTEXT: Sleeve gastrectomy (SG), the most common metabolic and bariatric surgery in adolescents, is associated with bone loss. Marrow adipose tissue (MAT) is a dynamic endocrine organ that responds to changes in nutrition and might serve as a novel biomarker for bone health. Two types of MAT have been described, which differ in anatomic location-proximal regulated MAT vs distal constitutive MAT. OBJECTIVE: To determine the effects of SG on volumetric bone mineral density (vBMD) and MAT in adolescents with obesity. We hypothesized that SG would lead to a decrease in vBMD and differential changes in MAT. DESIGN: 12-month prospective study in 52 adolescents with moderate-to-severe obesity (38 female; mean age:17.5 ±â€…2.2 years; mean BMI 45.2 ±â€…7.0 kg/m2), comprising 26 subjects before and after SG and 26 nonsurgical controls. MAIN OUTCOME MEASURES: Lumbar vBMD by quantitative computed tomography; MAT of the lumbar spine, femur and tibia by proton magnetic resonance spectroscopy; abdominal fat and thigh muscle by magnetic resonance imaging. RESULTS: Adolescents lost 34.1 ±â€…13.1 kg after SG vs 0.3 ±â€…8.4 kg in the control group (P < 0.001). Lumbar vBMD decreased in the SG group (P = 0.04) and this change was associated with a reduction in weight and muscle area (P < 0.05) and an increase in lumbar MAT (P = 0.0002). MAT of the femur and tibia decreased after SG vs controls (P < 0.05); however, the differences were no longer significant after controlling for change in weight. CONCLUSION: SG in adolescents decreased lumbar vBMD associated with an increase in lumbar MAT and decrease in extremity MAT. This demonstrates differential changes of regulated MAT in the lumbar spine and constitutive MAT in the distal skeleton in adolescents in response to SG.

Impact of sleeve gastrectomy on hip structural analysis in adolescents and young adults with obesity.

BACKGROUND: Sleeve gastrectomy (SG), the most commonly performed metabolic and bariatric surgery, is associated with reductions in areal bone mineral density at multiple sites, and changes in bone structure at the distal radius and tibia without reductions in strength estimates at these peripheral sites. Data are lacking regarding effects on hip strength estimates. OBJECTIVE: To evaluate effects of SG on measures of hip structural analysis in adolescents and young adults over 12 months using dual-energy x-ray absorptiometry. SETTINGS: Translational and Clinical Research Center. METHODS: We enrolled 48 youth 14- to 22-years old with moderate-to-severe obesity; 24 underwent SG and 24 controls were followed without surgery (18 females, 6 males in each group). Hip structure was assessed using dual-energy x-ray absorptiometry at baseline and 12 months. Analyses are adjusted for age, sex, race, and the baseline bone measure. RESULTS: The SG group lost 25.9% weight versus .3% in controls. Compared with controls, SG had reductions in narrow neck, intertrochanteric and femoral shaft bone mineral density Z-scores (P ≤ .012). Furthermore, SG had greater reductions in narrow neck and intertrochanteric region (but not femoral shaft) cross-sectional area, cortical thickness, cross-sectional moment of inertia and section modulus, and increases in buckling ratio (P ≤ .039). Differences were attenuated after adjusting for 12-month body mass index change. At 12 months, differences were minimal after adjusting for age, sex, race, and weight. CONCLUSIONS: Over 12 months, SG had negative effects at the narrow neck and intertrochanteric regions of the hip, but not the femoral shaft. Reduced body mass index may compensate for these deleterious effects on bone.

The Mitigating Effect of Phentermine and Topiramate on Weight Regain After Roux-en-Y Gastric Bypass Surgery.

OBJECTIVE: Weight regain (WR) after Roux-en-Y gastric bypass surgery (RYGB) starts to occur 2 years after surgery, ultimately affecting at least 25% of patients. A limited number of studies have evaluated the impact of antiobesity medications (AOMs) on this phenomenon. METHODS: This study reviewed the electronic medical records of 1,196 patients who underwent RYGB between 2004 and 2015. WR was evaluated by comparing each patient's weight during subsequent postoperative office visits to nadir weight (lowest weight after RYGB, n = 760), taking into consideration the interval during which WR occurred. Patients who were prescribed AOMs and came to follow-up visits were classified as adherent users, whereas those who missed their follow-up visits were considered nonadherent. This study used a linear mixed model, Cox regression, and generalized equation estimator to determine the impact of AOMs on WR trajectory, hazard ratio for time to event, and odds ratio for repeated event occurrence, respectively. RESULTS: Despite the lack of a unified protocol for using AOMs, the three statistical models converged to show that phentermine and topiramate, used individually or in combination, can significantly reduce WR after RYGB. CONCLUSIONS: Phentermine and topiramate are effective in mitigating WR after RYGB. Further studies are needed to help ascertain optimal use of AOMs after bariatric surgery.

Bone outcomes following sleeve gastrectomy in adolescents and young adults with obesity versus non-surgical controls.

BACKGROUND: Sleeve gastrectomy is the most commonly performed weight loss surgery in adolescents with moderate-to-severe obesity. While studies in adults have reported on the deleterious effects of gastric bypass surgery on bone structure and strength estimates, data are lacking for the impact of sleeve gastrectomy on these measures in adolescents. OBJECTIVE: To evaluate the impact of sleeve gastrectomy on bone outcomes in adolescents and young adults over 12 months using dual energy X-ray absorptiometry (DXA) and high resolution peripheral quantitative computed tomography (HRpQCT). PARTICIPANTS AND METHODS: We enrolled 44 youth 14-22 years old with moderate to severe obesity; 22 underwent sleeve gastrectomy and 22 were followed without surgery (16 females and 6 males in each group). At baseline and 12 months, DXA was used to assess areal bone mineral density (aBMD), HRpQCT of the distal radius and tibia was performed to assess bone geometry, microarchitecture and volumetric BMD (vBMD), and finite element analysis to assess strength estimates (stiffness and failure load). These analyses were adjusted for age, sex, race and the bone measure at baseline. Fasting blood samples were assessed for calcium, phosphorus, and 25(OH) vitamin D (25OHD) levels. RESULTS: Over 12-months, the surgical group lost 27.2% of body weight compared to 0.1% in the non-surgical (control) group. Groups did not differ for changes in 25OHD levels (p = 0.186). Compared to controls, the surgical group had reductions in femoral neck and total hip aBMD Z-scores (p ≤ 0.0006). At the distal tibia, compared to controls, the surgical group had reductions in cortical area and thickness and trabecular number, and increases in trabecular area and separation (p ≤ 0.026). At the distal radius, the surgical group had greater reductions in trabecular vBMD, than controls (p = 0.010). The surgical group had an increase in cortical vBMD at both sites (p ≤ 0.040), possibly from a decrease in cortical porosity (p ≤ 0.024). Most, but not all, differences were attenuated after adjusting for 12-month change in BMI. Groups did not differ for changes in strength estimates over time, except that increases in tibial stiffness were lower in the surgical group (p = 0.044) after adjusting for 12-month change in BMI. CONCLUSIONS: Over 12 months, weight loss associated with sleeve gastrectomy in adolescents had negative effects on areal BMD and certain HRpQCT parameters. However, bone strength estimates remained stable, possibly because of a simultaneous decrease in cortical porosity and increase in cortical volumetric BMD. Additional research is necessary to determine the relative contribution(s) of weight loss and the metabolic effects of surgery on bone outcomes, and whether the observed effects on bone stabilize or progress over time.

Racial differences in lumbar marrow adipose tissue and volumetric bone mineral density in adolescents and young adults with obesity.

BACKGROUND: Areal bone mineral density (BMD) of the lumbar spine by DXA is greater in Black compared to White adolescents. Bone strength is determined not only by BMD but also its microenvironment, and marrow adipose tissue (MAT) has been shown to be an important determinant of skeletal integrity, independent of BMD. Racial differences in volumetric BMD (vBMD) and MAT in adolescents and young adults with obesity are unknown. OBJECTIVE: To assess racial differences in lumbar vBMD and MAT in Black and White adolescents and young adults with obesity and to assess body composition determinants of bone parameters. We hypothesized that Blacks will have higher vBMD and lower MAT of the lumbar spine compared to Whites. METHODS: The study group comprised 77 adolescents/young adults, 25 Black and 52 White, (mean age 18.2 ± 2.5 years, range 13 to 24 years) with moderate to severe obesity (mean body mass index (BMI) 46.2 ± 7.3 kg/m2, range 35.5 to 69.7 kg/m2). Groups were similar in age, BMI, and sex distribution (p > 0.84). Subjects underwent QCT of the lumbar spine (L1-L2) for assessment of vBMD with the use of a calibration phantom and 1H-MRS/MRI for quantification of lumbar MAT content (L1-L2) and abdominal fat and thigh muscle mass. Groups were compared by Student's t-test or Wilcoxon test. Correlation analysis was performed to assess associations between bone parameters and body composition. RESULTS: Black adolescents/young adults with obesity had higher vBMD compared to Whites (p < 0.0001), while there was no significant difference in lumbar MAT (p = 0.64). There were also no significant differences in body composition measures between groups (p ≥ 0.28). An inverse association between MAT and vBMD was observed in Whites (r = -0.47, P = 0.001) but not in Blacks (p = 0.6). There were no significant associations between body composition measures and bone parameters (p > 0.1). CONCLUSION: There are racial differences in lumbar vBMD in adolescents and young adults with moderate to severe obesity, with Blacks having higher vBMD than Whites, while there were no differences in MAT content. The known inverse association between BMD and MAT was only observed in Whites but not in Blacks, suggesting possible racial differences in stem cell differentiation into the bone and fat lineages.

Fat-Specific Protein 27 Regulation of Vascular Function in Human Obesity.

Background Pathophysiological mechanisms that connect obesity to cardiovascular disease are incompletely understood. FSP27 (Fat-specific protein 27) is a lipid droplet-associated protein that regulates lipolysis and insulin sensitivity in adipocytes. We unexpectedly discovered extensive FSP27 expression in human endothelial cells that is downregulated in association with visceral obesity. We sought to examine the functional role of FSP27 in the control of vascular phenotype. Methods and Results We biopsied paired subcutaneous and visceral fat depots from 61 obese individuals (body mass index 44±8 kg/m2, age 48±4 years) during planned bariatric surgery. We characterized depot-specific FSP27 expression in relation to adipose tissue microvascular insulin resistance, endothelial function and angiogenesis, and examined differential effects of FSP27 modification on vascular function. We observed markedly reduced vasodilator and angiogenic capacity of microvessels isolated from the visceral compared with subcutaneous adipose depots. Recombinant FSP27 and/or adenoviral FSP27 overexpression in human tissue increased endothelial nitric oxide synthase phosphorylation and nitric oxide production, and rescued vasomotor and angiogenic dysfunction (P<0.05), while siRNA-mediated FSP27 knockdown had opposite effects. Mechanistically, we observed that FSP27 interacts with vascular endothelial growth factor-A and exerts robust regulatory control over its expression. Lastly, in a subset of subjects followed longitudinally for 12±3 months after their bariatric surgery, 30% weight loss improved metabolic parameters and increased angiogenic capacity that correlated positively with increased FSP27 expression (r=0.79, P<0.05). Conclusions Our data strongly support a key role and functional significance of FSP27 as a critical endogenous modulator of human microvascular function that has not been previously described. FSP27 may serve as a previously unrecognized regulator of arteriolar vasomotor capacity and angiogenesis which are pivotal in the pathogenesis of cardiometabolic diseases linked to obesity.

Weight Recidivism After Roux-en-Y Gastric Bypass Surgery: An 11-Year Experience in a Multiethnic Medical Center.

OBJECTIVE: Weight recidivism following Roux-en-Y gastric bypass (RYGB) is common and is associated with recurrence of comorbidities. Studies with long-term follow-up of recidivism quantified by weight regain (WR) are lacking. A retrospective review of all RYGB at our center from 2004 to 2015 was performed to examine the effects of race and type 2 diabetes on WR following RYGB. METHODS: Multivariable linear mixed models were used for the effects of time and race on weight, WR relative to nadir weight (WR/nadir), and WR relative to maximal weight loss, and Cox regressions were used for low, moderate, and high WR/nadir. RESULTS: A total of 1,395 participants were identified. The sample was limited to African American (AA), Caucasian American (CA), and Hispanic American (HA) participants. The effects of time (P < 0.0001), race (P < 0.0001), and race × time interaction (P = 0.0008) on weight trajectory were significant. AA had significantly more WR than CA (P < 0.01). AA and HA had a higher hazard ratio for having low, moderate, and rapid WR/nadir. CONCLUSIONS: Racial disparities after RYGB include WR and particularly affect AA. Understanding the etiologic factors that contribute to these disparities is important to optimize the long-term clinical outcomes of bariatric surgery.

Oxidative modifications of mitochondrial complex II are associated with insulin resistance of visceral fat in obesity.

Obesity, particularly visceral adiposity, has been linked to mitochondrial dysfunction and increased oxidative stress, which have been suggested as mechanisms of insulin resistance. The mechanism(s) behind this remains incompletely understood. In this study, we hypothesized that mitochondrial complex II dysfunction plays a role in impaired insulin sensitivity in visceral adipose tissue of subjects with obesity. We obtained subcutaneous and visceral adipose tissue biopsies from 43 subjects with obesity (body mass index ≥ 30 kg/m2) during planned bariatric surgery. Compared with subcutaneous adipose tissue, visceral adipose tissue exhibited decreased complex II activity, which was restored with the reducing agent dithiothreitol (5 mM) ( P < 0.01). A biotin switch assay identified that cysteine oxidative posttranslational modifications (OPTM) in complex II subunit A (succinate dehydrogenase A) were increased in visceral vs. subcutaneous fat ( P < 0.05). Insulin treatment (100 nM) stimulated complex II activity in subcutaneous fat ( P < 0.05). In contrast, insulin treatment of visceral fat led to a decrease in complex II activity ( P < 0.01), which was restored with addition of the mitochondria-specific oxidant scavenger mito-TEMPO (10 µM). In a cohort of 10 subjects with severe obesity, surgical weight loss decreased OPTM and restored complex II activity, exclusively in the visceral depot. Mitochondrial complex II may be an unrecognized and novel mediator of insulin resistance associated with visceral adiposity. The activity of complex II is improved by weight loss, which may contribute to metabolic improvements associated with bariatric surgery.

Differential associations between appendicular and axial marrow adipose tissue with bone microarchitecture in adolescents and young adults with obesity.

Marrow adipose tissue (MAT) in humans is distributed differentially across age and skeletal site. We have shown impaired microarchitecture and reduced bone strength at appendicular sites in conditions associated with high MAT of the axial skeleton in adults (including conditions of over- and undernutrition). Data are lacking regarding differences in MAT content of the appendicular versus the axial skeleton, and its relationship with bone microarchitecture and strength. Furthermore, data are conspicuously lacking in adolescents, a time when hematopoietic marrow is progressively converted to fatty marrow. The purpose of our study was to examine differential associations between appendicular (distal tibia) and axial (lumbar spine) MAT and bone microarchitecture and strength estimates of the distal tibia in adolescents with obesity. We hypothesized that compared to MAT of the axial skeleton (lumbar spine), MAT of the appendicular skeleton (distal tibia) would show stronger associations with bone microarchitecture and strength estimates of the appendicular skeleton (distal tibia). We evaluated 32 adolescents and young adults (27 females) with obesity; with a mean age of 17.8 ±â€¯2.1 years and median body mass index (BMI) of 41.34 kg/m2, who underwent dual energy X-ray absorptiometry (DXA) for total fat mass, proton MR spectroscopy (1H-MRS) of the distal tibia and 4th lumbar vertebra for MAT, high resolution peripheral quantitative computed tomography (HR-pQCT) of the distal tibia for volumetric bone mineral density (vBMD) and microarchitecture, and micro finite element analysis (FEA) for distal tibial strength estimates. Linear correlations between bone parameters and MAT were determined using the Spearman or Pearson methods, depending on data distribution. Lumbar spine MAT was inversely associated with age (r = -0.36; p = 0.037). Total and trabecular vBMD and trabecular number at the distal tibia were inversely associated with MAT at the distal tibia (r = -0.39, p = 0.025; r = -0.51, p = 0.003; r = -0.42, p = 0.015 respectively) but not with lumbar spine MAT (r = -0.19, p = 0.27; r = -0.18, p = 0.3; r = 0.005, p = 0.97 respectively). In adolescents and young adults with obesity, the associations between MAT and appendicular bone parameters differ depending on the site of MAT assessment i.e. axial vs. appendicular. Studies evaluating these endpoints in adolescents and young adults with obesity should take the site of MAT assessment into consideration.