Micronutrient status 2 years after bariatric surgery: a prospective nutritional assessment.

Background: Among commonly performed bariatric surgeries, biliopancreatic diversion with duodenal switch (BPD-DS) provides greater weight loss than Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG), with sustained metabolic improvements. However, the risk of long-term nutritional deficiencies due to the hypoabsorptive component of BPD-DS hinders its widespread use. Objective: The aim of the study was to examine nutritional status over 2 years after BPD-DS, RYGB or SG. Methods: Patients were recruited in the REMISSION trial (NCT02390973), a single-center, prospective study. Out of 215 patients, 73, 48 and 94, respectively, underwent BPD-DS, RYGB or SG. Weight loss, micronutrient serum levels (including iron, calcium, parathormone, vitamins A, B12 and D), and nutritional supplementation were assessed over 2 years. Patients were supplemented according to the type of surgery and individual micronutrient level evolution. Results: At baseline, BPD-DS patients were younger than SG patients (p = 0.0051) and RYGB patients had lower body mass index (p < 0.001). Groups had similar micronutrient levels before surgery, with vitamin D insufficiency as the most prevalent nutritional problem (SG: 38.3%, RYGB: 39.9%, BPD-DS: 54.8%, p = 0.08). BPD-DS patients showed lower levels of iron, calcium and vitamin A than SG patients at 24 months. Groups had similar levels of vitamin D at 24 months. Prevalence of vitamin D, calcium, iron, vitamin A and vitamin B12 deficiency was similar among groups at 24 months. Rates of vitamin D insufficiency and iron deficiency were lower at 24 months than at baseline. Micronutrient intake was consistent with recommendations in groups post-surgery, but most BPD-DS patients took vitamin A and vitamin D supplement doses above initial recommendations. Conclusion: With appropriate medical and nutritional management, all surgeries led to similar rates of vitamin D, calcium, iron, vitamin A and vitamin B12 deficiencies at 24 months. However, initial vitamin A and vitamin D supplementation recommendations for BPD-DS patients should be revised upwards.

Prevalence of Helicobacter pylori Infection in Bariatric Surgery Patients.

OBJECTIVE: To determine the rate of histology-proven Helicobacter pylori (HP) infection in patients undergoing bariatric surgery and to identify risk factors for HP infection. METHODS: In a retrospective analysis, patients who underwent bariatric surgery with gastric resection in a single hospital between January 2004 and January 2019 were analyzed. For each patient, a surgical specimen was submitted for anatomopathological examination and analyzed for gastritis or other anomalies. When gastritis was present, HP infection was confirmed by the identification of curvilinear bacilli in conventional histology or by specific immunohistochemical detection of HP antigen. RESULTS: A total of 6388 specimens were available for review (4365 women, 2023 men) with a mean age of 44.9 ± 11.2 years and a mean body mass index (BMI) of 49.3 ± 8.2 kg/m2. Histology-proven HP infection rate was 6.3% (n = 405). There was no significant difference in sex, BMI, and body weight between HP + and HP - patients. Logistic regressions identified age as a risk factor for HP infection in this population (OR 1.02, p < 0.0001, CI 95% 1.01-1.03 for every 1-year increase, OR 1.26, p < 0.0001, CI 95% 1.14-1.40 for every 10-year increase). CONCLUSIONS: The rate of histology-proven HP infection is low in patients with severe obesity who present for bariatric surgery and is associated with age.

Bariatric Surgery Should Be Offered to Active-Duty Military Personnel: a Retrospective Study of the Canadian Armed Forces' Experience.

PURPOSE: Like most Western armies, obesity affects Canadian Armed Forces (CAF) personnel. Bariatric surgery is an effective treatment for obesity. However, this is not yet accepted for active-duty soldiers in most countries. The CAF have approved bariatric surgery since 2005. Our aim is to assess weight loss, resolution of obesity-related comorbidities, and impacts of bariatric surgery on military careers. MATERIALS AND METHODS: We retrospectively reviewed the perioperative data, long-term bariatric results, and military outcomes of 108 CAF active-duty military personnel who underwent bariatric surgery in Canada over a 61-month period. RESULTS: The cohort was predominantly male (66.7%) with a mean preoperative body mass index (BMI) of 43.6 ± 5.8 kg/m2. Roux-Y gastric bypass was performed in 59 patients, sleeve gastrectomy in 29, and gastric banding in 20. All the surgeries were performed laparoscopically. The total body weight loss at the last follow-up visit was 22.5 ± 11.0%. Remission or improvement of hypertension was observed in 91.2%, diabetes in 85.7%, gastroesophageal reflux disorder (GERD) in 43.6%, sleep apnea in 43.1%, and dyslipidemia in 42.9%. One patient (0.9%) was medically released due to postoperative complications. Fifteen patients (13.9%) were deployed postoperatively. The combined deployable and possibly deployable statuses increased from 35.4% preoperatively to 47.9% postoperatively. CONCLUSION: This is the largest series of bariatric surgeries performed in active-duty military personnel. Bariatric surgery is effective and safe and improves deployability without impairing military careers. These results are relevant to the military of many industrialized countries. Bariatric surgery should be considered for all active-duty military personnel who meet surgical criteria for the treatment of obesity.

Exploring Clinical Risk Factors for Breast Cancer Among American Indian Women.

Objective: Very little is known about the breast cancer risk profile among American Indian women. Previous research shows that the proportion of American Indian/Alaska Native women with baseline characteristics (commonly known breast cancer risk factors) differs from other ethnicities. This retrospective case control study was designed to the explore the association of these factors among American Indian women with and without breast cancer. Methods: Cases and controls were retrospectively selected from the medical records of American Indian women who obtained their health care from Quentin N. Burdick Memorial Health Care Facility (Indian Health Service) in Belcourt, ND. For each woman with breast cancer (n = 141), two controls were selected when possible (n = 278). Risk factors examined included woman's age, age at first live birth, age of menarche, the number of previous benign breast biopsies, the total number of first-degree relatives with breast cancer, body mass index and parity. Odds ratios and 95% confidence intervals were calculated using logistic regression. Results: Many of the associations found among American Indian women who obtained their health care from Quentin N. Burdick Memorial Health Care Facility (Indian Health Service) in Belcourt, ND, between risk factors commonly identified in other populations and breast cancer were weakly positive. Nulliparity was the only risk factor to consistently show a positive significant association (OR = 2.87, 95% CI 1.16-0.7.12). Conclusion: Disparities in breast cancer incidence, mortality and screening among Northern Plains American Indian emphasize the need to better understand the risk factors associated with breast cancer in this population. Based on the results of this study, the value of current risk prediction models in American Indian communities is uncertain and clinicians should be cautious in using these models to inform American Indian patients of their risk for breast cancer.

Molecular remodeling of adipose tissue is associated with metabolic recovery after weight loss surgery.

BACKGROUND: Bariatric surgery is an effective therapy for individuals with severe obesity to achieve sustainable weight loss and to reduce comorbidities. Examining the molecular signature of subcutaneous adipose tissue (SAT) following different types of bariatric surgery may help in gaining further insight into their distinct metabolic impact. RESULTS: Subjects undergoing biliopancreatic diversion with duodenal switch (BPD-DS) showed a significantly higher percentage of total weight loss than those undergoing gastric bypass or sleeve gastrectomy (RYGB + SG) (41.7 ± 4.6 vs 28.2 ± 6.8%; p = 0.00005). Individuals losing more weight were also significantly more prone to achieve both type 2 diabetes and dyslipidemia remission (OR = 0.75; 95%CI = 0.51-0.91; p = 0.03). Whole transcriptome and methylome profiling showed that bariatric surgery induced a profound molecular remodeling of SAT at 12 months postoperative, mainly through gene down-regulation and hypermethylation. The extent of changes observed was greater following BPD-DS, with 61.1% and 49.8% of up- and down-regulated genes, as well as 85.7% and 70.4% of hyper- and hypomethylated genes being exclusive to this procedure, and mostly associated with a marked decrease of immune and inflammatory responses. Weight loss was strongly associated with genes being simultaneously differentially expressed and methylated in BPD-DS, with the strongest association being observed for GPD1L (r2 = 0.83; p = 1.4 × 10-6). CONCLUSIONS: Present findings point to the greater SAT molecular remodeling following BPD-DS as potentially linked with higher metabolic remission rates. These results will contribute to a better understanding of the metabolic pathways involved in the response to bariatric surgery and will eventually lead to the development of gene targets for the treatment of obesity. Trial registration ClinicalTrials.gov NCT02390973.

Identification of Cancer Related Risk and Protective Factors for American Indian Youth: A Mixed Studies Review.

Introduction: Many causes of cancer related morbidity and mortality can be traced back to childhood behaviors. The culmination of cancer related risk and protective factors impacting the health and wellbeing of American Indian youth is unknown. The aim of this Mixed Studies Review was to identify cancer related risk and protective factors among American Indian youth. Results will be shared with Tribal communities to inform surveillance efforts. Methods: A Mixed Studies Review process was deemed most appropriate for the search process and data collection. Seven databases were included in the search along with 3 databases that were hand searched. Google Scholar and Google power searching were also conducted. Covidence was utilized for abstract and full-text review. Out of 1,512 articles, 75 articles were included for review and data from each article was sorted out into the levels of the social ecological model. Results: After extracting significant cancer related risk and protective factors from the 75 relevant articles, cancer related themes were identified at the individual, relationship (family and non-family), community, institutional, and cultural levels of the social ecological model. It was observed that the risk and protective factor profile for substance use spanned all levels of the social ecological model, whereas physical health-diet indicators and sexual health indicators did not. Most articles (n = 58, 77%) focused on substance use-related risk and protective factors. Discussion: The method that was used for this study can be utilized by other professionals researching risk and protective factors impacting the health and wellbeing of American Indian youth for a multitude of health outcomes. Tribal communities will be able to use the results from our literature review to inform the creation of a community specific data collection tool focused on cancer related risk and protective factors. Upon completion of the overarching research, results will be shared with the community and can be used to inform ongoing surveillance efforts, influence priorities for intervention and education work, and inform the management of resources. The continuation of community informed and driven research with Tribal communities is essential to the health and wellbeing of Tribal Nations as community grounded research is limited.

Spontaneous neural activity changes after bariatric surgery: A resting-state fMRI study.

BACKGROUND: Metabolic disorders associated with obesity could lead to alterations in brain structure and function. Whether these changes can be reversed after weight loss is unclear. Bariatric surgery provides a unique opportunity to address these questions because it induces marked weight loss and metabolic improvements which in turn may impact the brain in a longitudinal fashion. Previous studies found widespread changes in grey matter (GM) and white matter (WM) after bariatric surgery. However, findings regarding changes in spontaneous neural activity following surgery, as assessed with the fractional amplitude of low frequency fluctuations (fALFF) and regional homogeneity of neural activity (ReHo), are scarce and heterogenous. In this study, we used a longitudinal design to examine the changes in spontaneous neural activity after bariatric surgery (comparing pre- to post-surgery), and to determine whether these changes are related to cardiometabolic variables. METHODS: The study included 57 participants with severe obesity (mean BMI=43.1 ± 4.3 kg/m2) who underwent sleeve gastrectomy (SG), biliopancreatic diversion with duodenal switch (BPD), or Roux-en-Y gastric bypass (RYGB), scanned prior to bariatric surgery and at follow-up visits of 4 months (N = 36), 12 months (N = 29), and 24 months (N = 14) after surgery. We examined fALFF and ReHo measures across 1022 cortical and subcortical regions (based on combined Schaeffer-Xiao parcellations) using a linear mixed effect model. Voxel-based morphometry (VBM) based on T1-weighted images was also used to measure GM density in the same regions. We also used an independent sample from the Human Connectome Project (HCP) to assess regional differences between individuals who had normal-weight (N = 46) or severe obesity (N = 46). RESULTS: We found a global increase in the fALFF signal with greater increase within dorsolateral prefrontal cortex, precuneus, inferior temporal gyrus, and visual cortex. This effect was more significant 4 months after surgery. The increase within dorsolateral prefrontal cortex, temporal gyrus, and visual cortex was more limited after 12 months and only present in the visual cortex after 24 months. These increases in neural activity measured by fALFF were also significantly associated with the increase in GM density following surgery. Furthermore, the increase in neural activity was significantly related to post-surgery weight loss and improvement in cardiometabolic variables, such as blood pressure. In the independent HCP sample, normal-weight participants had higher global and regional fALFF signals, mainly in dorsolateral/medial frontal cortex, precuneus and middle/inferior temporal gyrus compared to the obese participants. These BMI-related differences in fALFF were associated with the increase in fALFF 4 months post-surgery especially in regions involved in control, default mode and dorsal attention networks. CONCLUSIONS: Bariatric surgery-induced weight loss and improvement in metabolic factors are associated with widespread global and regional increases in neural activity, as measured by fALFF signal. These findings alongside the higher fALFF signal in normal-weight participants compared to participants with severe obesity in an independent dataset suggest an early recovery in the neural activity signal level after the surgery.

IGFBP-2 partly mediates the early metabolic improvements caused by bariatric surgery.

Insulin-like growth factor-binding protein (IGFBP)-2 is a circulating biomarker of cardiometabolic health. Here, we report that circulating IGFBP-2 concentrations robustly increase after different bariatric procedures in humans, reaching higher levels after biliopancreatic diversion with duodenal switch (BPD-DS) than after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). This increase is closely associated with insulin sensitization. In mice and rats, BPD-DS and RYGB operations also increase circulating IGFBP-2 levels, which are not affected by SG or caloric restriction. In mice, Igfbp2 deficiency significantly impairs surgery-induced loss in adiposity and early improvement in insulin sensitivity but does not affect long-term enhancement in glucose homeostasis. This study demonstrates that the modulation of circulating IGFBP-2 may play a role in the early improvement of insulin sensitivity and loss of adiposity brought about by bariatric surgery.

Neuroanatomical changes in white and grey matter after sleeve gastrectomy.

BACKGROUND: MRI studies show that obese adults have reduced grey matter (GM) and white matter (WM) tissue density as well as altered WM integrity. Bariatric surgery can lead to substantial weight loss and improvements in metabolic parameters, but it remains to be examined if it induces structural brain changes. The aim of this study was to characterize GM and WM density changes measured with MRI in a longitudinal setting following sleeve gastrectomy, and to determine whether any changes are related to inflammation and cardiometabolic blood markers. METHODS: 29 participants with obesity (age: 45.9 â€‹± â€‹7.8 years) scheduled to undergo sleeve gastrectomy were recruited. High-resolution T1-weighted anatomical images were acquired 1 month prior to as well as 4 and 12 months after surgery. GM and WM densities were quantified using voxel-based morphometry (VBM). Circulating lipid profile, glucose, insulin and inflammatory markers (interleukin-6, C-reactive protein and lipopolysaccharide-binding protein) were measured at each time point. A linear mixed effect model was used to compare brain changes before and after SG, controlling for age, sex, initial BMI and diabetic status. To assess the associations between changes in adiposity, metabolism and inflammation and changes in GM or WM density, the mean GM and WM densities were extracted across all the participants using atlas-derived regions of interest, and linear mixed-effect models were used. RESULTS: As expected, weight, BMI, waist circumference and neck circumference significantly decreased after SG compared with baseline (p â€‹< â€‹0.001 for all). A widespread increase in WM density was observed after surgery, particularly in the cerebellum, brain stem, cerebellar peduncle, cingulum, corpus callosum and corona radiata (p â€‹< â€‹0.05, after FDR correction). Significant increases in GM density were observed 4 months after SG compared to baseline in several brain regions such as the bilateral occipital cortex, temporal cortex, postcentral gyrus, cerebellum, hippocampus and insula as well as right fusiform gyrus, right parahippocampal gyrus, right lingual gyrus and right amygdala. These GM and WM increases were more pronounced and widespread after 12 months and were significantly associated with post-operative weight loss and the improvement of metabolic alterations. A linear mixed-effect model also showed associations between post-operative reductions in lipopolysaccharide-binding protein, a marker of inflammation, and increased WM density. To confirm our results, we tested whether the peak of each significant region showed BMI-related differences in an independent dataset (Human Connectome Project). We matched a group of individuals who were severely obese with a group of individuals who were lean for age, sex and ethnicity. Severe obesity was associated with reduced WM density in the brain stem and cerebellar peduncle as well as reduced GM density in cerebellum, regions that significantly changed after surgery (p â€‹< â€‹0.01 for all clusters). CONCLUSIONS: Bariatric surgery-induced weight loss and improvement in metabolic alterations is associated with widespread increases in WM and GM densities. These post-operative changes overlapped with baseline brain differences between participants who were severely obese and those who were normal-weight in a separate dataset, which may suggest a recovery of WM and GM alterations after bariatric surgery.

Bariatric Surgery Rapidly Decreases Cardiac Dietary Fatty Acid Partitioning and Hepatic Insulin Resistance Through Increased Intra-abdominal Adipose Tissue Storage and Reduced Spillover in Type 2 Diabetes.

Reduced storage of dietary fatty acids (DFAs) in abdominal adipose tissues with enhanced cardiac partitioning has been shown in subjects with type 2 diabetes (T2D) and prediabetes. We measured DFA metabolism and organ partitioning using positron emission tomography with oral and intravenous long-chain fatty acid and glucose tracers during a standard liquid meal in 12 obese subjects with T2D before and 8-12 days after bariatric surgery (sleeve gastrectomy or sleeve gastrectomy and biliopancreatic diversion with duodenal switch). Bariatric surgery reduced cardiac DFA uptake from a median (standard uptake value [SUV]) 1.75 (interquartile range 1.39-2.57) before to 1.09 (1.04-1.53) after surgery (P = 0.01) and systemic DFA spillover from 56.7 mmol before to 24.7 mmol over 6 h after meal intake after surgery (P = 0.01), with a significant increase in intra-abdominal adipose tissue DFA uptake from 0.15 (0.04-0.31] before to 0.49 (0.20-0.59) SUV after surgery (P = 0.008). Hepatic insulin resistance was significantly reduced in close association with increased DFA storage in intra-abdominal adipose tissues (r = -0.79, P = 0.05) and reduced DFA spillover (r = 0.76, P = 0.01). We conclude that bariatric surgery in subjects with T2D rapidly reduces cardiac DFA partitioning and hepatic insulin resistance at least in part through increased intra-abdominal DFA storage and reduced spillover.

Pregnancy after Bariatric Surgery: Balancing Risks and Benefits.

The majority of bariatric surgeries in Canada are performed in women of reproductive age. Clinicians encounter more and more often pregnancies that occur after bariatric surgeries. The appropriate management and education of women who want to conceive after bariatric surgery is still unclear due to the lack of consistent data about maternal and neonatal outcomes following bariatric surgery. Maternal obesity during pregnancy confers a higher risk for gestational diabetes, hypertensive disorders, congenital malformations, prematurity and perinatal mortality. Generally, pregnancies in severely obese women who have undergone bariatric surgery are safe, and the women are at significantly lower risk for gestational diabetes, hypertensive disorders and large-for-gestational-age neonates, but the surgery confers a higher risk for small-for-gestational-age infants and prematurity. This review aims to provide evidence from recent publications about the risks and benefits of bariatric surgeries in the context of future pregnancies.

Influences and Practices in Colorectal Cancer Screening Among Health Care Providers Serving Northern Plains American Indians, 2011-2012.

INTRODUCTION: The epidemiology of colorectal cancer, including incidence, mortality, age of onset, stage of diagnosis, and screening, varies regionally among American Indians. The objective of the Improving Northern Plains American Indian Colorectal Cancer Screening study was to improve understanding of colorectal cancer screening among health care providers serving Northern Plains American Indians. METHODS: Data were collected, in person, from a sample of 145 health care providers at 27 health clinics across the Northern Plains from May 2011 through September 2012. Participants completed a 32-question, self-administered assessment designed to assess provider practices, screening perceptions, and knowledge. RESULTS: The proportion of providers who ordered or performed at least 1 colorectal cancer screening test for an asymptomatic, average-risk patient in the previous month was 95.9% (139 of 145). Of these 139 providers, 97.1% ordered colonoscopies, 12.9% ordered flexible sigmoidoscopies, 73.4% ordered 3-card, guaiac-based, fecal occult blood tests, and 21.6% ordered fecal immunochemical tests. Nearly two-thirds (64.7%) reported performing in-office guaiac-based fecal occult blood tests using digital rectal examination specimens. Providers who reported receiving a formal update on colorectal cancer screening during the previous 24 months were more likely to screen using digital rectal exam specimens than providers who had received a formal update on colorectal cancer screening more than 24 months prior (73.9% vs 56.9%, respectively, χ2 = 4.29, P = .04). CONCLUSION: Despite recommendations cautioning against the use of digital rectal examination specimens for colorectal cancer screening, the practice is common among providers serving Northern Plains American Indian populations. Accurate up-to-date, ongoing education for patients, the community, and health care providers is needed.

Biliopancreatic Diversion with Duodenal Switch in the Elderly: Long-Term Results of a Matched-Control Study.

BACKGROUND: Biliopancreatic diversion with duodenal switch (BPD-DS) is one of the most effective surgical approaches for the treatment of severe obesity. OBJECTIVE: The objective of this study is to compare perioperative complications and long-term results of open BPD-DS in elderly versus younger patients. METHODS: All patients aged 60 years and above who underwent a primary open BPD-DS in our center were selected (n = 105). Patients were matched 1:1 for sex, BMI, the presence of type 2 diabetes (T2DM), and year of surgery with a group of younger patients (aged ≤55 years). RESULTS: The mean age of the patients was 62.3 ± 2.0 vs. 40.4 ± 7.0 years (p ≤ 0.0001). Initial BMI and prevalence of T2DM were similar in both groups, at 50.9 kg/m(2) and 57%, respectively. Mean operative time (178.6 ± 46.7 vs. 162.5 ± 39.9 min, p = 0.01), hospital stay (10.2 ± 8.3 vs. 6.3 ± 1.5 days, p = 0.0001), and blood loss (593 ± 484 vs. 474 ± 241 ml, p = 0.05) were significantly higher in elderly patients. No difference in 30-day mortality rate was observed (0.9% in each group). There was no significant difference in major complication rate (16.2 vs. 8.6%, p = 0.09). At a mean follow-up of 7.1 ± 4.1 years, excess weight loss (67.6 ± 19.2 vs. 72.7 ± 20.7%, p = 0.06) and BMI (32.2 ± 5.7 vs. 30.8 ± 6.6 kg/m(2), p = 0.15) were not significantly different. No significant difference was observed between the two groups for the resolution of T2DM (p = 0.53) and obstructive sleep apnea (p = 0.44). CONCLUSIONS: Open BPD-DS is associated with similar long-term benefits in elderly and younger patients, in terms of weight loss and resolution or improvement of obesity-related comorbidities. Perioperative complications might be more frequent in the elderly population, but this was not associated with increased mortality.

Abdominal adipocyte populations in women with visceral obesity.

BACKGROUND: Visceral obesity is independently related to numerous cardiometabolic alterations, with adipose tissue dysfunction as a central feature. OBJECTIVE: To examine whether omental (OM) and subcutaneous (SC) adipocyte size populations in women relate to visceral obesity, cardiometabolic risk factors and adipocyte lipolysis independent of total adiposity. DESIGN AND METHODS: OM and SC fat samples were obtained during gynecological surgery in 60 women (mean age, 46.1±5.9 years; mean BMI, 27.1±4.5 kg/m² (range, 20.3-41.  kg/m²)). Fresh samples were treated with osmium tetroxide and were analyzed with a Multisizer Coulter. Cell size distributions were computed for each sample with exponential and Gaussian function fits. RESULTS: Computed tomography-measured visceral fat accumulation was the best predictor of larger cell populations as well as the percentage of small cells in both OM and SC fat (P<0.0001 for all). Accordingly, women with visceral obesity had larger cells in the main population and higher proportion of small adipocytes independent of total adiposity (P≤0.05). Using linear regression analysis, we found that women characterized by larger-than-predicted adipocytes in either OM or SC adipose tissue presented higher visceral adipose tissue area, increased percentage of small cells and homeostasis model assessment insulin resistance index as well as higher OM adipocyte isoproterenol-, forskolin- and dbcAMP-stimulated lipolysis compared to women with smaller-than-predicted adipocytes, independent of total adiposity (P≤0.05). CONCLUSION: Excess visceral adipose tissue accumulation is a strong marker of both adipocyte hypertrophy and increased number of small cells in either fat compartment, which relates to higher insulin resistance index and lipolytic response, independent of total adiposity.

Vitamin D reduces LPS-induced cytokine release in omental adipose tissue of women but not men.

CONTEXT: Both vitamin D deficiency and inflammation have been associated with insulin resistance and type 2 diabetes risk. In vitro vitamin D treatment of subcutaneous (SC) adipose tissue (AT) may reduce inflammation, but data are conflicting. OBJECTIVES: To evaluate the effects of vitamin D (25(OH)D3 and 1,25(OH)2D3) on the secretion of inflammatory cytokines (TNF-α and IL-6) in omental (OM) and SC human AT and to explore factors that could correlate with the individual response to vitamin D including age, smoking status, BMI, comorbidities, medication, HbA1c, apolipoprotein B, serum 25-hydroxyvitamin D and high sensitivity C-reactive protein. PATIENTS: 7 men and 8 women with severe obesity undergoing bariatric surgery. INTERVENTION: Fresh OM and SC AT explants sampled during surgery (n=15) were incubated for 24h in a control, 25(OH)D3 (150 nM) or 1,25(OH)2D3 (1 nM) medium. Lipopolysaccharide (LPS) (10 ng/ml) was added for another 24h. MAIN OUTCOME MEASURE: Change in TNF-α and IL-6 levels in collected media after vitamin D treatment (ELISA). RESULTS: Mean age and BMI of the patients were 46.4±10.9 years and 48.8±7.5 kg/m(2), respectively. Eleven patients had type 2 diabetes. 25(OH)D3 and 1,25(OH)2D3 reduced the LPS-induced increases in cytokine levels in OM AT of women but not in men. No effect was observed in SC AT. Apart from gender, none of the factors analyzed correlated with vitamin D response. CONCLUSION: We showed that 25(OH)D3 and 1,25(OH)2D3 can lower cytokine release from OM but not SC AT explants and only in women.

Alterations of plasma metabolite profiles related to adipose tissue distribution and cardiometabolic risk.

Metabolomic profiling of obese individuals revealed altered concentrations of many metabolites, especially branched-chain amino acids (BCAA), possibly linked to altered adipose tissue BCAA catabolism. We tested the hypothesis that some features of this metabolite signature relate closely to visceral obesity and concomitant alterations in cardiometabolic risk factors. We also postulated that alterations in BCAA-catabolizing enzymes are predominant in visceral adipose tissue. Fifty-nine women (BMI 20-41 kg/m(2)) undergoing gynecologic surgery were recruited and characterized for overall and regional adiposity, blood metabolite levels using targeted metabolomics, and cardiometabolic risk factors. Adipose samples (visceral and subcutaneous) were obtained and used for gene expression and Western blot analyses. Obese women had significantly higher circulating BCAA and kynurenine/tryptophan (Kyn/Trp) ratio than lean or overweight women (P < 0.01). Principal component analysis confirmed that factors related to AA and the Kyn/Trp ratio were positively associated with BMI, fat mass, visceral or subcutaneous adipose tissue area, and subcutaneous adipocyte size (P ≤ 0.05). AA-related factor was positively associated with HOMA-IR (P ≤ 0.01). Factors reflecting glycerophospholipids and sphingolipids levels were mostly associated with altered blood lipid concentrations (P ≤ 0.05). Glutamate level was the strongest independent predictor of visceral adipose tissue area (r = 0.46, P < 0.001). Obese women had lower expression and protein levels of BCAA-catabolizing enzymes in visceral adipose tissue than overweight or lean women (P ≤ 0.05). We conclude that among metabolites altered in obesity plasma concentrations of BCAA and the Kyn/Trp ratio are closely related to increased adiposity. Alterations in expression and protein levels of BCAA-catabolizing enzymes are predominant in visceral adipose tissue.

Updated survey of the steroid-converting enzymes in human adipose tissues.

Over the past decade, adipose tissues have been increasingly known for their endocrine properties, that is, their ability to secrete a number of adipocytokines that may exert local and/or systemic effects. In addition, adipose tissues have long been recognized as significant sites for steroid hormone transformation and action. We hereby provide an updated survey of the many steroid-converting enzymes that may be detected in human adipose tissues, their activities and potential roles. In addition to the now well-established role of aromatase and 11ß-hydroxysteroid dehydrogenase (HSD) type 1, many enzymes have been reported in adipocyte cell lines, isolated mature cells and/or preadipocytes. These include 11ß-HSD type 2, 17ß-HSDs, 3ß-HSD, 5α-reductases, sulfatases and glucuronosyltransferases. Some of these enzymes are postulated to bear relevance for adipose tissue physiology and perhaps for the pathophysiology of obesity. This elaborate set of steroid-converting enzymes in the cell types of adipose tissue deserves further scientific attention. Our work on 20α-HSD (AKR1C1), 3α-HSD type 3 (AKR1C2) and 17ß-HSD type 5 (AKR1C3) allowed us to clarify the relevance of these enzymes for some aspects of adipose tissue function. For example, down-regulation of AKR1C2 expression in preadipocytes seems to potentiate the inhibitory action of dihydrotestosterone on adipogenesis in this model. Many additional studies are warranted to assess the impact of intra-adipose steroid hormone conversions on adipose tissue functions and chronic conditions such as obesity, diabetes and cancer.

Circles of Tobacco Wisdom: learning about traditional and commercial tobacco with Native elders.

BACKGROUND: Circles of Tobacco Wisdom (CTW) was an elder-led, community-based project that aimed to enhance tobacco control in the American Indian community. Its goal was to provide elders with the knowledge, opportunities, and support to enable them to assume leadership of a tobacco control movement that was grounded in the ceremonial traditions of tobacco use. PURPOSE: The purpose of this study was to test the effects of the pilot intervention on participants. DESIGN: The design of this pilot study intervention was a single group, pre-post comparison, with a pre-post survey, monthly check-ins, and a post-1-year focus group. PARTICIPANTS: Twelve elders were included in the pre- and post-analyses. All twelve elders were women who self-identified as American Indian (mean age = 64). INTERVENTION: The CTW elders participated in monthly talking circles, quarterly learning sessions, and a post-1-year focus group, and took part in other learning, support, and community action opportunities. Data were collected from December 2008 through November 2009 and analyzed throughout the process. MAIN OUTCOME MEASURES: American Indian Elders' tobacco-related knowledge, perceptions, beliefs, and behaviors were measured while participating in the CTW project. RESULTS: Knowledge, perceptions, beliefs, and behavior changes were seen with cigarette smoking, secondhand smoke, and ceremonial tobacco use and risk perception. After 6 months, the number of people the elders had talked with about tobacco increased, elders were more likely to have a discussion on tobacco at a community event, and their comfort level talking about commercial and traditional tobacco also increased. A number of themes also were identified in the focus group: feeling more comfortable talking about tobacco issues, learning a lot about traditional and commercial tobacco, and realizing the dangers of smoking. CONCLUSIONS: Elders increased their knowledge about commercial and traditional tobacco and changed related attitudes as a result of CTW. Further, American Indian Elders perceived that CTW was effective.

Adipose tissue lamin A/C messenger RNA expression in women.

Mutations in the lamin A/C gene (LMNA) cause lipodystrophy. However, little data are available on lamin A/C expression in various fat depots in women. We recruited 34 women scheduled for gynecologic surgery. Blood samples were collected on the morning of surgery to obtain a detailed lipid profile. Radiological examinations were performed to measure total body fat mass and abdominal fat accumulation. Fat samples were taken from the subcutaneous (SC) fat depot and from the greater omentum (OM) during the surgical procedure. Whole adipose tissue samples were used for total messenger RNA (mRNA) extraction and real-time polymerase chain reaction quantification of the LMNA transcript. No association was observed between lamin A/C mRNA expression, either in SC or OM fat tissue, and adiposity measures. Women with low SC lamin A/C expression, identified on the basis of the median value of SC lamin A/C mRNA expression, had a significantly altered lipid profile including lower levels of high-density lipoprotein (HDL) cholesterol and HDL(2) cholesterol and reduced HDL(2) cholesterol to HDL(3) cholesterol ratio (P < .05 for all). These women were also characterized by higher cholesterol to HDL cholesterol, low-density lipoprotein-triglycerides, very low-density lipoprotein-apolipoprotein B, and low-density lipoprotein cholesterol to HDL cholesterol (P < .05 for all). Low SC lamin A/C mRNA expression levels were also associated with significantly increased lipolysis in isolated fat cells from this fat depot. Specifically, the response to lipolytic agent isoproterenol was significantly increased at doses ranging from 10(-5) to 10(-10) mol/L (P < .05). A similar trend was observed in OM fat cells but did not reach significance. In conclusion, low lamin A/C expression in SC adipose tissue is associated with significant alterations in the lipid profile and increased fat cell lipolysis, independent of the level of total or abdominal adiposity.

Pathways of adipose tissue androgen metabolism in women: depot differences and modulation by adipogenesis.

The objective was to examine pathways of androgen metabolism in abdominal adipose tissue in women. Abdominal subcutaneous (SC) and omental (OM) adipose tissue samples were surgically obtained in women. Total RNA was isolated from whole adipose tissue samples and from primary preadipocyte cultures before and after induction of differentiation. Expression levels of several steroid-converting enzyme transcripts were examined by real-time RT-PCR. Androgen conversion rates were also measured. We found higher expression levels in SC compared with OM adipose tissue for type 1 3beta-hydroxysteroid dehydrogenase (3beta-HSD-1; P < 0.05), for aldo-keto reductase 1C3 (AKR1C3; P < 0.0001), for AKR1C2 (P < 0.0001), and for the androgen receptor (P < 0.0001). 17beta-HSD-2 mRNA levels were lower in SC adipose tissue (P < 0.05). Induction of adipocyte differentiation led to significantly increased expression levels in SC cultures for AKR1C3 (4.7-fold, P < 0.01), 11-cis-retinol dehydrogenase (6.9-fold, P < 0.02), AKR1C2 (5.6-fold, P < 0.004), P-450 aromatase (5.7-fold, P < 0.02), steroid sulfatase (3.1-fold, P < 0.02), estrogen receptor-beta (11.8-fold, P < 0.01), and the androgen receptor (4.0-fold, P < 0.0005). Generally similar but nonsignificant trends were obtained in OM cultures. DHT inactivation rates increased with differentiation, this effect being mediated by dexamethasone alone, through a glucocorticoid receptor-dependent mechanism. In conclusion, higher mRNA levels of enzymes synthesizing and inactivating androgens are found in differentiated adipocytes, consistent with higher androgen-processing rates in these cells. Glucocorticoid-induced androgen inactivation may locally modulate the exposure of adipose cells to active androgens.