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The extracellular matrix (ECM) plays an important role in the maintenance of white adipose tissue (WAT) architecture and function, and proper ECM remodeling is critical to support WAT malleability to accommodate changes in energy storage needs. Obesity and adipocyte hypertrophy place a strain on the ECM remodeling machinery, which may promote disordered ECM and altered tissue integrity and could promote proinflammatory and cell stress signals. To explore these questions, new methods were developed to quantify omental and subcutaneous WAT tensile strength and WAT collagen content by three-dimensional confocal imaging, using collagen VI knockout mice as a methods validation tool. These methods, combined with comprehensive measurement of WAT ECM proteolytic enzymes, transcript, and blood analyte analyses, were used to identify unique pathophenotypes of metabolic syndrome and type 2 diabetes mellitus in obese women, using multivariate statistical modeling and univariate comparisons with weight-matched healthy obese individuals. In addition to the expected differences in inflammation and glycemic control, approximately 20 ECM-related factors, including omental tensile strength, collagen, and enzyme transcripts, helped discriminate metabolically compromised obesity. This is consistent with the hypothesis that WAT ECM physiology is intimately linked to metabolic health in obese humans, and the studies provide new tools to explore this relationship.

Context: Mouse studies suggest that adropin, a peptide hormone, is required for metabolic homeostasis and prevention of obesity-associated insulin resistance. Whether obesity and insulin resistance are associated with low plasma adropin levels in humans is not known., Objectives: Our objective was to investigate the hypothesis that obesity and indicators of insulin resistance are associated with low adropin levels and determine whether weight loss regulates adropin levels., Design and Participants: Plasma was obtained from 85 female [age 21-67 yr, body mass index (BMI) 19.4-71.5 kg/m2] and 45 male (age 18-70 yr, BMI 19.1-62.6 kg/m2) volunteers for other clinical studies. The impact of Roux-en-Y gastric bypass was investigated in 19 obese females (BMI 37-65 kg/m2) using samples collected at baseline and 1-12 months after surgery., Results: Adropin levels correlate negatively with BMI (r=-0.335, P<0.001) and age (r=-0.263, P=0.003). Age-adjusted adropin levels are higher in males [4.1 ng/ml; 95% confidence interval (CI)=3.6-4.6 ng/ml] than females (3.0 ng/ml; 95% CI=2.6-3.4 ng/ml) (P=0.001). In all subjects, lower age-adjusted adropin levels were observed in overweight (3.3 ng/ml; 95% CI=2.8-3.8 ng/ml, P=0.033) and obese (2.7 ng/ml; 95% CI=2.1-3.3 ng/ml, P=0.001) compared with healthy-weight subjects (4.1 ng/ml; 95% CI=3.6-4.5 ng/ml). This effect was gender specific (weight category×gender, P<0.001) and was observed in males only. Aging and diagnosis with two or more metabolic syndrome risk factors was associated with low adropin levels, irrespective of sex. Adropin concentrations increased after Roux-en-Y gastric bypass, peaking 3 months after surgery (P<0.01)., Conclusions: Although males exhibit higher adropin levels that are reduced by obesity, aging and markers of insulin resistance are associated with low plasma adropin irrespective of sex.

Obesity has become a major public health concern in the United States and the rest of the world. This disease carries significant health risks that encompass several organ systems. Type 2 diabetes mellitus is a major comorbidity of obesity that predisposes patients to significant end-organ damage. The prevalence of obesity and diabetes is increasing worldwide, and the economic impact of these diseases currently assumes a significant portion of health care expenditure. These factors mandate implementation of therapeutic medical and surgical strategies that target prevention and treatment of obesity and its related medical conditions., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: The purpose of this study was to evaluate the natural history of patients undergoing Roux-en-Y gastric bypass (RYGBP) with known asymptomatic cholelithiasis in whom prophylactic cholecystectomy was not performed at the time of surgery., Methods: The records of 144 consecutive patients from a single year experience in RYGBP surgery at the University of California, Davis Medical Center were reviewed. Patients undergoing RYGBP were routinely screened for cholelithiasis by ultrasound. Patients who did not have cholecystectomy were managed with ursodiol for 6 months postoperatively., Results: 13 males (9.0%) and 131 females (91%) underwent RYGBP. The mean age was 43 years (SD 8.55), and mean BMI was 46 kg/m2 (SD 6.5). The comorbidities of our patient population included diabetes (14%), hypertension (48%), gastroesophageal reflux disease (50%), dyslipidemia (35%), obstructive sleep apnea (31%), and musculoskeletal complaints (69%). 22 patients were diagnosed with cholelithiasis by ultrasonography preoperatively. 9 of these patients (41%) were symptomatic and underwent concurrent cholecystectomy and RYGBP. The remaining 13 patients (59%) had asymptomatic cholelithiasis preoperatively but did not undergo cholecystectomy at the time of surgery. Only one of these asymptomatic patients eventually developed symptoms necessitating cholecystectomy at up to 1 year follow-up., Conclusions: Our data suggest that it may not be absolutely indicated to perform prophylactic cholecystectomy at the time of RYGBP surgery for asymptomatic cholelithiasis. We believe that this phenomenon needs to be further studied in a randomized trial.

Aims/hypothesisBariatric surgery is an effective treatment for severe obesity, as in addition to dramatic weight loss, co-morbidities such as type 2 diabetes are frequently resolved. Although altered gastrointestinal peptide hormone secretion and its relationship with post-surgical improvements in insulin sensitivity has been studied, much less is known about long-term changes in pancreatic and adipose tissue-derived hormones. Our objective was to conduct a comprehensive longitudinal investigation of the endocrine changes following Roux-en-Y gastric bypass surgery (RYGBP), focusing on pancreatic and adipocyte hormones and systemic markers of inflammation.MethodsNineteen severely obese women (BMI 45.6 +/- 1.6 kg/m(2)) were studied prior to RYGBP, and at 1, 3, 6, and 12 months after RYGBP. Body composition was assessed before surgery and at 1 and 12 months.ResultsPre-surgical adiposity was correlated with circulating adipocyte hormones (leptin, visfatin) and inflammatory molecules (IL-6, high sensitivity C-reactive protein [hsCRP], monocyte chemoattractant protein-1). As expected, RYGBP reduced fat mass and fasting insulin and glucose concentrations. In addition, reductions of fasting pancreatic polypeptide (PP) and glucagon concentrations were observed at 1 and 3 months, respectively. In the 12 months following RYGBP, concentrations of most adipocyte hormones (leptin, acylation-stimulating hormone and visfatin, but not retinol-binding hormone-4) and inflammatory molecules (IL-6, hsCRP and soluble intracellular adhesion molecule-1) were significantly reduced. Reductions of insulin resistance (measured by homeostasis model assessment of insulin resistance) were independently associated with changes of glucagon, visfatin and PP. Pre-surgical HMW adiponectin concentrations independently predicted losses of body weight and fat mass.Conclusions/interpretationThese results suggest that pancreatic and adipocyte hormones may contribute to the long-term resolution of insulin resistance after RYGBP.

Aims/hypothesisIn addition to weight loss, bariatric surgery for severe obesity dramatically alleviates insulin resistance. In this study, we investigated whether circulating concentrations of the high-molecular-weight (HMW) form of adiponectin are increased following gastric bypass surgery. The HMW form is implicated as the multimer responsible for adiponectin's hepatic insulin-sensitising actions.Subjects and methodsWe studied 19 women who were undergoing Roux-en-Y gastric bypass surgery. Studies were conducted prior to, and 1 and 12 months after surgery.ResultsOne month after surgery, total plasma adiponectin concentrations were unchanged. Nevertheless, increases in both HMW (by 40+/-15%, p=0.006) and the proportion of adiponectin in the HMW form (from 40+/-2 to 50+/-2%, p