Interferon-gamma released from omental adipose tissue of insulin-resistant humans alters adipocyte phenotype and impairs response to insulin and adiponectin release.

BACKGROUND: Inflammatory factors derived from adipose tissue have been implicated in mediating insulin resistance in obesity. We sought to identify these using explanted human adipose tissue exposed to innate and adaptive immune stimuli. METHODS: Subcutaneous and omental adipose tissue from obese, insulin-resistant donors was cultured in the presence of macrophage and T-cell stimuli, and the conditioned medium tested for its ability to inhibit insulin-stimulated glucose uptake into human Simpson-Golabi-Behmel Syndrome (SGBS) adipocytes. The nature of the inhibitory factor in conditioned medium was characterized physicochemically, inferred by gene microarray analysis and confirmed by antibody neutralization. RESULTS: Conditioned medium from omental adipose tissue exposed to a combination of macrophage- and T-cell stimuli inhibited insulin action and adiponectin secretion in SGBS adipocytes. This effect was associated with a pronounced change in adipocyte morphology, characterized by a decreased number of lipid droplets of increased size. The bioactivity of conditioned medium was abolished by trypsin treatment and had a molecular weight of 46 kDa by gel filtration. SGBS adipocytes exposed to a bioactive medium expressed multiple gene transcripts regulated by interferon-gamma (IFN-γ). Recombinant human IFN-γ recapitulated the effects of the bioactive medium and neutralizing antibody against IFN-γ but not other candidate factors abrogated medium bioactivity. CONCLUSIONS: IFN-γ released from inflamed omental adipose tissue may contribute to the metabolic abnormalities seen in human obesity.

Weight loss after laparoscopic adjustable gastric band and resolution of the metabolic syndrome and its components.

BACKGROUND: Substantial weight loss in the setting of obesity has considerable metabolic benefits. Yet some studies have shown improvements in obesity-related metabolic comorbidities with more modest weight loss. By closely monitoring patients undergoing bariatric surgery, we aimed to determine the effects of weight loss on the metabolic syndrome and its components and determine the weight loss required for their resolution. METHODS: We performed a prospective observational study of obese participants with metabolic syndrome (Adult Treatment Panel III criteria) who underwent laparoscopic adjustable gastric banding. Participants were assessed for all criteria of the metabolic syndrome monthly for the first 9 months, then 3-monthly until 24 months. RESULTS: There were 89 participants with adequate longitudinal data. Baseline body mass index was 42.4±6.2 kg m-2 with an average age was 48.2±10.7 years. There were 56 (63%) women. Resolution of the metabolic syndrome occurred in 60 of the 89 participants (67%) at 12 months and 60 of the 75 participants (80%) at 24 months. The mean weight loss when metabolic syndrome resolved was 10.9±7.7% total body weight loss (TBWL). The median weight loss at which prevalence of disease halved was 7.0% TBWL (17.5% excess weight loss (EWL)) for hypertriglyceridaemia; 11% TBWL (26.1-28% EWL) for high-density lipoprotein cholesterol and hyperglycaemia; 20% TBWL (59.5% EWL) for hypertension and 29% TBWL (73.3% EWL) for waist circumference. The odds ratio for resolution of the metabolic syndrome with 10-12.5% TBWL was 2.09 (P=0.025), with increasing probability of resolution with more substantial weight loss. CONCLUSIONS: In obese participants with metabolic syndrome, a weight loss target of 10-12.5% TBWL (25-30% EWL) is a reasonable initial goal associated with significant odds of having metabolic benefits. If minimal improvements are seen with this initial target, additional weight loss substantially increases the probability of resolution.

GM3 ganglioside and phosphatidylethanolamine-containing lipids are adipose tissue markers of insulin resistance in obese women.

AIMS: The association between central obesity and insulin resistance reflects the properties of visceral adipose tissue. Our aim was to gain further insight into this association by analysing the lipid composition of subcutaneous and omental adipose tissue in obese women with and without insulin resistance. METHODS: Subcutaneous and omental adipose tissue and serum were obtained from 29 obese non-diabetic women, 13 of whom were hyperinsulinemic. Histology, lipid and gene profiling were performed. RESULTS: In omental adipose tissue of obese, insulin-resistant women, adipocyte hypertrophy and macrophage infiltration were accompanied by an increase in GM3 ganglioside and its synthesis enzyme ST3GAL5; in addition, phosphatidylethanolamine (PE) lipids were increased and their degradation enzyme, phosphatidylethanolamine methyl transferase (PEMT), decreased. ST3GAL5 was expressed predominantly in adipose stromovascular cells and PEMT in adipocytes. Insulin resistance was also associated with an increase in PE lipids in serum. INTERPRETATION: The relevance of these findings to insulin resistance in humans is supported by published mouse studies, in which adipocyte GM3 ganglioside, increased by the inflammatory cytokine tumour necrosis factor-α, impaired insulin action and PEMT was required for adipocyte lipid storage. Thus in visceral adipose tissue of obese humans, an increase in GM3 ganglioside secondary to inflammation may contribute to insulin resistance and a decrease in PEMT may be a compensatory response to adipocyte hypertrophy.

Controversies in bariatric surgery.

BACKGROUND: There are many controversies related to bariatric surgery. This review explores selected areas. METHODS: A combination of randomized clinical trials (RCTs), systematic reviews and expert opinion have been brought together to highlight areas of importance or conflict. RESULTS AND CONCLUSION: Metabolic surgery is an increasingly preferred term rather than bariatric or obesity surgery. Reporting should be standardized to include appropriate weight measures, valid disease measures and data on loss to follow-up. There are many putative mechanisms of effect of key bariatric procedures, but satiety and early satiation appear central. Weight loss must be durable. Long-term outcome studies (more than 10-year follow-up) show that biliopancreatic diversion is most effective, with 72 per cent excess weight loss (EWL). Roux-en-Y gastric bypass and laparoscopic adjustable gastric banding (LAGB) are equally effective, with 54 per cent EWL. There are no long-term data on vertical sleeve gastrectomy. Type II diabetes is a common and serious disease, usually associated with increased weight. Multiple RCTs have shown that bariatric surgery provides clear benefits over continuing with non-surgical therapies. The earlier the treatment, the more likely and durable will be the remission. Bariatric surgery should be available to all who are obese (body mass index over 30 kg/m(2) ). LAGB, a safe, effective, reversible outpatient procedure, is the author's preferred primary option.

Increased pyruvate dehydrogenase kinase expression in cultured myotubes from obese and diabetic individuals.

PURPOSE: To investigate the mechanisms of impairments in oxidative metabolism in obese and diabetic (T2DM) skeletal muscle, this study analysed the adaptive expression of genes involved in fatty acid (FA) oxidation and mitochondrial biogenesis in primary myotubes treated with elevated FAs. METHODS: Muscle samples from obese or obese T2DM donors were stored or processed into human primary skeletal muscle myotubes, which were treated for 6 h with a saturated (palmitic acid) or a monounsaturated (oleic acid) FA with or without a polyunsaturated FA (eicosapentaenoic acid: EPA). Real-time PCR analysis was used to determine mRNA expression. RESULTS: Basal pyruvate dehydrogenase kinase 4 (PDK4) mRNA expression in whole muscle samples from obese and T2DM subjects was increased compared to lean (P < 0.05; n = 13-20/group). In obese- and T2DM-derived myotubes, oleic acid treatment alone and in combination with EPA increased PDK4 mRNA expression compared to control (P < 0.05; n = 7/group), whereas palmitic acid alone and in combination with EPA only increased PDK4 mRNA in T2DM-derived myotubes compared to control (P < 0.05; n = 7/group). EPA alone did not alter mRNA expression of PDK4. CONCLUSIONS: These findings show that FAs induce the expression of PDK4 mRNA, which was increased in myotubes cultured from obese and T2DM donors. This persistent difference in PDK4 expression, present after culturing, suggests a fundamental alteration in the FA-mediated gene expression. This may in turn translate to differences in the regulation of oxidative substrate flux to impact on insulin sensitivity.

Brown adipocyte progenitor population is modified in obese and diabetic skeletal muscle.

Brown adipose tissue mitochondria express the unique thermogenic uncoupling protein-1. Recently, brown adipocyte progenitors have been identified in the CD34+ cell population of human skeletal muscle. The aims of this study were firstly to determine if obesity and diabetes have altered amounts of muscle brown adipocyte progenitors and, secondly, to establish if the latter are correlated with clinical parameters of obesity and diabetes. Body mass index (BMI), plasma glucose, insulin, cholesterol and triglycerides as well as homeostasis model assessment were measured in lean (n=10), obese (n=18) and obese-diabetic (n=15) subjects and muscle biopsies were taken from the rectus abdominus. CD34 being also expressed on endothelial cells, we measured CD31, another endothelial marker, and expressed the brown adipocyte progenitors, as the CD34/CD31 mRNA ratio. The latter was significantly reduced in the obese vs lean subjects suggesting a smaller pool of brown adipocyte progenitors. More strikingly, for lean and obese subjects negative correlations were observed between the CD34/CD31 mRNA ratios and BMI, fasting insulin levels and homeostasis model assessment. These correlations highlight the potential physiological relevance of the muscle CD34/CD31 mRNA ratio.

Microvascular architecture of experimental colon tumors in the rat.

Tumor cell proliferation is dependent upon concurrent growth of a supporting vasculature. This study aims to characterize the structural features of the microvasculature within a primary tumor model. There were 22 colon tumors induced in 16 rats by repeated administration of dimethylhydrazine. A cast of the microvessels was prepared by intraarterial administration of acrylic resin (Mercox). After corrosion of the tissue, the cast was examined by scanning electron microscopy. Tumors 2.6 to 12.0 mm in diameter were examined. Within polypoid carcinomas up to 5.7 mm in diameter, there were two distinct vascular zones, a luminal vascular zone continuous with the vasculature of normal mucosa and a central zone continuous with the normal submucosa and muscularis propria vessels. Within both vascular zones, the organization of microvessels had the same general pattern as in normal mucosa. However, in tumors with diameters greater than 5.7 mm, the vasculature was seen to be disorganized and of a greater density than normal. In the smallest tumors, few morphological changes were seen in the individual microvessels when compared to normal. However, with tumor growth, there was elongation and increased diameters of the microvessels within the tumor. Microvessels within the luminal zone of the tumors which could definitely be traced to veins had diameters of 50 to 100 microns (compared to 12 to 30 microns for normal venules). Individual microvessels varied in diameter along their course forming saccular dilations in places. Networks of frequently anastomosing microvessels were formed. Extravasation of resin occurred from some microvessels. Elongated vessels of uniform diameter which travel distances up to 2 mm without branching were seen and were probably arterioles. These appearances indicate that there are two distinct stages of development of the vasculature within primary tumors, an early phase where the tumor is supplied by the preexisting host microvessels, followed by a phase of proliferation of new vessels with abnormal morphological characteristics.

Combretastatin A4 prodrug study of effect on the growth and the microvasculature of colorectal liver metastases in a murine model.

Combretastatin A4P (CA4P) is a prodrug that, in active form, binds to tubulin microtubules of capillary endothelial cells. Studies to date indicate it has significant activity as a specific tumor vascular targeting agent. The goals were to assess the effects of CA4P on tumor growth and microvasculature of colorectal liver metastases in the mouse model, using stereological and histological methods to measure tumor growth, and vascular corrosion casting and laser doppler flowmetry to assess effect on the microvasculature. Continuous s.c. infusion of CA4P produced a major reduction in tumor growth. The percentage of the liver occupied by metastases decreased from 20.55 +/- 13.3% in controls to 7.46 +/- 5.99% in treated animals (P = 0.03). Ultrastructural study of tumor microvasculature after a single dose of CA4P revealed marked effects 1 h after treatment. There was loss of patent microvessels at the normal liver-tumor interface. Central microvascular density was reduced, with constriction and tapering of vessels. CA4P appeared to cause no damage to normal liver tissue or vasculature. Tumor blood flow decreased from 37.6 +/- 13.9% in controls to 24.4 +/- 6.1% in tumors >5 mm in diameter, 1 h after treatment with CA4P (P < 0.03). Quantitative histology of tissue at 6 and 24 h after CA4P treatment showed a significant increase in tumor necrosis (48.7 +/- 21% and 55.5 +/- 19% compared with controls, 20.6 +/- 8%; P = 0.01). Continuous infusion with CA4P causes marked reduction in tumor volume. A single dose of CA4P causes major changes of the tumor microvasculature, reduction of tumor blood flow, and increase in tumor necrosis. CA4P has a potential role in the management of patients with liver metastases.

Sleep disturbance and obesity: changes following surgically induced weight loss.

BACKGROUND: Obesity causes sleep disturbance and is the most significant risk factor for sleep apnea. Only surgical methods provide substantial sustained weight loss for most severely obese subjects. OBJECTIVE: To study sleep disturbance in patients undergoing laparoscopic adjustable gastric banding with a commercially available product (Lap-Band). METHODS: In this study, 313 consecutive patients with severe obesity (body mass index [calculated as weight in kilograms divided by the square of height in meters] >35) completed a preoperative sleep questionnaire and clinical assessment. One hundred twenty-three patients completed the same assessment 12 months after surgery. The characteristics of sleep disturbance and changes in responses to weight loss have been assessed. RESULTS: There was a high prevalence of significantly disturbed sleep in men (59%) and women (45%), with women less likely to have had their sleep disturbance investigated. Observed sleep apnea was more common in men, but daytime sleepiness was not affected by sex. Waist circumference was the best clinical measure predicting observed sleep apnea (R = 0.36; P<.001). The group lost an average of 48% (SD, 16%) of excess weight by 12 months. There was a significant improvement in the responses to all questions at follow-up, with habitual snoring reduced to 14% (preoperative value, 82%), observed sleep apnea to 2% (preoperative value, 33%), abnormal daytime sleepiness to 4% (preoperative value, 39%), and poor sleep quality to 2% (preoperative value, 39%) (P<.001 for all). CONCLUSIONS: Obesity-related sleep disorders improve markedly with weight loss. Sustainable weight loss should be a primary aim in the management of severely obese patients with significant sleep disturbance, including sleep apnea. Low-risk laparoscopic obesity surgery should be considered for selected patients with this important comorbidity.

Gastroesophageal reflux in obesity: the effect of lap-band placement.

BACKGROUND: Gastroesophageal reflux disease (GERD) is a common condition which is often aggravated by morbid obesity. Lap-Band surgery provides effective weight loss in the morbidly obese. There have been several reports that gastric banding causes or aggravates reflux. The aim of this study was to evaluate the effect of Lap-Band placement on GERD. METHODS: All patients with a significant history of GERD who had a Lap-Band inserted over a 2-year period were evaluated postoperatively to assess any change in impact on reflux. Resolution required absence of reflux symptoms and no anti-reflux drug therapy. RESULTS: There were 48 (16%) of 274 consecutive patients with a significant history of reflux esophagitis requiring regular therapy preoperatively. The median age was 39 (range 23-58) and M:F ratio was 5:43. We confirm a high prevalence of GERD in patients with morbid obesity: 17% with symptoms requiring regular therapy (Community Norm 7%). Total resolution of all reflux symptoms occurred in 36 (76%) patients, improvement in 7 (14%), no change in 3 (6%), and aggravation of symptoms in 2 (4%). Patients with severe and moderate symptoms had similar improvement. Resolution or improvement was reported soon after surgery. CONCLUSION: Rapid and major improvement in symptoms of GERD occurs after Lap-Band placement. The placement of the band probably acts directly to reduce reflux. This result contrasts with reports which have found gastric banding causes or aggravates GERD.

Pre-operative predictors of weight loss at 1-year after Lap-Band surgery.

BACKGROUND: The authors studied a range of preoperative factors for their predictive value of effectiveness of Lap-Band placement, using the percentage of excess weight loss at 1-year as the outcome measure (%EWL1). METHODS: All factors were measured and recorded prior to surgery. Factors included: patient demographics, family, medical and weight history. Laboratory measures and the responses to the SF-36 Health Survey were also assessed. Factors were assessed for correlation with %EWL1. RESULTS: The group (N=440, F:M 383:57) had mean age 40.0+/-9.5 years, weight of 126+/-25 kg, and BMI 45.6+/-7.5 kg/m2 pre-operatively. At 1-year follow-up, the group had mean weight 97.6< or =20 kg, BMI 35.6 = 6.3 kg/m2, and %EWL1 45.8< or =17%. Increasing age (R= -0.13, p<0.01) and preoperative BMI (R=-0.22, p<0.001) were significantly associated with less %EWL1 and all other factors were controlled for these before assessing significance. Important factors associated with a lower %EWL1 included: hyperinsulinemia (R=-0.36, p<0.001), insulin resistance (R=-0.33, p<0.001) and disease associated with insulin resistance, poor physical ability, pain, and poor general health responses to the SF-36 Health Survey. Patients who consumed alcohol regularly had a better rate of weight loss (R= 0.23, p<0.005). Factors that had no influence included gender, a history of mental illness and measures of mental health, previous bariatric surgery, and a history of many medical conditions associated with obesity. CONCLUSION: Important physical factors have been found to influence the rate of weight loss. Those with increased age, pain, physical disability and insulin resistance have a great deal to gain from weight loss. Although this study has identified factors that are associated with less weight loss, we have not found any factor that predicts an unacceptably low weight loss and thus provides a contraindication to Lap-Band placement. The findings of this study allow us to set more realistic goals for the rate of weight loss in specified sub-groups of our patients.

Pregnancy after Lap-Band surgery: management of the band to achieve healthy weight outcomes.

BACKGROUND: Severely obese women have higher obstetric risks and poorer neonatal outcomes. Weight loss reduces obstetric risk. The introduction of a laparoscopically-placed adjustable gastric band, a safe and effective method of weight loss, has given us the ability and responsibility to adjust the band in relation to pregnancy. OBJECTIVE: Our aim was to devise a safe management plan to achieve healthy maternal weight gain (Institute of Medicine 1990) during pregnancy. METHODS: In a cohort group of 650 patients to have a Lap-Band placement for severe obesity, we have reviewed the management of the band and pregnancy outcomes of all women (n=20) to complete a pregnancy (n=22) with a band in-situ. RESULTS: All 22 pregnancies were singleton, with no primary caesarean sections (3 for recurring indications). The mean maternal weight gain was 8.3 kg compared with 15.2 kg for the 15 previous pregnancies of women in this group (p<0.05). There was no difference in birth weights. Obstetric complications were minimal, and there were no premature or low birth weight infants. 11 of 15 subjects with active management of the band achieved a maternal weight gain within the advised range compared with only 2 of 7 prior to this. CONCLUSION: The ability to adjust gastric restriction allows optimal control of maternal weight change in pregnancy and should help avoid the risks of excessive weight change.

Sulindac inhibits the rate of growth and appearance of colon tumors in the rat.

Sulindac (cis-5-fluoro-2-methyl-1-[p-(methylsulfinyl) benzylidene] indene-3-acetic acid), an inhibitor of prostaglandin synthesis, has been reported to cause regression of colon polyps in patients with familial polyposis coli and Gardner's syndrome. We examined the effect of sulindac on the growth of primary colon carcinomas in rats. Colon tumors were induced in 18 rats by repeated subcutaneous administration of dimethylhydrazine. The site and diameter of each tumor were measured via laparotomy and colonoscopy. Rats were randomized to receive either sulindac (10 mg/kg) twice daily or vehicle (0.5% methylcellulose). After 4 weeks of treatment, the site and size of tumors in the colon were again recorded. In eight rats receiving sulindac, no new tumors were identified, while in 10 control rats, 13 additional tumors were found after treatment. There was a significantly greater increase in size of the tumors in the control group (56.4 mm for 26 tumors) compared with the rats receiving sulindac (9.3 mm for 14 tumors). We report that sulindac inhibits the rate of development and the rate of growth of colon tumors in the rat.

A multicenter trial for resuscitation of injured patients with 7.5% sodium chloride. The effect of added dextran 70. The Multicenter Group for the Study of Hypertonic Saline in Trauma Patients.

OBJECTIVE: To evaluate the use of 250 mL of a 7.5% sodium chloride solution, both with and without added dextran 70, for the prehospital resuscitation of hypotensive trauma patients. DESIGN: Double-blind randomized trial. SETTING: Six trauma systems served by helicopter transport. PATIENTS: Injured patients with systolic blood pressures less than 90 mm Hg at any time in the field or during helicopter transport. INTERVENTIONS: Infusion of study solution, in the field or during transport, followed by conventional isotonic solutions as needed. Solutions studied in four cohorts were as follows: (1) lactated Ringer's; (2) 7.5% sodium chloride (hypertonic saline); (3) 7.5% sodium chloride combined with 6% dextran 70; and (4) 7.5% sodium chloride combined with 12% dextran 70. MAIN OUTCOME MEASURES: Blood pressure response; survival to time of hospital discharge among the treatment groups; and survival compared with that predicted by norms from the Major Trauma Outcome Study (MTOS). RESULTS: The mean (+/- SD) change in systolic blood pressure on arrival in the emergency department was significantly higher in the hypertonic saline solution group than that in the lactated Ringer's solution group (34 +/- 46 vs 11 +/- 49 mm Hg, P < .03). Overall survival in the four treatment groups was 49%, 60%, 56%, and 45% (not statistically significant). Survival in the hypertonic saline solution group, however, was significantly higher than that predicted by the MTOS norms (60% vs 48%, P < .001). Survival to hospital discharge in patients with baseline Glasgow Coma Scale scores of 8 or less was correlated with treatment group (P < .05 by logistic regression and P < .01 by Cox proportional-hazards analysis; with survival in the hypertonic saline solution group [34%] vs lactated Ringer's solution group [12%]). CONCLUSIONS: Prehospital infusion of 250 mL of 7.5% sodium chloride is associated with an increase in blood pressure and an increase in survival to hospital discharge compared with survival predicted by the MTOS norms. Patients with low baseline Glasgow Coma Scale scores seem to benefit the most from 7.5% sodium chloride resuscitation. Hypertonic saline solution without added dextran 70 is as effective as the more expensive solutions that contain dextran 70.

Reduced plasma homocysteine in obese red wine consumers: a potential contributor to reduced cardiovascular risk status.

BACKGROUND: Moderate alcohol consumption is associated with improved vascular risk profile and decreased mortality in the middle aged. An elevated homocysteine concentration is an independent risk factor for cardiovascular disease. OBJECTIVE: To examine the relationship between alcohol consumption and homocysteine concentrations in severely obese patients (body mass index (BMI)>35). DESIGN: A careful alcohol history was obtained from 350 (male:female 1:5) consecutive patients as part of preoperative assessment for surgical treatment of obesity. Data were obtained concerning amount, frequency, timing and type of alcohol consumption. Fasting homocysteine, serum folate and vitamin B(12) concentrations were measured. Differences between groups were assessed using Student t-test, and ANOVA. Linear regression was used to assess factors influencing homocysteine concentration. RESULTS: There is a U-shaped relationship between alcohol consumption and homocysteine concentrations, with light to moderate consumption being associated with lower concentrations. Those consuming <100 g/week (n=165) of alcohol had geometric mean (95% CI of mean) serum homocysteine concentrations of 8.5 (8.2-8.9) micromol/l compared with 9.5 (9.1-9.9) micromol/l for non or rare consumers (n=153; P=0.001). The lower concentrations of homocysteine in regular consumers were associated with higher folate concentrations of 9.4 (8.6-10.2) ng/ml when compared with non-consumers 7.5 (7.1-7.8) ng/ml (P=0.001). Red wine consumers (n=42) had lower fasting concentrations of homocysteine 7.8 (7.5-8.1) micromol/l compared with 153 non-consumers 9.4 (9.0-9.8) micromol/l (P<0.001), 82 beer and spirit consumers 9.0 (8.4-9.7) micromol/l (P=0.005) and 73 white wine consumers 8.8 (8.2-9.4 micromol/l (P=0.013). Red wine consumption was an independent predictor for lower homocysteine concentrations. CONCLUSION: Mild to moderate alcohol consumption, especially red wine consumption, in obese subjects is associated with lower fasting homocysteine concentrations. This may reduce cardiovascular risk and help explain the 'French paradox'.

Body composition changes following laparoscopic gastric banding for morbid obesity.

Most reports of outcome following obesity surgery report weight and co-morbidity changes only. We studied body composition changes in 17 adult patients (15 F, 2 M, age 43+/-2 years, range 28-58 years), with morbid obesity (initial BMI 40.4+/-4.9 kg/m(2), range 34.7-48.8) who were managed surgically by laparoscopically inserting an adjustable gastric band. Body composition was studied before and after surgery (mean interval of 909+/-51 days, range 441-1155 days) using anthropometry (abdominal circumference, AC, sum of four skinfold thicknesses, SFSUM), whole-body potassium counting (TBK), in vivo neutron activation analysis total body nitrogen (TBProtein) and whole-body dual-energy ray absorptiometry (total body percent fat TBF%, and total body bone mineral density TBBMD). Weight loss over the study period was 23.4+/-2.5 kg. ( p<0.0003) with an AC reduction of 20.0+/-4.5 cm ( p<0.008). Both SFSUM and TBF% were significantly reduced ( p<0.02 and p<0.0005 respectively). Both TBK and TBProtein after normalization for sex and height, were significantly ( p<0.0054 and p<0.001 respectively) reduced, but the ratio of loss of fat mass to fat-free mass, at 4.4:1 was usual for weight loss, and there was no significant changes in the ratio of potassium to protein. TBBMD, after normalization relative to a young same sex adult, was not significantly changed. In this group of patients, most of the substantial weight loss over a 2- to 3-year period was due to loss of fat mass, with relatively less reduction in the components of fat-free mass. Adjustable laparoscopic gastric banding induces fat loss without significant other deleterious effects on body composition.

Axis I disorders in adjustable gastric band patients: the relationship between psychopathology and weight loss.

BACKGROUND: Bariatric surgery candidates have higher rates of co-morbid psychological illnesses than those in the general population. The effect of weight loss on these illnesses is unclear. METHODS: This prospective observational study explored psychiatric co-morbidities and weight loss outcomes in 204 gastric banding surgery candidates. Psychiatric co-morbidities were assessed prior to surgery and 2 years post-surgery. One hundred and fifty patients (74%) completed assessments at both time points. RESULTS: At baseline, 39.7% of the patients met the criteria for a current axis I disorder as defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV). Mood disorders were the most frequent (26.5%), followed by anxiety disorders (15.2%) and binge eating disorder (13.2%). Preoperative psychopathology predicted clinical psychopathology at 2 years. No preoperative or post-operative axis I disorder was significantly related to weight loss at 2 years. The frequency of current axis I disorders decreased significantly from 39.7% preoperatively to 20% 2 years post-surgery. CONCLUSIONS: The point prevalence of psychopathology in this sample of Australian bariatric candidates is high. Psychopathology, preoperatively and at 2 years of follow-up, was not associated with weight loss at 2 years.

GPR119 regulates genetic markers of fatty acid oxidation in cultured skeletal muscle myotubes.

Gene knockout and agonist studies indicate that activation of the G protein-coupled receptor, GPR119, protects against diet-induced obesity and insulin resistance. It is not known if GPR119 activation in skeletal muscle mediates these effects. To address this uncertainty, we measured GPR119 expression in skeletal muscle and determined the effects of PSN632408, a GPR119 agonist, on the expression of genes and proteins required for fatty acid and glucose oxidation in cultured myotubes. GPR119 expression was readily detected in rat skeletal muscle and mRNAs were induced by 12 weeks of high-fat feeding. Treatment of cultured mouse C2C12 myotubes with 5 µM PSN632408 or 0.5 mM palmitate reduced expression of mRNAs encoding fatty acid oxidation genes to similar extents. More so, treatment with PSN632408 decreased AMPKα (Thr172 phosphorylation) activity in the absence of palmitate and ACC (Ser79 phosphorylation) activity in the presence of palmitate. In human primary myotubes PSN632408 decreased expression of PDK4 and AMPKα2 mRNA in myotubes derived from obese donors. These data suggest GPR119 activation in skeletal muscle may impair fatty acid and glucose oxidation.

Night eating syndrome and nocturnal snacking: association with obesity, binge eating and psychological distress.

OBJECTIVE: Night eating syndrome (NES) is characterized by a time-delayed pattern of eating relative to sleep, where most food is consumed in the evening and night. This study aimed to investigate the clinical significance of NES and nocturnal snacking by exploring the relationship between NES and (1) obesity, (2) binge eating disorder (BED) and (3) psychological distress. SUBJECTS: One hundred and eighty bariatric surgery candidates, 93 members of a non-surgical weight loss support group and 158 general community respondents (81 males/350 females, mean age: 45.8+/-13.3 years, mean body mass index (BMI): 34.8+/-10.8 and BMI range: 17.7-66.7). METHODS: NES diagnosis required within the previous 3 months: (1) no appetite for breakfast, (2) consumption of > or =50% of daily energy after 1900 hours and (3) sleep difficulties > or =3 nights/week. Nocturnal snacking (awakening to eat) was recorded. Validated questionnaires assessed BED, symptoms of depression, appearance dissatisfaction (AD) and mental health-related quality of life (MHQoL). NES and binge eating (BE) (> or =1 episode/week) were confirmed by interview. RESULTS: NES criteria were met by 11.1% of the total cohort. Across all groups, BE (P=0.001), BMI (P=0.003) and male gender (P=0.013) explained 10% of NES variance. Individuals with co-morbid NES and BE reported similarly elevated psychological distress as other binge eaters. NES alone was not associated with psychological distress. Those with NES who consumed nocturnal snacks reported poorer MHQoL (P=0.007) and greater depressive symptoms (P=0.039) and hunger (P=0.013) than others with NES. Low MHQoL (P=0.007) and male gender (P=0.022) explained 27% of the variance in the nocturnal snacking group. DISCUSSION: In this study, NES was positively associated with BMI, BE and male gender. Elevated psychological distress was only apparent in those who consumed nocturnal snacks. Further characterization and understanding of the clinical significance of NES and nocturnal snacking is required.

Changes in fat-free mass during significant weight loss: a systematic review.

OBJECTIVE: To identify the proportion of weight lost as fat-free mass (FFM) by various weight loss interventions. METHODS: Medline and Embase were systematically searched for reliable measurements of FFM before and after weight loss of >10 kg and eligible data were pooled. In a fixed effect model of % FFM loss/weight loss (%FFML), linear regression analysis was used to determine the influence of degree of caloric restriction, exercise, magnitude of weight loss, initial body mass index (BMI) and type of surgery. RESULTS: Data were included from 26 cohorts treated with dietary and behavioral interventions and 29 cohorts of bariatric surgery patients. The degree of caloric restriction was positively associated with %FFML (r (2)=0.31, P=0.006) and in three randomized controlled trials exercise was shown to decrease %FFML. Compared with laparoscopic adjustable gastric banding (LAGB), biliopancreatic diversion (BPD) and roux en Y gastric bypass (RYGB) caused greater log(e) (natural log) %FFML (r (2)=0.453, P<0.001). Differences in log(e) %FFML between surgical procedures were independent of initial BMI and magnitude of weight loss. CONCLUSIONS: The degree of caloric restriction, exercise and rate of weight loss influence the proportion of weight lost as FFM after non-surgical interventions. For surgical interventions, BPD and RYGB result in greater %FFML than LAGB.