Mechanisms underlying the efficacy of a rodent model of vertical sleeve gastrectomy - A focus on energy expenditure.

OBJECTIVE: Bariatric surgery remains the only effective and durable treatment option for morbid obesity. Vertical Sleeve Gastrectomy (VSG) is currently the most widely performed of these surgeries primarily because of its proven efficacy in generating rapid onset weight loss, improved glucose regulation and reduced mortality compared with other invasive procedures. VSG is associated with reduced appetite, however, the relative importance of energy expenditure to VSG-induced weight loss and changes in glucose regulation, particularly that in brown adipose tissue (BAT), remains unclear. The aim of this study was to investigate the role of BAT thermogenesis in the efficacy of VSG in a rodent model. METHODS: Diet-induced obese male Sprague-Dawley rats were either sham-operated, underwent VSG surgery or were pair-fed to the food consumed by the VSG group. Rats were also implanted with biotelemetry devices between the interscapular lobes of BAT to assess local changes in BAT temperature as a surrogate measure of thermogenic activity. Metabolic parameters including food intake, body weight and changes in body composition were assessed. To further elucidate the contribution of energy expenditure via BAT thermogenesis to VSG-induced weight loss, a separate cohort of chow-fed rats underwent complete excision of the interscapular BAT (iBAT lipectomy) or chemical denervation using 6-hydroxydopamine (6-OHDA). To localize glucose uptake in specific tissues, an oral glucose tolerance test was combined with an intraperitoneal injection of 14C-2-deoxy-d-glucose (14C-2DG). Transneuronal viral tracing was used to identify 1) sensory neurons directed to the stomach or small intestine (H129-RFP) or 2) chains of polysynaptically linked neurons directed to BAT (PRV-GFP) in the same animals. RESULTS: Following VSG, there was a rapid reduction in body weight that was associated with reduced food intake, elevated BAT temperature and improved glucose regulation. Rats that underwent VSG had elevated glucose uptake into BAT compared to sham operated animals as well as elevated gene markers related to increased BAT activity (Ucp1, Dio2, Cpt1b, Cox8b, Ppargc) and markers of increased browning of white fat (Ucp1, Dio2, Cited1, Tbx1, Tnfrs9). Both iBAT lipectomy and 6-OHDA treatment significantly attenuated the impact of VSG on changes in body weight and adiposity in chow-fed animals. In addition, surgical excision of iBAT following VSG significantly reversed VSG-mediated improvements in glucose tolerance, an effect that was independent of circulating insulin levels. Viral tracing studies highlighted a patent neural link between the gut and BAT that included groups of premotor BAT-directed neurons in the dorsal raphe and raphe pallidus. CONCLUSIONS: Collectively, these data support a role for BAT in mediating the metabolic sequelae following VSG surgery, particularly the improvement in glucose regulation, and highlight the need to better understand the contribution from this tissue in human patients.

A fibre-coupled UHV-compatible variable angle reflection-absorption UV/visible spectrometer.

We present a novel UV/visible reflection-absorption spectrometer for determining the refractive index, n, and thicknesses, d, of ice films. Knowledge of the refractive index of these films is of particular relevance to the astrochemical community, where they can be used to model radiative transfer and spectra of various regions of space. In order to make these models more accurate, values of n need to be recorded under astronomically relevant conditions, that is, under ultra-high vacuum (UHV) and cryogenic cooling. Several design considerations were taken into account to allow UHV compatibility combined with ease of use. The key design feature is a stainless steel rhombus coupled to an external linear drive (z-shift) allowing a variable reflection geometry to be achieved, which is necessary for our analysis. Test data for amorphous benzene ice are presented as a proof of concept, the film thickness, d, was found to vary linearly with surface exposure, and a value for n of 1.43 ± 0.07 was determined.

Systematic review and meta-analysis: non-invasive detection of non-alcoholic fatty liver disease related fibrosis in the obese.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a significant disease burden in obesity. Liver fibrosis is an important prognostic factor in NAFLD, and detection is vital. The pathophysiological changes of obesity can alter the accuracy of non-invasive NAFLD tests. We aimed to review current evidence for common non-invasive tests for NAFLD-related fibrosis in obesity. METHODS: We systematically searched for studies assessing the diagnostic accuracy of 11 biomarker panels and elastography techniques for NAFLD-related fibrosis in obesity. Meta-analyses were performed where possible. RESULTS: Thirty-eight studies were identified assessing the selected tests in obese populations. Simple biomarker panels (e.g. NAFLD fibrosis score) were the most validated. Evidence showed better accuracy of complex biomarker panels (NAFLD fibrosis score: summary receiver operator characteristic [SROC] 0.795-0.813 vs. enhanced liver fibrosis: SROC 0.962); however, these were poorly validated in obesity. Elastography techniques were better studied and had high diagnostic accuracy (transient elastography: SROC 0.859; magnetic resonance elastography: SROC 0.965) but were limited by BMI-dependent failure. Limited evidence was found to validate the accuracy of any test in exclusively obese populations. CONCLUSION: In obese subjects, complex biomarker panels and elastography have been reasonable to good accuracy for NAFLD-related fibrosis; however, these methods have not been well validated. Further study in this high-risk population is needed.

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.

Albert Edwin William (LOMA) Miles (1912-2008) extracts from personal letters on dental matters.

Professor Miles (1912-2008) was a key player establishing dentistry as an academic subject. In the many letters he wrote to Helen Liversidge and me, he describes his involvement as Hon. Curator of the Odontological Museum, Editor Archives of Oral Biology, Assistant scientific editor of the BDJ. He writes about his association with Robert Maxwell and the Pergamon Press and his interests and friendships.

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.

Neural and humoral changes associated with the adjustable gastric band: insights from a rodent model.

BACKGROUND: Bariatric surgical procedures, including the laparoscopic adjustable gastric band (LAGB), are currently the only effective treatments for morbid obesity, however, there is no clear understanding of the mechanisms underpinning the efficacy of LAGB. The aim of this study is to examine changes in activation of the sensory neuronal pathways and levels of circulating gut hormones associated with inflation of an AGB. DESIGN AND RESULTS: The trajectory within the central nervous system of polysynaptic projections of sensory neurons innervating the stomach was determined using the transsynaptically transported herpes simplex virus (HSV). Populations of HSV-infected neurons were present in the brainstem, hypothalamus and cortical regions associated with energy balance. An elevation of Fos protein was present within the nucleus of the solitary tract, a region of the brainstem involved in the control of food intake, following acute and chronic band inflation. Two approaches were used to test (1) the impact of inflation of the band alone (on a standard caloric background) or (2) the impact of a standard caloric meal (on the background of the inflated band) on circulating gut hormones. Importantly, there was a significant elevation of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) following oral gavage of a liquid meal in animals with pre-inflated bands. There was no impact of inflation of the band alone on circulating GLP-1, PYY or ghrelin in animals on a standard caloric background. CONCLUSION: These data are consistent with the notion that the LAGB exerts its effects on satiety, reduced food intake and reduced body weight by the modulation of both neural and hormonal responses with the latter involving an elevation of meal-related levels of GLP-1 and PYY. These data are contrary to the view that the surgery is purely 'restrictive'.

The mechanism of weight loss with laparoscopic adjustable gastric banding: induction of satiety not restriction.

Laparoscopic adjustable gastric banding (LAGB) has rapidly emerged as a popular bariatric procedure because of its safety, efficacy, durability and adjustability. Despite widespread use, there is limited understanding of how it induces weight loss. Previously, it has been classified as a restrictive procedure, physically limiting the patient to a small meal that subsequently slowly empties into the distal stomach. However, the tiny pouch of stomach created above the LAGB appears to be unable to accommodate even the smallest of meals. Therefore, the key mechanism has been hypothesized to be the induction of satiety via, as yet, undefined pathways. The critical question remains: what are the key physiological changes that lead to satiety and weight loss? In successful LAGB patients, a consistent intraluminal pressure at the level of the LAGB of 26.9 ± 19.8 mm Hg is observed. Studies using semi-solid swallows combined with intraluminal pressure recordings have demonstrated that semi-solid transit across the resistance of the LAGB is mediated by repeated esophageal peristaltic contractions (mean 4.5 ± 2.9) that produce episodic flow, interspersed by reflux events. Failed transit results in obstruction and regurgitation, whereas dilatation of the supraband stomach induces severe and intolerable reflux. Overall gastric emptying does not appear to be significantly altered following LAGB. Focused investigations have shown that the supraband stomach is empty of an ingested meal 1-2 min after intake ceases. Considerable progress has been made in understanding the mechanical physiological effects of the LAGB on esophageal and proximal gastric function. These have been correlated with patient outcomes and sensations. On the basis of recent data, it appears that the LAGB activates the peripheral satiety mechanism without physically restricting the meal size. Therefore, it should not be classified as a restrictive procedure. The precise mechanism of weight loss with the LAGB remains to be delineated.

A rodent model of adjustable gastric band surgery-implications for the understanding of underlying mechanisms.

BACKGROUND: Bariatric surgery is currently the only anti-obesity therapy that can deliver weight loss of up to 20-30% of body weight. Laparoscopic adjustable gastric banding (LAGB) and Roux-en-y gastric bypass are the most commonly performed of these surgeries. The mechanisms by which LAGB initiates an increase in satiety remain completely unknown. The aim of this study is to establish a rodent model of adjustable gastric banding (AGB) that will enable investigation of these mechanisms. METHODS: Sprague-Dawley rats were implanted with adjustable gastric bands immediately below the gastro-esophageal junction around the glandular stomach. This band, as in humans, can be inflated via an exteriorized port resulting in an incremental impact on the stomach. RESULTS: Rats with an incremental inflation of the AGB showed a clear stepwise reduction in food intake and body weight. Normal food intake and body weight gain were restored with band deflation. Barium-assisted X-ray of the stomach showed the formation of a small gastric pouch proximal to the inflated band in a manner analogous to the human LAGB. CONCLUSIONS: This is the first animal model of the AGB that allows incremental inflation for optimal tightening of the band in the conscious animal with corresponding effects on food intake and body weight. This model will allow measurement of acute and chronic neural and hormonal changes following activation of the band in the conscious animal and will provide the potential to inform and improve surgical approaches that are at the forefront of obesity treatments.

The adsorption and desorption of ethanol ices from a model grain surface.

Reflection absorption infrared spectroscopy (RAIRS) and temperature programed desorption (TPD) have been used to probe the adsorption and desorption of ethanol on highly ordered pyrolytic graphite (HOPG) at 98 K. RAIR spectra for ethanol show that it forms physisorbed multilayers on the surface at 98 K. Annealing multilayer ethanol ices (exposures >50 L) beyond 120 K gives rise to a change in morphology before crystallization within the ice occurs. TPD shows that ethanol adsorbs and desorbs molecularly on the HOPG surface and shows four different species in desorption. At low coverage, desorption of monolayer ethanol is observed and is described by first-order kinetics. With increasing coverage, a second TPD peak is observed at a lower temperature, which is assigned to an ethanol bilayer. When the coverage is further increased, a second multilayer, less strongly bound to the underlying ethanol ice film, is observed. This peak dominates the TPD spectra with increasing coverage and is characterized by fractional-order kinetics and a desorption energy of 56.3+/-1.7 kJ mol(-1). At exposures exceeding 50 L, formation of crystalline ethanol is also observed as a high temperature shoulder on the TPD spectrum at 160 K.

Treatment response in melancholia.

OBJECTIVE: Ascertain the response to specific depression treatments in melancholic and non-melancholic depressed patients. METHOD: Literature review focusing on studies addressing symptoms, diagnostic profiles, severity and other predictors of outcome with antidepressant medication, electroconvulsive therapy (ECT), psychotherapy and placebo. RESULTS: Patients with melancholia do not consistently differ from those with non-melancholic depression in their response to antidepressants and ECT, but patients with melancholia show a significantly lower rate of placebo response. Depressed patients classified as severely ill-many of whom are melancholic-likewise do not differ from the less severely ill in response to antidepressants but do have a consistently lower placebo response rate. The little available data from psychotherapy studies also consistently show that melancholic and severely depressed patients are less likely than the more mildly depressed to improve with various types of psychotherapy. Depressed patients with increased pituitary-adrenocortical activity-most of whom are melancholic-show a similar pattern of treatment response: they do well with ECT and antidepressants and poorly with placebo and psychotherapies. CONCLUSION: The research data, in the aggregate, suggest that the presence of melancholia predicts a poor response to psychotherapy and placebo and a relatively good response to antidepressants and ECT.

Reflection absorption infrared spectroscopy and temperature programmed desorption investigations of the interaction of methanol with a graphite surface.

Reflection absorption infrared spectroscopy (RAIRS) and temperature programmed desorption (TPD) have been used to investigate the adsorption of methanol (CH(3)OH) on the highly oriented pyrolytic graphite (HOPG) surface. RAIRS shows that CH(3)OH is physisorbed at all exposures and that crystalline CH(3)OH can be formed, provided that the surface temperature and coverage are high enough. It is not possible to distinguish CH(3)OH that is closely associated with the HOPG surface from CH(3)OH adsorbed in multilayers using RAIRS. In contrast, TPD data show three peaks for the desorption of CH(3)OH. Initial adsorption leads to the observation of a peak assigned to the desorption of a monolayer. Subsequent adsorption leads to the formation of multilayers on the surface and two TPD peaks are observed which can be assigned to the desorption of multilayer CH(3)OH. The first of these shows a fractional order desorption, assigned to the presence of hydrogen bonding in the overlayer. The higher temperature multilayer desorption peak is only observed following very high exposures of CH(3)OH to the surface and can be assigned to the desorption of crystalline CH(3)OH.

Hydrolysis of lactose in whey permeate for subsequent fermentation to ethanol.

Fermentation of lactose in whey permeate directly into ethanol has had only limited commercial success, as the yields and alcohol tolerances of the organisms capable of directly fermenting lactose are low. This study proposes an alternative strategy: treat the permeate with acid to liberate monomeric sugars that are readily fermented into ethanol. We identified optimum hydrolysis conditions that yield mostly monomeric sugars and limit formation of fermentation inhibitors such as hydroxymethyl furfural by caramelization reactions. Both lactose solutions and commercial whey permeates were hydrolyzed using inorganic acids and carbonic acid. In all cases, more glucose was consumed by secondary reactions than galactose. Galactose was recovered in approximately stoichiometric proportions. Whey permeate has substantial buffering capacity-even at high partial pressures (>5500 kPa[g]), carbon dioxide had little effect on the pH in whey permeate solutions. The elevated temperatures required for hydrolysis with CO2-generated inhibitory compounds through caramelization reactions. For these reasons, carbon dioxide was not a feasible acidulant. With mineral acids reversion reactions dominated, resulting in a stable amount of glucose released. However, the Maillard browning reactions also appeared to be involved. By applying Hammet's acidity function, kinetic data from all experiments were described by a single line. With concentrated inorganic acids, low reaction temperatures allowed lactose hydrolysis with minimal by-product formation and generated a hexose-rich solution amenable to fermentation.