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 ​± ​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 ​< ​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 ​< ​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 ​< ​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

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 oppor- tunity 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 longitu- dinal 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/m 2 ) who under- went 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 subcor- tical 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 in- crease 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 in- crease 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 along- side 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

Change in Brain Volume and Cortical Thickness after Behavioral and Surgical Weight Loss Intervention

Obesity is associated with reduced cortical thickness and brain volume, which may be related to poor nutrition. Given that brain atrophy in anorexia nervosa recovers with nutritional improvements and weight gain, it is worth examining how brain structure changes at the other end of the weight spectrum with weight loss. Thus, this study aimed to examine change in cortical thickness and brain volume in 47 patients with severe obesity who participated in no treatment, behavioral weight loss, or bariatric surgery. T1-weighted MRI scans were conducted pre-treatment and approximately four months later. Measures of cortical thickness, gray matter volume, and white matter volume were compared between time points. Despite overall reduction in BMI, there was no significant change in cortical thickness. There was a significant increase in left hemisphere gray matter and white matter volumes across the sample. At baseline and follow-up, there was no relationship between cortical thickness or brain volumes and BMI. This study is the first to examine changes in cortical thickness and brain volume with weight loss in adults with obesity and the findings show partial support for the hypotheses that weight loss results in increased cortical gray and white matter

Behavioural and neuroimaging studies of food reward after bariatric surgery for obesity

BACKGROUND Roux-en-Y gastric bypass (RYGB) surgery is the most effective treatment for obesity and has greater efficacy for weight loss than gastric banding (BAND) surgery. The superior weight loss seen after RYGB may result from profoundly different effects on food hedonics and reward brought about by physiological changes secondary to the distinct manipulations of gut anatomy. AIMS To compare body mass index (BMI) matched patients after RYGB or BAND surgery and unoperated controls using comprehensive phenotyping of brain structure and function, eating behaviour and metabolism. METHODS In these cross-sectional studies, un-operated controls and patients after RYGB and BAND surgery had functional and anatomical neuroimaging of food reward systems. Reward responses to food were assessed with a functional magnetic resonance imaging (fMRI) food picture evaluation task. Anatomical differences in grey and white matter were assessed using voxel-based morphometry (VBM) and diffusion tensor imaging (DTI). Eating behaviour, food appeal and palatability, potential mediators, and post-ingestive effects were compared between groups using questionnaires, test meals, food diaries and assay of plasma hormones and metabolites. Surgical patients were compared in both the fasted and fed state, and after administration of the somatostatin analogue, Octreotide, to suppress anorexigenic gut hormone responses after RYGB. RESULTS Obese patients after RYGB had healthier gut-brain-hedonic responses to food than patients after BAND surgery. RYGB patients had lower activation than BAND patients in brain reward systems, particularly to high-calorie foods, including the orbitofrontal cortex, amygdala, caudate nucleus, nucleus accumbens and hippocampus. This was associated with lower palatability and appeal of high-calorie foods, and healthier eating behaviour, including less fat intake, in RYGB compared to BAND patients and/or BMI-matched unoperated controls. These differences were not explicable by differences in hunger or psychological traits between the surgical groups, or by differences in brain structure as measured by VBM and DTI. However anorexigenic plasma gut hormones (GLP-1 and PYY), plasma bile acids and symptoms of dumping syndrome were increased in RYGB patients. Octreotide increased nucleus accumbens activation to food pictures, increased food appeal and decreased post-meal satiety in patients after RYGB, but not BAND surgery. The preliminary nature of this small study precludes extensive interpretation especially of the difference between surgical groups. Patients in the operated groups (RYGB and BAND) had lower grey matter density in areas involved in reward processing, including the amygdala, nucleus accumbens and hippocampus compared to BMI-matched controls. There was no difference between the groups in white matter tract integrity. CONCLUSIONS Identification of these differences in the gut-brain axis and hence food hedonic responses as a result of altered gut anatomy/physiology provides a novel explanation for the more favorable long-term weight loss seen after RYGB than BAND surgery. This supports targeting of gut-brain reward systems for future treatments of obesity.Open Acces

The distribution of ghrelin cells in the human and animal gastrointestinal tract: a review of the evidence

The growth hormone and appetite are regulated by a 28-peptide hormone called ghrelin, which is produced in the stomach, pituitary gland, and other body tissues. The physiological roles fulfilled by ghrelin include regulation of food intake, cardiac output, reproductive system, proliferation of cells, and formation of osteoblasts, as well as action against inflammation/fibrosis. The ghrelin present in the body can be distinguished as acylated ghrelin and deacylated ghrelin. Furthermore, both in humans and other animals, the entirety of the gastrointestinal tract comprises ghrelin cells, which are classified as open-type and closed-type cells. The present study reviews the evidence about how ghrelin cells are distributed in the human and the animal body

Association of obesity with disease outcome in multiple sclerosis

BackgroundObesity reportedly increases the risk for developing multiple sclerosis (MS), but little is known about its association with disability accumulation.MethodsThis nationwide longitudinal cohort study included 1066 individuals with newly diagnosed MS from the German National MS cohort. Expanded Disability Status Scale (EDSS) scores, relapse rates, MRI findings and choice of immunotherapy were compared at baseline and at years 2, 4 and 6 between obese (body mass index, BMI ≥30 kg/m2) and non-obese (BMI <30 kg/m2) patients and correlated with individual BMI values.ResultsPresence of obesity at disease onset was associated with higher disability at baseline and at 2, 4 and 6 years of follow-up (p<0.001). Median time to reach EDSS 3 was 0.99 years for patients with BMI ≥30 kg/m2 and 1.46 years for non-obese patients. Risk to reach EDSS 3 over 6 years was significantly increased in patients with BMI ≥30 kg/m2 compared with patients with BMI <30 kg/m2 after adjustment for sex, age, smoking (HR 1.87; 95% CI 1.3 to 2.6; log-rank test p<0.001) and independent of disease-modifying therapies. Obesity was not significantly associated with higher relapse rates, increased number of contrast-enhancing MRI lesions or higher MRI T2 lesion burden over 6 years of follow-up.ConclusionsObesity in newly diagnosed patients with MS is associated with higher disease severity and poorer outcome. Obesity management could improve clinical outcome of MS

Effects of bariatric surgery and dietary interventions for obesity on brain neurotransmitter systems and metabolism: A systematic review of positron emission tomography (PET) and single-photon emission computed tomography (SPECT) studies

This systematic review collates studies of dietary or bariatric surgery interventions for obesity using positron emission tomography and single-photon emission computed tomography. Of 604 publications identified, 22 met inclusion criteria. Twelve studies assessed bariatric surgery (seven gastric bypass, five gastric bypass/sleeve gastrectomy), and ten dietary interventions (six low-calorie diet, three very low-calorie diet, one prolonged fasting). Thirteen studies examined neurotransmitter systems (six used tracers for dopamine DRD2/3 receptors: two each for 11C-raclopride, 18F-fallypride, 123I-IBZM; one for dopamine transporter, 123I-FP-CIT; one used tracer for serotonin 5-HT2A receptor, 18F-altanserin; two used tracers for serotonin transporter, 11C-DASB or 123I-FP-CIT; two used tracer for μ-opioid receptor, 11C-carfentanil; one used tracer for noradrenaline transporter, 11C-MRB); seven studies assessed glucose uptake using 18F-fluorodeoxyglucose; four studies assessed regional cerebral blood flow using 15O-H2O (one study also used arterial spin labeling); and two studies measured fatty acid uptake using 18F-FTHA and one using 11C-palmitate. The review summarizes findings and correlations with clinical outcomes, eating behavior, and mechanistic mediators. The small number of studies using each tracer and intervention, lack of dietary intervention control groups in any surgical studies, heterogeneity in time since intervention and degree of weight loss, and small sample sizes hindered the drawing of robust conclusions across studies

Effects of Obesity and Weight Loss Following Bariatric Surgery on Brain Function, Structural Integrity and Metabolism

Obesity is one of the key challenges to health care system worldwide and its prevalence is estimated to rise to pandemic proportions. Numerous adverse health effects follow with increasing body weight, including increased risk of hypertension, diabetes, hypercholesterolemia, musculoskeletal pain and cancer. Current evidence suggests that obesity is associated with altered cerebral reward circuit functioning and decreased inhibitory control over appetitive food cues. Furthermore, obesity causes adverse shifts in metabolism and loss of structural integrity within the brain. Prior cross-sectional studies do not allow delineating which of these cerebral changes are recoverable after weight loss. We compared morbidly obese subjects with healthy controls to unravel brain changes associated with obesity. Bariatric surgery was used as an intervention to study which cerebral changes are recoverable after weight loss. In Study I we employed functional magnetic resonance imaging (fMRI) to detect the brain basis of volitional appetite control and its alterations in obesity. In Studies II-III we used diffusion tensor imaging (DTI) and voxel-based morphometry (VBM) to quantify the effects of obesity and the effects of weight loss on structural integrity of the brain. In study IV we used positron emission tomography (PET) with [18F]-FDG in fasting state and during euglycemic hyperinsulinemia to quantify effects of obesity and weight loss on brain glucose uptake. The fMRI experiment revealed that a fronto-parietal network is involved in volitional appetite control. Obese subjects had lower medial frontal and dorsal striatal brain activity during cognitive appetite control and increased functional connectivity within the appetite control circuit. Obese subjects had initially lower grey matter and white matter densities than healthy controls in VBM analysis and loss of integrity in white matter tracts as measured by DTI. They also had initially elevated glucose metabolism under insulin stimulation but not in fasting state. After the weight loss following bariatric surgery, obese individuals’ brain volumes recovered and the insulin-induced increase in glucose metabolism was attenuated. In conclusion, obesity is associated with altered brain function, coupled with loss of structural integrity and elevated glucose metabolism, which are likely signs of adverse health effects to the brain. These changes are reversed by weight loss after bariatric surgery, implicating that weight loss has a causal role on these adverse cerebral changes. Altogether these findings suggest that weight loss also promotes brain health.Key words: brain, obesity, bariatric surgery, appetite control, structural magnetic resonanceLihavuus yleistyy nopeasti koko maailmassa ja se on yksi suurimmista terveydenhuollon tulevaisuuden haasteista. Lihavuus lisää riskiä sairastua useisiin sairauksiin mm. verenpainetautiin, diabetekseen, tuki- ja liikuntaelinten sairauksiin ja useisiin syöpiin. Lihavilla on havaittu aivojen palkkiojärjestelmän reagoivan yliaktiivisesti ruokaan liittyviin ärsykkeisiin ja toisaalta ruokahalua hillitsevien alueiden toiminnan on havaittu olevan heikompaa kuin normaalipainoisilla. Lihavuus aiheuttaa myös haitallisia muutoksia aivosolujen rakenteessa ja aineenvaihdunnassa. Näiden muutosten palautumispotentiaalia ei voida arvioida poikkileikkaustutkimuksissa. Tässä työssä tutkimme sairaalloisen lihavia lihavuusleikkaukseen valittuja potilaita, joiden aivokuvantamistuloksia verrattiin normaalipainoisten vastaaviin kuvauksiin. Potilaat tutkittiin myös kuusi kuukautta lihavuusleikkauksen jälkeen painonlaskun aiheuttamien aivomuutosten tutkimiseksi. Ensimmäisessä tutkimuksessa ruokahalun säätelyjärjestelmän toiminnan ja lihavuuden aiheuttamien muutosten selvittämiseksi käytettiin toiminnallista magneettikuvantamista (fMRI). Rakenteellisia muutoksia arvioitiin II ja III osatyössä diffuusiotensorikuvantamisella (DTI) sekä vokseliperustaisen morfometrian avulla (VBM). Neljännessä osatyössä aivojen sokeriaineenvaihduntaa tutkittiin positroniemissiotomografian (PET) avulla käyttämällä [18F]-FDG-merkkiainetta paastotilassa ja insuliini-stimulaation aikana. VBM -ja PET-menetelmiä käytettiin myös lihavuusl eikkauksen vaikutusten arviointiin. fMRI-kokeessa havaittiin, että ruokahalun säätelyyn osallistuu laaja hermoverkko jonka keskeiset osat sijoittuvat otsa- ja päälaenlohkoihin. Lihavilla tutkittavilla havaittiin alentuneet vasteet häntätumakkeessa ja etupihtipoimun alueella. Lisäksi heillä havaittiin voimakkaammat toiminnalliset yhteydet ruokahalun säätelyverkostossa. Lihavuus aiheuttaa aivoissa laajaa aivokudoksen harventumaa ja hermoratojen eheyden alentumaa. PET-tutkimuksessa havaittiin lihavuuden lisäävän aivojen insuliiniherkkyyttä. Puoli vuotta lihavuusleikkauksen jälkeen rakenteelliset ja aineenvaihdunnan muutokset palautuivat osittain.Siirretty Doriast

Altérations de l'intégrité de la matière blanche avec l'obésité

L'obésité est de plus en plus décrite comme une maladie chronique, complexe et progressive caractérisée par une accumulation anormale ou excessive de graisses corporelles nuisibles à la santé. En plus d'entraîner des altérations métaboliques, physiques et psychologiques importantes, cette condition est associée à une fonction cognitive altérée et une augmentation du risque de maladies neurodégénératives. Afin d'améliorer la prise en charge de l'obésité et de développer des interventions individualisées, il s'avère essentiel de mieux comprendre les facteurs impliqués dans sa physiopathologie, dont l'implication du cerveau. Cet organe joue un rôle central dans la régulation de l'appétit, la prise alimentaire et la prise de poids. Des études d'imagerie par résonnance magnétique (IRM) ont montré des altérations au niveau de la matière grise et de la matière blanche cérébrales avec l'obésité. Ces altérations pourraient être induites par les nombreux désordres métaboliques associés à l'obésité. À l'inverse, ces altérations pourraient rendre un individu vulnérable à l'environnement actuel, ce qui favoriserait le gain de poids. Pour mieux comprendre les mécanismes impliqués dans les altérations cérébrales observées avec l'obésité, il est important de mieux caractériser les différences cérébrales et d'examiner leurs implications dans le développement et la progression de l'obésité. Le Chapitre 1 de ce mémoire présente les résultats d'une méta-analyse visant à examiner les altérations de l'intégrité de la matière blanche dans un contexte d'obésité. Nous avons montré que les individus avec obésité sont caractérisés par une réduction de l'intégrité de la matière blanche dans la partie antérieure droite du corps calleux, un faisceau qui relie les régions frontales impliquées dans les processus cognitifs. Des études futures sont nécessaires pour valider les mécanismes et vérifier si les altérations cérébrales associées à l'obésité sont permanentes ou si elles peuvent être renversées à la suite d'une intervention visant à améliorer la santé cardiométabolique.Obesity is a chronic, complex and progressive disease characterized by an abnormal or excessive body fat accumulation that induces health issues. In addition to the well-known metabolic, physical and psychological alterations related to this disease, this condition is associated with impaired cognitive function and is a risk factor for neurodegenerative diseases. In order to improve the management of obesity and to develop individualized interventions, it is essential to better understand the factors involved in its physiopathology, including the involvement of the brain. This organ plays a central role in the regulation of appetite, food intake and weight gain. Magnetic resonance imaging (MRI) studies have shown alterations in the brain's grey matter and white matter with obesity. These brain abnormalities could be a consequence of the cardiometabolic alterations associated with obesity. Conversely, these brain differences might constitute risk factors for overeating and weight gain when individuals are exposed to favorable environmental or endogenous conditions. To better understand the mechanisms underlying brain alterations observed with obesity, it remains important to better characterize the brain differences and examine their implications in the development and progression of obesity. The Chapter 1 presents the results of a meta-analysis aiming to examine the most robust and reliable white matter integrity alterations with obesity. Our findings provide evidence that obesity is consistently associated with reduced white matter integrity in the genu of the corpus callosum, a region linking frontal areas involved in cognitive function. Future studies are needed to identify the mechanisms linking obesity with loss of white matter integrity and to verify if these brain alterations are permanent or whether they can be reversed after interventions targeting cardiometabolic health

Computational approaches to predicting treatment response to obesity using neuroimaging

Obesity is a worldwide disease associated with multiple severe adverse consequences and comorbid conditions. While an increased body weight is the defining feature in obesity, etiologies, clinical phenotypes and treatment responses vary between patients. These variations can be observed within individual treatment options which comprise lifestyle interventions, pharmacological treatment, and bariatric surgery. Bariatric surgery can be regarded as the most effective treatment method. However, long-term weight regain is comparably frequent even for this treatment and its application is not without risk. A prognostic tool that would help predict the effectivity of the individual treatment methods in the long term would be essential in a personalized medicine approach. In line with this objective, an increasing number of studies have combined neuroimaging and computational modeling to predict treatment outcome in obesity. In our review, we begin by outlining the central nervous mechanisms measured with neuroimaging in these studies. The mechanisms are primarily related to reward-processing and include "incentive salience" and psychobehavioral control. We then present the diverse neuroimaging methods and computational prediction techniques applied. The studies included in this review provide consistent support for the importance of incentive salience and psychobehavioral control for treatment outcome in obesity. Nevertheless, further studies comprising larger sample sizes and rigorous validation processes are necessary to answer the question of whether or not the approach is sufficiently accurate for clinical real-world application