Sustained improvements in brain health and metabolic markers 24 months following bariatric surgery

Background Obesity and its metabolic complications are associated with lower gray matter (GM) and white matter (WM) density, whereas weight loss after bariatric surgery leads to an increase in both measures. These increases of GM and WM density are significantly associated with post-operative weight loss and improvement of the metabolic/inflammatory profiles. While our recent studies demonstrated widespread increases in WM density 4 and 12 months after bariatric surgery, it is not clear if theses changes persist over time. The underlying mechanisms also remain unknown. In this regard, numerous studies demonstrate that the enlargement or hypertrophy of mature adipocytes, particularly in the visceral fat compartment, is an important marker of adipose tissue dysfunction and obesity-related cardiometabolic abnormalities. Objective To assess whether the previously observed increases in WM and GM densities are maintained 24 months post-surgery, and to examine if pre-operative abdominal omental (OM) and subcutaneous (SC) adipocyte diameters are associated with WM and GM changes after bariatric surgery. Methods 32 participants undergoing bariatric surgery were recruited. WM and GM densities were assessed from T1-weighted MRIs acquired prior to and 4-, 12-, and 24-months post-surgery using voxel-based morphometry. OM and SC adipose tissue samples were collected during the surgical procedure. OM and SC adipocyte diameters were measured by microscopy of fixed adipose tissue samples. Linear mixed-effects models were performed controlling for age, sex, surgery type, initial BMI, and diabetic status. Results The average weight loss at 24 months was 33.5±7.2%. A widespread increase in WM density was observed 24 months post-surgery mainly in the cerebellum, brainstem, and corpus callosum (p<0.05, FDR) as well as some regions in GM density. Greater baseline OM adipocyte diameter was associated with greater changes in total WM density at 24 months (p=0.008). A positive trend was observed between SC adipocyte diameter and changes in total WM density at 24 months (p=0.05). Conclusion Our results show prolonged increases of WM and GM densities up to 24 months post-bariatric surgery. Greater preoperative OM adipocyte diameter is associated with greater increases in WM density at 24 months, suggesting that individuals with excess visceral adiposity might benefit the most from surgery. ### Competing Interest Statement A.T. and L.B. receive research funding from Johnson & Johnson, Medtronic and GI Windows for studies on bariatric surgery. A.T. and L.B. acted as consultants for Bausch Health and Novo Nordisk. A.T. is a consultant for Biotwin. The other authors had no conflict of interest to disclose. ### Funding Statement This study was funded by a Team grant from the Canadian Institutes of Health Research (CIHR) on bariatric care (TB2-138776) and an Investigator-initiated study grant from Johnson & Johnson Medical Companies (Grant ETH-14-610). Funding sources for the study had no role in the design, conduct or management of the study, in data collection, analysis or interpretation of data, or in the preparation of the present manuscript and decision to publish. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Research Ethics Committee (CER) of the Centre de recherche de Institut universitaire de cardiologie et pneumologie de Quebec - Universite Laval (IUCPQ-UL) gave ethical approval for this work (2016-2569, 21237). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.