Changes in Hypothalamic Subunits Volume and Their Association with Metabolic Parameters and Gastrointestinal Appetite-Regulating Hormones Following Bariatric Surgery

Background : Some nuclei of the hypothalamus are known for their important roles in maintaining energy homeostasis and regulating food intake. Moreover, obesity has been associated with hypothalamic inflammation and morphological alterations, as indicated by increased volume. However, the reversibility of these changes after bariatric surgery-induced weight loss remains underexplored. Objective : The aim of this study was to characterize volume changes in hypothalamic subunits up to two years following bariatric surgery and to determine whether these differences were associated with changes in metabolic parameters and levels of gastrointestinal appetite-regulating hormone levels. Methods : Participants with severe obesity undergoing bariatric surgery were recruited. They completed high-resolution T1-weighted brain magnetic resonance imaging (MRI) before bariatric surgery and at 4, 12 and 24 months post-surgery. Blood samples collected during the fasting and postprandial states were analyzed for glucagon-like peptide 1 (GLP-1), peptide YY (PYY), and ghrelin concentrations. The hypothalamus was segmented into 5 subunits per hemisphere using a publicly available automated tool. Linear mixed-effects models were employed to examine volume changes between visits and their associations with variables of interest. Results : A total of 73 participants (mean age 44.5 ± 9.1 years, mean BMI 43.5 ± 4.1 kg/m 2) were included at baseline. Significant volume reductions were observed in the whole left hypothalamus 24 months post-surgery. More specifically, decreases were noted in both the left anterior-superior and left posterior subunits at 12 and 24 months post-surgery (all p<0.05, after FDR correction). These reductions were significantly associated with the percentage of total weight loss (both p<0.001), improvements in systolic blood pressure (both subunits p<0.05), and an increase in postprandial PYY (both subunits p<0.05). Conclusion : These results suggest that some hypothalamic morphological alterations observed in the context of obesity could potentially be reversed with bariatric surgery induced-weight loss. ### Competing Interest Statement A. T. and L.B. are recipients of research grant support from Johnson & Johnson Medical Companies and Medtronic for studies on bariatric surgery and the Research Chair in Bariatric and Metabolic Surgery at IUCPQ and Laval University, respectively. No author declared a conflict of interest relevant to the content of the manuscript. ### Funding Statement This study is supported 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 trial 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. A. L. is the recipient of a scholarship from the Canadian Institutes of Health Research and of a Master's Training Scholarships from Fonds de la recherche du Québec . A.M. and M.D. are the recipient of a Research Scholars - Junior 1 award from the Fonds de la recherche du Québec - Santé. A.C.C. holds the Canada Research Chair in Molecular Imaging of Diabetes. The co-investigators and collaborators of the REMISSION study are (alphabetical order): Bégin C, Biertho L, Bouvier M, Biron S, Cani P, Carpentier A, Dagher A, Dubé F, Fergusson A, Fulton S, Hould FS, Julien F, Kieffer T, Laferrère B, Lafortune A, Lebel S, Lescelleur O, Levy E, Marette A, Marceau S, Michaud A, Picard F, Poirier P, Richard D, Schertzer J, Tchernof A, Vohl MC. ### 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: Ethics committee/IRB of the Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec-Université Laval (IUCPQ-UL) gave ethical approval for this work. 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.