Changes in hypothalamic subunits volume and their association with metabolic parameters and gastrointestinal...

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. The aim of this study was to characterize volume changes in hypothalamic subunits up to 2 years following bariatric surgery. A secondary objective was to explore whether changes in hypothalamic subunit volumes were associated with changes in metabolic parameters and levels of gastrointestinal appetite-regulating hormones. 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 concentrations of glucagon-like peptide 1 (GLP-1), peptide YY (PYY), and ghrelin. The hypothalamus was segmented into five 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. A total of 73 participants (mean age 44.5 ± 9.1 years; mean body mass index (BMI) 43.5 ± 4.1 kg/m²) were included at baseline, with 22 participants completing 24-month follow-up. 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 false discovery rate (FDR) correction). Smaller volumes in these subunits were significantly associated with a greater percentage of total weight loss (both subunits p < 0.001), as well as with higher postprandial PYY levels (both subunits p < 0.05). These findings suggest that some hypothalamic morphological alterations observed in the context of obesity could potentially be reversed following bariatric surgery-induced weight loss.