<b>Hypothalamic inflammation improves through bariatric surgery and hypothalamic volume predicts short-term weight loss response in adults with or without type 2 diabetes.</b>

Abstract

<p dir="ltr"><b>OBJECTIVE: </b>Preclinical research implicates hypothalamic inflammation (HI) in obesity and type 2 diabetes pathophysiology. However, their pathophysiological relevance and potential reversibility need to be better defined. We sought to evaluate the effect of bariatric surgery (BS) on radiologic biomarkers of HI and the association between the severity of such radiologic alterations and post-BS weight loss (WL)-trajectories. The utility of cerebrospinal fluid large extracellular vesicles (CSF-lEV) enriched for microglial and astrocyte markers in studying HI was also explored.</p><p dir="ltr"><b>RESEARCH DESIGN AND METHODS:</b><b> </b>We included 72 individuals with obesity (20 with/52 without type 2 diabetes) and 24 controls. Participants underwent lumbar puncture and 3T magnetic resonance imaging at baseline and 1-year post-BS. We assessed mean hypothalamic diffusivity (MD) (higher values indicate lesser microstructural integrity) and the volume of the whole and main hypothalamic subregions. CSF-lEV enriched for glial and astrocyte markers were determined by flow cytometry.</p><p dir="ltr"><b>RESULTS: </b>Compared with controls, obesity and type 2 diabetes groups showed a larger volume and higher MD in the hypothalamic tubular inferior region, the area encompassing the Arcuate nucleus. These radiological alterations were positively associated with baseline anthropometric and metabolic measures and improved post-BS. A larger baseline tubular inferior hypothalamic volume was independently related to lesser WL one and two years after BS. CSF-lEV did not differ between groups and were unrelated to WL-trajectories.</p><p dir="ltr"><b>CONCLUSIONS: </b>These findings suggest HI improvement after BS and may support a role for HI in modulating the weight loss response to these interventions.</p>