OBJECTIVE 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 radiological biomarkers of HI and the association between the severity of such radiological alterations and post-BS weight loss (WL) trajectories. The utility of cerebrospinal fluid large extracellular vesicles (CSF-lEVs) enriched for microglial and astrocyte markers in studying HI was also explored. RESEARCH DESIGN AND METHODS We included 72 individuals with obesity (20 with and 52 without type 2 diabetes) and 24 control individuals. Participants underwent lumbar puncture and 3-T MRI at baseline and 1-year post-BS. We assessed hypothalamic mean diffusivity (MD) (higher values indicate lesser microstructural integrity) and the volume of the whole and main hypothalamic subregions. CSF-lEVs enriched for glial and astrocyte markers were determined by flow cytometry. RESULTS Compared with control group, the 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 1 and 2 years after BS. CSF-lEVs did not differ among groups and were unrelated to WL trajectories. CONCLUSIONS These findings suggest HI improvement after BS and may support a role for HI in modulating the WL response to these interventions.

中文翻译：

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下丘脑炎症通过减肥手术得到改善，下丘脑体积可预测患有或不患有 2 型糖尿病的成人的短期减肥反应

目的 临床前研究表明下丘脑炎症 (HI) 与肥胖和 2 型糖尿病病理生理学有关。然而，它们的病理生理学相关性和潜在的可逆性需要更好地定义。我们试图评估减肥手术 (BS) 对 HI 放射学生物标志物的影响，以及此类放射学改变的严重程度与 BS 后体重减轻 (WL) 轨迹之间的关联。还探讨了富含小胶质细胞和星形胶质细胞标记物的脑脊液大细胞外囊泡（CSF-1EV）在研究 HI 中的效用。研究设计和方法 我们纳入了 72 名肥胖患者（20 名患有 2 型糖尿病，52 名没有 2 型糖尿病）和 24 名对照个体。参与者在基线和 BS 后 1 年接受了腰椎穿刺和 3-T MRI。我们评估了下丘脑平均扩散率（MD）（较高的值表明微观结构完整性较差）以及整个和主要下丘脑分区的体积。通过流式细胞术测定富含神经胶质和星形胶质细胞标记物的CSF-1EV。结果与对照组相比，肥胖组和2型糖尿病组的下丘脑管状下区（弓状核区域）体积更大，MD更高。这些放射学改变与基线人体测量和代谢测量值呈正相关，并改善了 BS 后的情况。 BS 后 1 年和 2 年较大的基线管状下丘脑体积与较小的 WL 独立相关。 CSF-1EV 在各组之间没有差异，并且与 WL 轨迹无关。结论 这些发现表明 BS 后 HI 有所改善，并可能支持 HI 在调节 WL 对这些干预措施的反应中的作用。