Ziegler Andreas Kraag, Christensen Mette, Jørgensen Henrik Løvendahl, Fenger Mogens, Myrup Sara Fogh, Dirksen Carsten, Madsbad Sten
Department of Clinical Biochemistry, Hvidovre University Hospital, University of Copenhagen, RegionH, Hvidovre, Denmark.
The Centre for Physical Activity Research, Rigshospitalet University Hospital, University of Copenhagen, RegionH, Copenhagen, Denmark.
Sci Rep. 2025 Aug 7;15(1):28916. doi: 10.1038/s41598-025-14537-4.
Human obesity is a state of hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis and dysfunction of the sympathetic nervous system (SNS). It is unclear whether weight loss will normalize this apparent dysfunction and if potential changes are of short -or long-term duration. In this study, we test how weight reduction following Roux-en-Y Gastric Bypass (RYGB) surgery affects the HPA-axis and SNS activity for a follow-up period of 2 years. We show that a ≈ 30% reduction in bodyweight following RYGB, is accompanied by an increase in circulating cortisol, and decrease in the concentrations of systemic metanephrines concomitant with a transient reduction in systolic blood pressure, and that the endocrine changes persist for at least 24 months post-surgery. The decrease in SNS activity was weakly, but significantly correlated with postoperative improvements in HbA1c. These findings suggests that the anatomical rearrangement of the gastrointestinal system by bariatric surgery, and the resulting marked decrease in body weight, have long-term impact on the autonomic nervous system. The biological significance of these findings is uncertain though it could be speculated that chronically elevated serum cortisol, may be involved in the development of osteoporosis, a well-known risk of bariatric surgery, as well as control of glucose and lipid metabolism. Furthermore, the chronic reduction in metanephrines observed, suggest that SNS depression may contribute to both a reduction in blood pressure and better glycemic control following surgery. We collectively demonstrate that RYGB surgery has an early and persisting impact on the HPA-axis and the sympathetic nervous system, and that this is associated with bodyweight reduction and improved glycemic control.
人类肥胖是下丘脑 - 垂体 - 肾上腺（HPA）轴功能亢进和交感神经系统（SNS）功能障碍的一种状态。目前尚不清楚体重减轻是否会使这种明显的功能障碍恢复正常，以及潜在的变化是短期还是长期的。在本研究中，我们测试了Roux - en - Y胃旁路术（RYGB）后体重减轻如何在2年的随访期内影响HPA轴和SNS活性。我们发现，RYGB术后体重减轻约30%，伴随着循环皮质醇增加、全身间甲肾上腺素浓度降低，同时收缩压短暂下降，并且这些内分泌变化在术后至少持续24个月。SNS活性的降低与糖化血红蛋白（HbA1c）术后改善呈弱但显著的相关性。这些发现表明，减肥手术对胃肠道系统的解剖结构重排以及由此导致的体重显著下降，对自主神经系统有长期影响。尽管可以推测，长期升高的血清皮质醇可能参与了骨质疏松症的发生（这是减肥手术众所周知的风险）以及血糖和脂质代谢的控制，但这些发现的生物学意义尚不确定。此外，观察到的间甲肾上腺素的慢性降低表明，SNS抑制可能有助于术后血压降低和血糖控制改善。我们共同证明，RYGB手术对HPA轴和交感神经系统有早期且持续的影响，并且这与体重减轻和血糖控制改善有关。
