Department of Biobehavioral Health Sciences, School of Nursing, University of Pennsylvania, Philadelphia, PA 19104, USA.
Institute of Diabetes, Obesity and Metabolism and School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA 19104, USA.
Cell Rep. 2020 Apr 21;31(3):107543. doi: 10.1016/j.celrep.2020.107543.
The anorectic and weight-suppressive effects of growth differentiation factor-15 (GDF15) are attracting considerable attention for treating obesity. Current experiments in rats investigate whether GDF15 induces an aversive visceral malaise-based state that mediates its acute anorectic effect and, through aversion conditioning, exerts longer-term anorexia. Visceral malaise, conditioned affective food responses (taste reactivity), gastric emptying (GE), food intake, and body weight are evaluated after acute and chronic systemic dosing of GDF15 or long-acting Fc-GDF15. Pica, a marker of visceral malaise, is present at all anorectic GDF15 doses. Moreover, malaise induced by GDF15 does not decline over time, suggesting the lack of an improved tolerance after prolonged exposure. One association between GDF15 and novel food conditions a disgust/aversive response that persists beyond GDF15 acute action. Delayed GE is not a requirement for GDF15-induced anorexia. Clinical studies are required to evaluate whether GDF15's aversive-state-based anorexia will be contraindicated as an obesity treatment.
生长分化因子 15（GDF15）的厌食和体重抑制作用引起了人们对治疗肥胖的极大关注。目前的大鼠实验研究了 GDF15 是否会引起一种令人厌恶的内脏不适状态，这种状态介导其急性厌食作用，并通过厌恶条件作用，产生长期的厌食。急性和慢性全身给予 GDF15 或长效 Fc-GDF15 后，评估内脏不适、条件性食物反应（味觉反应）、胃排空（GE）、食物摄入和体重。在所有引起厌食的 GDF15 剂量下都存在一种标志内脏不适的异食癖。此外，GDF15 引起的不适不会随时间而下降，这表明在长时间暴露后，没有改善的耐受性。GDF15 与新食物之间的一种关联引起了一种持续存在于 GDF15 急性作用之外的厌恶/厌恶反应。GE 的延迟不是 GDF15 引起厌食的必要条件。需要进行临床研究来评估 GDF15 基于厌恶状态的厌食是否会被排除在肥胖治疗之外。
