Garella Rachele, Palmieri Francesco, Tarchi Livio, Tani Alessia, Chellini Flaminia, Guarnieri Giulia, Morelli Annamaria, Bernacchioni Caterina, Rovero Paolo, Ricca Valdo, Castellini Giovanni, Sassoli Chiara, Squecco Roberta
Department of Experimental and Clinical Medicine, Section of Physiological Sciences, University of Florence, Florence, Italy.
Department of Health Sciences, Psychiatry Unit, University of Florence, Florence, Italy.
J Cell Mol Med. 2025 Jun;29(11):e70629. doi: 10.1111/jcmm.70629.
Growth Differentiation Factor 15 (GDF15) is a peptide from the transforming growth factor (TGF)-β superfamily, typically found at low levels in mammalian tissues, but significantly upregulated during cellular stress or injury. Initially recognised for its role in inducing anorexia and vomiting, GDF15 is now seen as a broader regulator of homeostasis, although its effects on gastrointestinal function remain unclear. This study examined GDF15's impact on the gastric fundus, a key region for appetite regulation. In ex vivo rodent gastric smooth muscle, GDF15 receptors were detected, and exposure to GDF15 caused smooth muscle depolarization, leading to increased mechanical activation. Morphological analyses revealed changes in the contractile apparatus, resembling cholinergic excitatory pathways. These effects were blocked by atropine, indicating muscarinic receptor involvement. Taken together, these findings suggest that GDF15 enhances gastric contractility by influencing cholinergic tone. Further studies will shed light on its mechanism of action and on the potential translational perspective of current results, elucidating whether elevated plasma levels of GDF15 observed in several physiological and pathological conditions can also have repercussions in gastric physiology, appetite regulation and weight loss.
生长分化因子15（GDF15）是转化生长因子（TGF）-β超家族的一种肽，通常在哺乳动物组织中含量较低，但在细胞应激或损伤时会显著上调。GDF15最初因其在诱导厌食和呕吐中的作用而被认识，现在被视为体内平衡的更广泛调节因子，尽管其对胃肠功能的影响仍不清楚。本研究考察了GDF15对胃底的影响，胃底是食欲调节的关键区域。在离体啮齿动物胃平滑肌中检测到GDF15受体，暴露于GDF15会导致平滑肌去极化，从而导致机械激活增加。形态学分析显示收缩装置发生变化，类似于胆碱能兴奋途径。这些效应被阿托品阻断，表明毒蕈碱受体参与其中。综上所述，这些发现表明GDF15通过影响胆碱能张力来增强胃收缩力。进一步的研究将阐明其作用机制以及当前结果的潜在转化前景，阐明在几种生理和病理条件下观察到的血浆GDF15水平升高是否也会对胃生理学、食欲调节和体重减轻产生影响。
