Altered endocannabinoid-dynamics in craniopharyngioma patients and their association with HPA-axis disturbances

Abstract

Objective Patients with craniopharyngioma (CP) frequently suffer from morbid obesity. Endocannabinoids (ECs) are involved in weight gain and rewarding behavior but have not been investigated in this context. Design Cross-sectional single-center study. Methods Eighteen patients with CP and 16 age- and sex-matched controls were included. Differences in endocannabinoids (2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine (AEA)) and endocannabinoid-like molecules (oleoyl ethanolamide (OEA), palmitoyl ethanolamide (PEA), and arachidonic acid (AA) were measured at baseline and following endurance exercise. We further explored ECs-dynamics in relation to markers of HPA-axis activity (ACTH, cortisol, copeptin) and hypothalamic damage. Results Under resting conditions, independent of differences in BMI, 2-AG levels were more than twice as high in CP patients compared to controls. In contrast, 2-AG and OEA level increased in response to exercise in controls but not in CP patients, while AEA levels decreased in controls. As expected, exercise increased ACTH and copeptin levels in controls only. In a mixed model analysis across time and group, HPA measures did not provide additional information for explaining differences in 2-AG levels. However, AEA levels were negatively influenced by ACTH and copeptin levels, while OEA levels were negatively predicted by copeptin levels only. There were no significant differences in endocannabinoids depending on hypothalamic involvement. Conclusion Patients with CP show signs of a dysregulated endocannabinoid system under resting conditions as well as following exercise in comparison to healthy controls. Increased 2-AG levels under resting conditions and the missing response to physical activity could contribute to the metabolic phenotype of CP patients.

Use of Cannabis and Cannabinoids for Treatment of Cancer

“…In consistence with downregulation of AEA in glioma and hepatocellular carcinoma [ 78 , 100 ], the functional studies support a tumor suppressive role of AEA in head and neck and laryngeal squamous cell carcinomas [ 119 , 120 ]. Although 2-AG was elevated in various human malignancies [ 55 , 78 , 100 , 117 , 118 ], the functional evidence does not support an oncogenic role of 2-AG in tumor progression. Indeed, 2-AG exhibits an anticancer property in several model systems.…”

“…Additionally, the concentrations of 2-AG and AEA were higher in CRC cells than in healthy neighboring tissues [ 71 , 73 , 115 , 116 ]. The levels of plasma and/or tissue 2-AG are elevated in colorectal cancer [ 55 ], craniopharyngioma [ 117 ], diffuse large B-cell lymphoma [ 118 ], glioma [ 78 ], and hepatocellular carcinoma [ 100 ], whereas the levels of AEA are reduced in hepatocellular carcinoma [ 100 ] and glioma [ 78 ]. In consistence with downregulation of AEA in glioma and hepatocellular carcinoma [ 78 , 100 ], the functional studies support a tumor suppressive role of AEA in head and neck and laryngeal squamous cell carcinomas [ 119 , 120 ].…”

Gut Microbiota Composition and Metabolic Characteristics in Patients with Craniopharyngioma

“…The gut microbiota, comprising fungi, bacteria, bacteriophages, archaea, protozoa, and viruses, in uences hosts' neuronal function through neurotransmitters, neuroactive compounds or other substances [6][7][8][9]. Moreover, the gut microbiota can interact with the hosts' hypothalamic-pituitary-adrenal (HPA) axis by altering the individual's neuroendocrine system [10,11]. Like gliomas, pituitary neuroendocrine tumors (Pit-NETs), and other intracranial disorders, patients with CP may experience changes in the composition and metabolism of their gut microbiota, which could further impact the course of their disease.…”

Gut microbiota composition and metabolic characteristics in patients with Craniopharyngioma

“…The gut microbiota, comprising fungi , bacteria , bacteriophages , archaea , protozoa , and viruses , influences hosts’ neuronal function through neurotransmitters, neuroactive compounds or other substances [ 6 – 9 ]. Moreover, the gut microbiota can interact with the hosts’ hypothalamic-pituitary-adrenal (HPA) axis by altering the individual’s neuroendocrine system [ 10 , 11 ]. Like gliomas, pituitary neuroendocrine tumors (Pit-NETs), and other intracranial disorders, patients with CP may experience changes in the composition and metabolism of their gut microbiota, which could further impact the course of their disease.…”