Project description:Anorexia can occur as a serious complication of chronic disease. Increasing evidence suggests that inflammation plays a major role, along with a hypothalamic dysregulation characterized by locally elevated serotonin levels. The present study was undertaken to further explore the connections between peripheral inflammation, anorexia and hypothalamic serotonin metabolism and signaling pathways. We studied transcriptomic changes and serotonergic activity in the hypothalamus of mice after an intraperitoneal injection with TNFα, IL-6 or a combination of TNFα and IL-6. C57BL/6 mice were intraperitoneally injected with TNFalpha, IL-6 Low, IL-6 High, combination TNF+IL-6 Low or combination TNF+IL-6 High. Each group comprised of 12 animals, of which 6 animals were used for transcriptomics.
Project description:Anorexia can occur as a serious complication of chronic disease. Increasing evidence suggests that inflammation plays a major role, along with a hypothalamic dysregulation characterized by locally elevated serotonin levels. The present study was undertaken to further explore the connections between peripheral inflammation, anorexia and hypothalamic serotonin metabolism and signaling pathways. We studied transcriptomic changes and serotonergic activity in the hypothalamus of mice after an intraperitoneal injection with TNFα, IL-6 or a combination of TNFα and IL-6.
Project description:Anorexia is a common symptom among cancer patients and contributes to malnutrition and insufficient food intake. In cancer-induced anorexia, food intake regulation in the hypothalamus appears to be impaired. A negative energy balance persists and accelerates muscle wasting and malnutrition. Moreover, it strongly affects mortality and survival in these patients. Here, we show that the neuropeptide Y system (NPY) appears to fail to respond adequately to changes in energy balance during cancer cachexia. In addition, we investigate the connection between serotonin and NPY release in hypothalamic cell lines. Hypothalamic neuronal cells mHypoE-46 (serotonin sensitive cells) and mHypoA-2/12 (serotonin unresponsive cells) were used to study the effect of serotonin on messenger NPY expression and NPY excretion.
Project description:Acetaminophen is a widely used antipyretic and analgesic drug, and its overdose is the leading cause of drug-induced acute liver failure. This study aimed to investigate the effect and mechanism of Lacticaseibacillus casei Shirota (LcS), an extensively used and highly studied probiotic, on acetaminophen-induced acute liver injury. C57BL/6 mice were gavaged with LcS suspension or saline once daily for 7 days before the acute liver injury was induced via intraperitoneal injection of 300 mg/kg acetaminophen. The results showed that LcS significantly decreased acetaminophen-induced liver and ileum injury, as demonstrated by reductions in the increases in aspartate aminotransferase, total bile acids, total bilirubin, indirect bilirubin and hepatic cell necrosis. Moreover, LcS alleviated the acetaminophen-induced intestinal mucosal permeability, elevation in serum IL-1α and lipopolysaccharide, and decreased levels of serum eosinophil chemokine (eotaxin) and hepatic glutathione levels. Furthermore, analysis of the gut microbiota and metabolome showed that LcS reduced the acetaminophen-enriched levels of Cyanobacteria, Oxyphotobacteria, long-chain fatty acids, cholesterol and sugars in the gut. Additionally, the transcriptome and proteomics showed that LcS mitigated the downregulation of metabolism and immune pathways as well as glutathione formation during acetaminophen-induced acute liver injury. This is the first study showing that pretreatment with LcS alleviates acetaminophen-enriched acute liver injury, and it provides a reference for the application of LcS.
