Impaired postprandial GLP-2 response enhances endotoxemia, systemic inflammation, and kidney injury in metabolic dysfunction-associated steatohepatitis (MASH): effect of phospholipid curcumin meriva
We investigate the role of homeostatic mechanisms involved in acute, postprandial nutrient metabolism and nutrient-induced systemic inflammation in CKD presence and progression in Metabolic dysfunction-associated steatohepatitis (MASH). We assessed postprandial incretins (GLP-1 and GIP), intestinotr...
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Taylor & Francis Group
2024-12-01
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| Series: | Gut Microbes |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/19490976.2024.2424907 |
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| author | Giovanni Musso Mella Alberto Filippo Mariano Maurizio Cassader Franco De Michieli Antonella Riva Giovanna Petrangolini Stefano Togni Silvia Pinach Roberto Gambino |
| author_facet | Giovanni Musso Mella Alberto Filippo Mariano Maurizio Cassader Franco De Michieli Antonella Riva Giovanna Petrangolini Stefano Togni Silvia Pinach Roberto Gambino |
| author_sort | Giovanni Musso |
| collection | DOAJ |
| description | We investigate the role of homeostatic mechanisms involved in acute, postprandial nutrient metabolism and nutrient-induced systemic inflammation in CKD presence and progression in Metabolic dysfunction-associated steatohepatitis (MASH). We assessed postprandial incretins (GLP-1 and GIP), intestinotropic hormone GLP-2, endotoxin LPS, Zonulin (a marker of intestinal permeability), hepatokines, adipokines and NF-kB activation in circulating MNCs during a meal tolerance test in 52 biopsy proven MASH patients randomized to curcumin Meriva or placebo and 26 matched controls. At baseline, MASH-CKD had a lower GLP-2 response and a 2-fold higher postprandial LPS and NF-kB activation in MNCs than MASH patients without CKD, but similar remaining postprandial or fasting parameters. Postprandial IAUC GLP-2 predicted the presence of CKD in MASH (OR = 0.43, 95%CI:0.32-0.80, p = 0.008) independently of liver histology and traditional risk factors. After 72 weeks, changes in IAUC GLP-2 independently predicted the presence of CKD (OR = 0.49, 95%CI:0.21-0.73, p = 0.010) and eGFR changes [β(SE) = 0.510(0.007, p = 0.006] at end-of-treatment, In MASH, an impaired GLP-2 response to meals is associated with intestinal barrier dysfunction, endotoxemia and NF-kB-mediated systemic inflammation and may promote renal dysfunction and CKD. These data provide the rationale for evaluating GLP-2 analogues in MASH-related CKD. |
| format | Article |
| id | doaj-art-27aee9611363417ea5dc3b9b2ee08c80 |
| institution | OA Journals |
| issn | 1949-0976 1949-0984 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Gut Microbes |
| spelling | doaj-art-27aee9611363417ea5dc3b9b2ee08c802025-08-20T02:18:05ZengTaylor & Francis GroupGut Microbes1949-09761949-09842024-12-0116110.1080/19490976.2024.2424907Impaired postprandial GLP-2 response enhances endotoxemia, systemic inflammation, and kidney injury in metabolic dysfunction-associated steatohepatitis (MASH): effect of phospholipid curcumin merivaGiovanni Musso0Mella Alberto1Filippo Mariano2Maurizio Cassader3Franco De Michieli4Antonella Riva5Giovanna Petrangolini6Stefano Togni7Silvia Pinach8Roberto Gambino9MECAU Department San Luigi Gonzaga Hospital, Turin, ItalyDepartment of Nephrology, Città della Salute e della Scienza Hospital, University of Turin, Turin, ItalyDepartment of Nephrology, Città della Salute e della Scienza Hospital, University of Turin, Turin, ItalyDepartment of Medical Sciences, Città della Salute e della Scienza Hospital, University of Turin, Turin, ItalyDepartment of Medical Sciences, Città della Salute e della Scienza Hospital, University of Turin, Turin, ItalyR & D Indena S.p.A, Milan, ItalyR & D Indena S.p.A, Milan, ItalyR & D Indena S.p.A, Milan, ItalyDepartment of Medical Sciences, Città della Salute e della Scienza Hospital, University of Turin, Turin, ItalyDepartment of Medical Sciences, Città della Salute e della Scienza Hospital, University of Turin, Turin, ItalyWe investigate the role of homeostatic mechanisms involved in acute, postprandial nutrient metabolism and nutrient-induced systemic inflammation in CKD presence and progression in Metabolic dysfunction-associated steatohepatitis (MASH). We assessed postprandial incretins (GLP-1 and GIP), intestinotropic hormone GLP-2, endotoxin LPS, Zonulin (a marker of intestinal permeability), hepatokines, adipokines and NF-kB activation in circulating MNCs during a meal tolerance test in 52 biopsy proven MASH patients randomized to curcumin Meriva or placebo and 26 matched controls. At baseline, MASH-CKD had a lower GLP-2 response and a 2-fold higher postprandial LPS and NF-kB activation in MNCs than MASH patients without CKD, but similar remaining postprandial or fasting parameters. Postprandial IAUC GLP-2 predicted the presence of CKD in MASH (OR = 0.43, 95%CI:0.32-0.80, p = 0.008) independently of liver histology and traditional risk factors. After 72 weeks, changes in IAUC GLP-2 independently predicted the presence of CKD (OR = 0.49, 95%CI:0.21-0.73, p = 0.010) and eGFR changes [β(SE) = 0.510(0.007, p = 0.006] at end-of-treatment, In MASH, an impaired GLP-2 response to meals is associated with intestinal barrier dysfunction, endotoxemia and NF-kB-mediated systemic inflammation and may promote renal dysfunction and CKD. These data provide the rationale for evaluating GLP-2 analogues in MASH-related CKD.https://www.tandfonline.com/doi/10.1080/19490976.2024.2424907SteatohepatitisNF-kBpostprandialeGFRalbuminuriachemokine |
| spellingShingle | Giovanni Musso Mella Alberto Filippo Mariano Maurizio Cassader Franco De Michieli Antonella Riva Giovanna Petrangolini Stefano Togni Silvia Pinach Roberto Gambino Impaired postprandial GLP-2 response enhances endotoxemia, systemic inflammation, and kidney injury in metabolic dysfunction-associated steatohepatitis (MASH): effect of phospholipid curcumin meriva Gut Microbes Steatohepatitis NF-kB postprandial eGFR albuminuria chemokine |
| title | Impaired postprandial GLP-2 response enhances endotoxemia, systemic inflammation, and kidney injury in metabolic dysfunction-associated steatohepatitis (MASH): effect of phospholipid curcumin meriva |
| title_full | Impaired postprandial GLP-2 response enhances endotoxemia, systemic inflammation, and kidney injury in metabolic dysfunction-associated steatohepatitis (MASH): effect of phospholipid curcumin meriva |
| title_fullStr | Impaired postprandial GLP-2 response enhances endotoxemia, systemic inflammation, and kidney injury in metabolic dysfunction-associated steatohepatitis (MASH): effect of phospholipid curcumin meriva |
| title_full_unstemmed | Impaired postprandial GLP-2 response enhances endotoxemia, systemic inflammation, and kidney injury in metabolic dysfunction-associated steatohepatitis (MASH): effect of phospholipid curcumin meriva |
| title_short | Impaired postprandial GLP-2 response enhances endotoxemia, systemic inflammation, and kidney injury in metabolic dysfunction-associated steatohepatitis (MASH): effect of phospholipid curcumin meriva |
| title_sort | impaired postprandial glp 2 response enhances endotoxemia systemic inflammation and kidney injury in metabolic dysfunction associated steatohepatitis mash effect of phospholipid curcumin meriva |
| topic | Steatohepatitis NF-kB postprandial eGFR albuminuria chemokine |
| url | https://www.tandfonline.com/doi/10.1080/19490976.2024.2424907 |
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