A 5:2 intermittent fasting regimen ameliorates NASH and fibrosis and blunts HCC development via hepatic PPARα and PCK1
The role and molecular mechanisms of intermittent fasting (IF) in non-alcoholic steatohepatitis (NASH) and its transition to hepatocellular carcinoma (HCC) are unknown. Here, we identified that an IF 5:2 regimen prevents NASH development as well as ameliorates established NASH and fibrosis without a...
Gespeichert in:
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
4 June 2024
|
| In: |
Cell metabolism
Year: 2024, Jahrgang: 36, Heft: 6, Pages: 1371-1393.e7 |
| ISSN: | 1932-7420 |
| DOI: | 10.1016/j.cmet.2024.04.015 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.cmet.2024.04.015 Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S1550413124001359 
|
| Verfasserangaben: | Suchira Gallage, Adnan Ali, Jose Efren Barragan Avila, Nogayhan Seymen, Pierluigi Ramadori, Vera Joerke, Laimdota Zizmare, David Aicher, Indresh K. Gopalsamy, Winnie Fong, Jan Kosla, Enrico Focaccia, Xin Li, Suhail Yousuf, Tjeerd Sijmonsma, Mohammad Rahbari, Katharina S. Kommoss, Adrian Billeter, Sandra Prokosch, Ulrike Rothermel, Florian Mueller, Jenny Hetzer, Danijela Heide, Benjamin Schinkel, Tim Machauer, Bernd Pichler, Nisar P. Malek, Thomas Longerich, Susanne Roth, Adam J. Rose, Johannes Schwenck, Christoph Trautwein, Mohammad M. Karimi, and Mathias Heikenwalder |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1909633208 | ||
| 003 | DE-627 | ||
| 005 | 20241220171151.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 241127s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.cmet.2024.04.015 |2 doi | |
| 035 | |a (DE-627)1909633208 | ||
| 035 | |a (DE-599)KXP1909633208 | ||
| 035 | |a (OCoLC)1475648281 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Gallage, Suchira |e VerfasserIn |0 (DE-588)1320655408 |0 (DE-627)188120037X |4 aut | |
| 245 | 1 | 2 | |a A 5:2 intermittent fasting regimen ameliorates NASH and fibrosis and blunts HCC development via hepatic PPARα and PCK1 |c Suchira Gallage, Adnan Ali, Jose Efren Barragan Avila, Nogayhan Seymen, Pierluigi Ramadori, Vera Joerke, Laimdota Zizmare, David Aicher, Indresh K. Gopalsamy, Winnie Fong, Jan Kosla, Enrico Focaccia, Xin Li, Suhail Yousuf, Tjeerd Sijmonsma, Mohammad Rahbari, Katharina S. Kommoss, Adrian Billeter, Sandra Prokosch, Ulrike Rothermel, Florian Mueller, Jenny Hetzer, Danijela Heide, Benjamin Schinkel, Tim Machauer, Bernd Pichler, Nisar P. Malek, Thomas Longerich, Susanne Roth, Adam J. Rose, Johannes Schwenck, Christoph Trautwein, Mohammad M. Karimi, and Mathias Heikenwalder |
| 246 | 3 | 0 | |a two |
| 246 | 3 | 3 | |a A five to two intermittent fasting regimen ameliorates NASH and fibrosis and blunts HCC development via hepatic PPARalpha and PCK1 |
| 264 | 1 | |c 4 June 2024 | |
| 300 | |a 31 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Online verfügbar: 7. Mai 2024, Artikelversion: 4. Juni 2024 | ||
| 500 | |a Gesehen am 27.11.2024 | ||
| 520 | |a The role and molecular mechanisms of intermittent fasting (IF) in non-alcoholic steatohepatitis (NASH) and its transition to hepatocellular carcinoma (HCC) are unknown. Here, we identified that an IF 5:2 regimen prevents NASH development as well as ameliorates established NASH and fibrosis without affecting total calorie intake. Furthermore, the IF 5:2 regimen blunted NASH-HCC transition when applied therapeutically. The timing, length, and number of fasting cycles as well as the type of NASH diet were critical parameters determining the benefits of fasting. Combined proteome, transcriptome, and metabolome analyses identified that peroxisome-proliferator-activated receptor alpha (PPARα) and glucocorticoid-signaling-induced PCK1 act co-operatively as hepatic executors of the fasting response. In line with this, PPARα targets and PCK1 were reduced in human NASH. Notably, only fasting initiated during the active phase of mice robustly induced glucocorticoid signaling and free-fatty-acid-induced PPARα signaling. However, hepatocyte-specific glucocorticoid receptor deletion only partially abrogated the hepatic fasting response. In contrast, the combined knockdown of Ppara and Pck1 in vivo abolished the beneficial outcomes of fasting against inflammation and fibrosis. Moreover, overexpression of Pck1 alone or together with Ppara in vivo lowered hepatic triglycerides and steatosis. Our data support the notion that the IF 5:2 regimen is a promising intervention against NASH and subsequent liver cancer. | ||
| 650 | 4 | |a fasting | |
| 650 | 4 | |a HCC | |
| 650 | 4 | |a IF | |
| 650 | 4 | |a intermittent fasting | |
| 650 | 4 | |a liver cancer | |
| 650 | 4 | |a MASH | |
| 650 | 4 | |a MASLD | |
| 650 | 4 | |a NAFLD | |
| 650 | 4 | |a NASH | |
| 700 | 1 | |a Ali, Sheikh Adnan |d 1991- |e VerfasserIn |0 (DE-588)1237251540 |0 (DE-627)1763611426 |4 aut | |
| 700 | 1 | |a Barragan Avila, José Efren |d 1992- |e VerfasserIn |0 (DE-588)133109996X |0 (DE-627)1890259675 |4 aut | |
| 700 | 1 | |a Seymen, Nogayhan |e VerfasserIn |4 aut | |
| 700 | 1 | |a Ramadori, Pierluigi |d 1977- |e VerfasserIn |0 (DE-588)142805947 |0 (DE-627)640131964 |0 (DE-576)33367880X |4 aut | |
| 700 | 1 | |a Joerke, Vera |e VerfasserIn |4 aut | |
| 700 | 1 | |a Zizmare, Laimdota |e VerfasserIn |0 (DE-588)1317218612 |0 (DE-627)1878963465 |4 aut | |
| 700 | 1 | |a Aicher, David |e VerfasserIn |0 (DE-588)1198751401 |0 (DE-627)1680929410 |4 aut | |
| 700 | 1 | |a Gopalsamy, Indresh K. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Fong, Winnie |e VerfasserIn |4 aut | |
| 700 | 1 | |a Kosla, Jan |e VerfasserIn |4 aut | |
| 700 | 1 | |a Focaccia, Enrico |d 1990- |e VerfasserIn |0 (DE-588)1323335757 |0 (DE-627)1883340470 |4 aut | |
| 700 | 1 | |a Li, Xin |e VerfasserIn |4 aut | |
| 700 | 1 | |a Yousuf, Suhail |e VerfasserIn |0 (DE-588)1321852355 |0 (DE-627)1881721566 |4 aut | |
| 700 | 1 | |a Sijmonsma, Tjeerd |e VerfasserIn |4 aut | |
| 700 | 1 | |a Rahbari, Mohammad |e VerfasserIn |0 (DE-588)1192953541 |0 (DE-627)1671484282 |4 aut | |
| 700 | 1 | |a Kommoss, Katharina |e VerfasserIn |0 (DE-588)1216661227 |0 (DE-627)1727913124 |4 aut | |
| 700 | 1 | |a Billeter, Adrian |d 1984- |e VerfasserIn |0 (DE-588)1071497499 |0 (DE-627)825950732 |0 (DE-576)433113804 |4 aut | |
| 700 | 1 | |a Prokosch, Sandra |e VerfasserIn |4 aut | |
| 700 | 1 | |a Rothermel, Ulrike |e VerfasserIn |4 aut | |
| 700 | 1 | |a Mueller, Florian |e VerfasserIn |4 aut | |
| 700 | 1 | |a Hetzer, Jenny |e VerfasserIn |0 (DE-588)1321867085 |0 (DE-627)1881733939 |4 aut | |
| 700 | 1 | |a Heide, Danijela |e VerfasserIn |0 (DE-588)1160541647 |0 (DE-627)1023813084 |0 (DE-576)505986116 |4 aut | |
| 700 | 1 | |a Schinkel, Benjamin |e VerfasserIn |4 aut | |
| 700 | 1 | |a Machauer, Tim |e VerfasserIn |4 aut | |
| 700 | 1 | |a Pichler, Bernd |d 1969- |e VerfasserIn |0 (DE-588)11579638X |0 (DE-627)077478738 |0 (DE-576)29008301X |4 aut | |
| 700 | 1 | |a Malek, Nisar Peter |d 1968- |e VerfasserIn |0 (DE-588)133116603 |0 (DE-627)534553710 |0 (DE-576)299634531 |4 aut | |
| 700 | 1 | |a Longerich, Thomas |d 1974- |e VerfasserIn |0 (DE-588)128494514 |0 (DE-627)373916124 |0 (DE-576)297178059 |4 aut | |
| 700 | 1 | |a Roth, Susanne |d 1981- |e VerfasserIn |0 (DE-588)14180663X |0 (DE-627)631813896 |0 (DE-576)32601764X |4 aut | |
| 700 | 1 | |a Rose, Adam J. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Schwenck, Johannes |e VerfasserIn |4 aut | |
| 700 | 1 | |a Trautwein, Christoph |e VerfasserIn |4 aut | |
| 700 | 1 | |a Karimi, Mohammad M. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Heikenwälder, Mathias |d 1976- |e VerfasserIn |0 (DE-588)1024541045 |0 (DE-627)720089840 |0 (DE-576)368599299 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Cell metabolism |d Amsterdam [u.a.] : Elsevier, 2005 |g 36(2024), 6 vom: Juni, Seite 1371-1393.e7 |h Online-Ressource |w (DE-627)477987451 |w (DE-600)2174469-5 |w (DE-576)252254643 |x 1932-7420 |7 nnas |a A 5:2 intermittent fasting regimen ameliorates NASH and fibrosis and blunts HCC development via hepatic PPARα and PCK1 |
| 773 | 1 | 8 | |g volume:36 |g year:2024 |g number:6 |g month:06 |g pages:1371-1393.e7 |g extent:31 |a A 5:2 intermittent fasting regimen ameliorates NASH and fibrosis and blunts HCC development via hepatic PPARα and PCK1 |
| 856 | 4 | 0 | |u https://doi.org/10.1016/j.cmet.2024.04.015 |x Verlag |x Resolving-System |z kostenfrei |3 Volltext |
| 856 | 4 | 0 | |u https://www.sciencedirect.com/science/article/pii/S1550413124001359 |x Verlag |z kostenfrei |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20241127 | ||
| 993 | |a Article | ||
| 994 | |a 2024 | ||
| 998 | |g 1024541045 |a Heikenwälder, Mathias |m 1024541045:Heikenwälder, Mathias |d 910000 |d 911700 |e 910000PH1024541045 |e 911700PH1024541045 |k 0/910000/ |k 1/910000/911700/ |p 34 |y j | ||
| 998 | |g 14180663X |a Roth, Susanne |m 14180663X:Roth, Susanne |d 910000 |d 910200 |d 50000 |e 910000PR14180663X |e 910200PR14180663X |e 50000PR14180663X |k 0/910000/ |k 1/910000/910200/ |k 0/50000/ |p 29 | ||
| 998 | |g 128494514 |a Longerich, Thomas |m 128494514:Longerich, Thomas |d 910000 |d 912000 |e 910000PL128494514 |e 912000PL128494514 |k 0/910000/ |k 1/910000/912000/ |p 28 | ||
| 998 | |g 1071497499 |a Billeter, Adrian |m 1071497499:Billeter, Adrian |d 50000 |e 50000PB1071497499 |k 0/50000/ |p 18 | ||
| 998 | |g 1216661227 |a Kommoss, Katharina |m 1216661227:Kommoss, Katharina |d 910000 |d 911300 |e 910000PK1216661227 |e 911300PK1216661227 |k 0/910000/ |k 1/910000/911300/ |p 17 | ||
| 998 | |g 1192953541 |a Rahbari, Mohammad |m 1192953541:Rahbari, Mohammad |d 60000 |d 61800 |e 60000PR1192953541 |e 61800PR1192953541 |k 0/60000/ |k 1/60000/61800/ |p 16 | ||
| 998 | |g 1321852355 |a Yousuf, Suhail |m 1321852355:Yousuf, Suhail |d 910000 |d 910200 |e 910000PY1321852355 |e 910200PY1321852355 |k 0/910000/ |k 1/910000/910200/ |p 14 | ||
| 998 | |g 1320655408 |a Gallage, Suchira |m 1320655408:Gallage, Suchira |p 1 |x j | ||
| 999 | |a KXP-PPN1909633208 |e 4623154742 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"origin":[{"dateIssuedKey":"2024","dateIssuedDisp":"4 June 2024"}],"recId":"1909633208","note":["Online verfügbar: 7. Mai 2024, Artikelversion: 4. Juni 2024","Gesehen am 27.11.2024"],"language":["eng"],"name":{"displayForm":["Suchira Gallage, Adnan Ali, Jose Efren Barragan Avila, Nogayhan Seymen, Pierluigi Ramadori, Vera Joerke, Laimdota Zizmare, David Aicher, Indresh K. Gopalsamy, Winnie Fong, Jan Kosla, Enrico Focaccia, Xin Li, Suhail Yousuf, Tjeerd Sijmonsma, Mohammad Rahbari, Katharina S. Kommoss, Adrian Billeter, Sandra Prokosch, Ulrike Rothermel, Florian Mueller, Jenny Hetzer, Danijela Heide, Benjamin Schinkel, Tim Machauer, Bernd Pichler, Nisar P. Malek, Thomas Longerich, Susanne Roth, Adam J. Rose, Johannes Schwenck, Christoph Trautwein, Mohammad M. Karimi, and Mathias Heikenwalder"]},"titleAlt":[{"title":"A five to two intermittent fasting regimen ameliorates NASH and fibrosis and blunts HCC development via hepatic PPARalpha and PCK1"}],"relHost":[{"type":{"media":"Online-Ressource","bibl":"periodical"},"title":[{"title_sort":"Cell metabolism","title":"Cell metabolism"}],"physDesc":[{"extent":"Online-Ressource"}],"id":{"eki":["477987451"],"issn":["1932-7420"],"zdb":["2174469-5"]},"pubHistory":["1.2005 -"],"disp":"A 5:2 intermittent fasting regimen ameliorates NASH and fibrosis and blunts HCC development via hepatic PPARα and PCK1Cell metabolism","origin":[{"publisher":"Elsevier ; Cell Press","dateIssuedDisp":"2005-","dateIssuedKey":"2005","publisherPlace":"Amsterdam [u.a.] ; Cambridge, Mass."}],"part":{"pages":"1371-1393.e7","issue":"6","extent":"31","volume":"36","text":"36(2024), 6 vom: Juni, Seite 1371-1393.e7","year":"2024"},"language":["eng"],"note":["Gesehen am 24.04.25"],"recId":"477987451"}],"title":[{"title":"A 5:2 intermittent fasting regimen ameliorates NASH and fibrosis and blunts HCC development via hepatic PPARα and PCK1","title_sort":"5:2 intermittent fasting regimen ameliorates NASH and fibrosis and blunts HCC development via hepatic PPARα and PCK1"}],"physDesc":[{"extent":"31 S."}],"type":{"bibl":"article-journal","media":"Online-Ressource"},"id":{"eki":["1909633208"],"doi":["10.1016/j.cmet.2024.04.015"]},"person":[{"role":"aut","given":"Suchira","family":"Gallage","display":"Gallage, Suchira"},{"display":"Ali, Sheikh Adnan","family":"Ali","given":"Sheikh Adnan","role":"aut"},{"role":"aut","given":"José Efren","family":"Barragan Avila","display":"Barragan Avila, José Efren"},{"role":"aut","given":"Nogayhan","family":"Seymen","display":"Seymen, Nogayhan"},{"role":"aut","given":"Pierluigi","family":"Ramadori","display":"Ramadori, Pierluigi"},{"display":"Joerke, Vera","family":"Joerke","given":"Vera","role":"aut"},{"given":"Laimdota","role":"aut","display":"Zizmare, Laimdota","family":"Zizmare"},{"role":"aut","given":"David","family":"Aicher","display":"Aicher, David"},{"given":"Indresh K.","role":"aut","display":"Gopalsamy, Indresh K.","family":"Gopalsamy"},{"display":"Fong, Winnie","family":"Fong","given":"Winnie","role":"aut"},{"given":"Jan","role":"aut","display":"Kosla, Jan","family":"Kosla"},{"family":"Focaccia","display":"Focaccia, Enrico","role":"aut","given":"Enrico"},{"family":"Li","display":"Li, Xin","role":"aut","given":"Xin"},{"role":"aut","given":"Suhail","family":"Yousuf","display":"Yousuf, Suhail"},{"role":"aut","given":"Tjeerd","family":"Sijmonsma","display":"Sijmonsma, Tjeerd"},{"role":"aut","given":"Mohammad","family":"Rahbari","display":"Rahbari, Mohammad"},{"given":"Katharina","role":"aut","display":"Kommoss, Katharina","family":"Kommoss"},{"given":"Adrian","role":"aut","display":"Billeter, Adrian","family":"Billeter"},{"display":"Prokosch, Sandra","family":"Prokosch","given":"Sandra","role":"aut"},{"display":"Rothermel, Ulrike","family":"Rothermel","given":"Ulrike","role":"aut"},{"display":"Mueller, Florian","family":"Mueller","given":"Florian","role":"aut"},{"display":"Hetzer, Jenny","family":"Hetzer","given":"Jenny","role":"aut"},{"display":"Heide, Danijela","family":"Heide","given":"Danijela","role":"aut"},{"role":"aut","given":"Benjamin","family":"Schinkel","display":"Schinkel, Benjamin"},{"role":"aut","given":"Tim","family":"Machauer","display":"Machauer, Tim"},{"display":"Pichler, Bernd","family":"Pichler","given":"Bernd","role":"aut"},{"given":"Nisar Peter","role":"aut","display":"Malek, Nisar Peter","family":"Malek"},{"display":"Longerich, Thomas","family":"Longerich","given":"Thomas","role":"aut"},{"given":"Susanne","role":"aut","display":"Roth, Susanne","family":"Roth"},{"family":"Rose","display":"Rose, Adam J.","role":"aut","given":"Adam J."},{"given":"Johannes","role":"aut","display":"Schwenck, Johannes","family":"Schwenck"},{"display":"Trautwein, Christoph","family":"Trautwein","given":"Christoph","role":"aut"},{"display":"Karimi, Mohammad M.","family":"Karimi","given":"Mohammad M.","role":"aut"},{"family":"Heikenwälder","display":"Heikenwälder, Mathias","role":"aut","given":"Mathias"}]} | ||
| SRT | |a GALLAGESUC52INTERMIT4202 | ||