title: A signature of renal stress resistance induced by short-term dietary restriction, fasting, and protein restriction.
abstract: During kidney transplantation, ischemia-reperfusion injury (IRI) induces oxidative stress. Short-term preoperative 30% dietary restriction (DR) and 3-day fasting protect against renal IRI. We investigated the contribution of macronutrients to this protection on both phenotypical and transcriptional levels. Male C57BL/6 mice were fed control food ad libitum, underwent two weeks of 30%DR, 3-day fasting, or received a protein-, carbohydrate- or fat-free diet for various periods of time. After completion of each diet, renal gene expression was investigated using microarrays. After induction of renal IRI by clamping the renal pedicles, animals were monitored seven days postoperatively for signs of IRI. In addition to 3-day fasting and two weeks 30%DR, three days of a protein-free diet protected against renal IRI as well, whereas the other diets did not. Gene expression patterns significantly overlapped between all diets except the fat-free diet. Detailed meta-analysis showed involvement of nuclear receptor signaling via transcription factors, including FOXO3, HNF4A and HMGA1. In conclusion, three days of a protein-free diet is sufficient to induce protection against renal IRI similar to 3-day fasting and two weeks of 30%DR. The elucidated network of common protective pathways and transcription factors further improves our mechanistic insight into the increased stress resistance induced by short-term DR.
authors.affiliation: Department of Surgery, Laboratory for Experimental Transplantation and Intestinal Surgery (LETIS), Erasmus University Medical Center, Rotterdam, the Netherlands.|Centre for Health Protection, National Institute for Public Health and the Environment, Bilthoven, the Netherlands.
authors.forename: F
authors.initials: F
authors.lastname: Jongbloed
authors.affiliation: Department of Surgery, Laboratory for Experimental Transplantation and Intestinal Surgery (LETIS), Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: T C
authors.initials: TC
authors.lastname: Saat
authors.affiliation: Department of Surgery, Laboratory for Experimental Transplantation and Intestinal Surgery (LETIS), Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Verweij
authors.affiliation: Department of Genetics, Erasmus University Medical Center, Rotterdam, the Netherlands.|Facultad de Ciencias Naturales y Matemáticas, Universidad del Rosario, Bogotá, Colombia.
authors.forename: C
authors.initials: C
authors.lastname: Payan-Gomez
authors.affiliation: Department of Genetics, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: J H J
authors.initials: JH
authors.lastname: Hoeijmakers
authors.affiliation: Department of Surgery, Laboratory for Experimental Transplantation and Intestinal Surgery (LETIS), Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: van den Engel
authors.affiliation: Centre for Health Protection, National Institute for Public Health and the Environment, Bilthoven, the Netherlands.
authors.forename: C T
authors.initials: CT
authors.lastname: van Oostrom
authors.affiliation: Department of Surgery, Laboratory for Experimental Transplantation and Intestinal Surgery (LETIS), Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: G
authors.initials: G
authors.lastname: Ambagtsheer
authors.affiliation: Centre for Health Protection, National Institute for Public Health and the Environment, Bilthoven, the Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: Imholz
authors.affiliation: Centre for Health Protection, National Institute for Public Health and the Environment, Bilthoven, the Netherlands.
authors.forename: J L A
authors.initials: JL
authors.lastname: Pennings
authors.affiliation: Centre for Health Protection, National Institute for Public Health and the Environment, Bilthoven, the Netherlands.|Department of Toxicogenetics, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: H
authors.initials: H
authors.lastname: van Steeg
authors.affiliation: Department of Surgery, Laboratory for Experimental Transplantation and Intestinal Surgery (LETIS), Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: J N M
authors.initials: JN
authors.lastname: IJzermans
authors.affiliation: Centre for Health Protection, National Institute for Public Health and the Environment, Bilthoven, the Netherlands.
authors.forename: M E T
authors.initials: ME
authors.lastname: Dollé
authors.affiliation: Department of Surgery, Laboratory for Experimental Transplantation and Intestinal Surgery (LETIS), Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: R W F
authors.initials: RW
authors.lastname: de Bruin
mesh_terms: D000818:Animals; D031204:Caloric Restriction; D018753:Diet, Protein-Restricted; D000071316:Forkhead Box Protein O3 / Q000235:genetics / Q000378:metabolism; D025741:HMGA1a Protein / Q000235:genetics / Q000378:metabolism; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D025341:Principal Component Analysis; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology; D059467:Transcriptome
chemical_list: D000071316:Forkhead Box Protein O3; C474033:FoxO3 protein, mouse; D051557:Hepatocyte Nuclear Factor 4; C496593:Hnf4a protein, mouse; D025741:HMGA1a Protein