Short-term dietary restriction and fasting precondition against ischemia reperfusion injury in mice.
Dietary restriction (DR) extends lifespan and increases resistance to multiple forms of stress, including ischemia reperfusion injury to the brain and heart in rodents. While maximal effects on lifespan require long-term restriction, the kinetics of onset of benefits against acute stress is not known. Here, we show that 2-4 weeks of 30% DR improved survival and kidney function following renal ischemia reperfusion injury in mice. Brief periods of water-only fasting were similarly effective at protecting against ischemic damage. Significant protection occurred within 1 day, persisted for several days beyond the fasting period and extended to another organ, the liver. Protection by both short-term DR and fasting correlated with improved insulin sensitivity, increased expression of markers of antioxidant defense and reduced expression of markers of inflammation and insulin/insulin-like growth factor-1 signaling. Unbiased transcriptional profiling of kidneys from mice subject to short-term DR or fasting revealed a significant enrichment of signature genes of long-term DR. These data demonstrate that brief periods of reduced food intake, including short-term daily restriction and fasting, can increase resistance to ischemia reperfusion injury in rodents and suggest a rapid onset of benefits of DR in mammals.
Mitchell
James R
JR
Department of Genetics, Erasmus Medical Center, Cancer Genomics Center, Dr. Molewaterplein 50, 3015 GE, Rotterdam, The Netherlands. jmitchel@hsph.harvard.edu
Verweij
Mariëlle
M
Brand
Karl
K
van de Ven
Marieke
M
Goemaere
Natascha
N
van den Engel
Sandra
S
Chu
Timothy
T
Forrer
Flavio
F
Müller
Cristina
C
de Jong
Marion
M
van IJcken
Wilfred
W
IJzermans
Jan N M
JN
Hoeijmakers
Jan H J
JH
de Bruin
Ron W F
RW
D000818:Animals; D031204:Caloric Restriction; D005215:Fasting; D005786:Gene Expression Regulation; D007328:Insulin / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007674:Kidney Diseases / Q000178:diet therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D007677:Kidney Function Tests; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D015427:Reperfusion Injury / Q000178:diet therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D015398:Signal Transduction; D015996:Survival Rate; D013997:Time Factors; D014158:Transcription, Genetic
D007328:Insulin; D007334:Insulin-Like Growth Factor I