Starvation response in mouse liver shows strong correlation with life-span-prolonging processes

Abstract

We have monitored global changes in gene expression in mouse liver in response to fasting and sugar-fed conditions using high-density microarrays. From approximately 20,000 different genes, the significantly regulated ones were grouped into specific signaling and metabolic pathways. Striking changes in lipid signaling cascade, insulin and dehydroepiandrosterone (DHEA) hormonal pathways, urea cycle and S-adenosylmethionine-based methyl transfer systems, and cell apoptosis regulators were observed. Since these pathways have been implicated to play a role in the aging process, and since we observe significant overlap of genes regulated upon starvation with those regulated upon caloric restriction, our analysis suggests that starvation may elicit a stress response that is also elicited during caloric restriction. Therefore, many of the signaling and metabolic components regulated during fasting may be the same as those which mediate caloric restriction-dependent life-span extension.

Up-Regulation of Genes Related to the Ubiquitin-Proteasome System in the Brown Adipose Tissue of 24-h-Fasted Rats

“…As expected, the genes involved in 'fatty acid beta-oxidation' were significantly up-regulated in liver of the fasted rats (Table 3), a finding in agreement with previous reports. 12,13) On the other hand, such carbohydrate metabolism-related genes as those in 'glucose catabolism' were down-regulated in BAT of the fasted animals, indicating a whole-body fuel shift from glucose to triacylglycerol during the adaptation to fasting. In all three tissues, gene expression was downregulated for many 'biosynthesis' categories, including 'lipid biosynthesis,' 'protein biosynthesis' and 'cellular biosynthesis' (Table 4).…”

“…8) The up-regulation of aquaporin9, glycerokinase, and phosphoenolpyruvatecarboxykinase in mouse liver, 9) and of PPAR in pig, mouse and rat liver have also been reported. 10,11) Although a DNA microarray analysis has been used to examine changes in the mRNA expression profiles of fasted rat WAT 12) and fasted mouse liver, 13) little is known about the expression profiles of fasted animal BAT. BAT and WAT perform opposing functions in terms of energy homeostasis.…”

Linking nutrition to genomics

“…On top of this biochemical outline, signaling components that regulate the metabolic pathways can also be identified. Using this method we have monitored global changes in gene expression in mouse liver in response to fasting and sugar-fed conditions using high density microarrays (Bauer et al, 2004).…”

Erratum: TFEB controls cellular lipid metabolism through a starvation-induced autoregulatory loop

“…The adaptive response of an organism to food deprivation is associated with major transcriptional and metabolic [1][2][3][4][5] changes and is conserved across evolution 6,7 . One of the most prominent metabolic changes observed during starvation is an increase in lipid catabolism in the liver.…”