Data of RNA-seq transcriptomes of liver, bone, heart, kidney and blood in klotho mice at a pre-symptomatic state and the effect of a traditional Japanese multi-herbal medicine, juzentaihoto

Okada, Norihiro; Oshima, Koichiro; Iwasaki, Yoshiaki; Maruko, Akiko; Matsumura, Kenya; Iioka, Erica; Vu, Trieu-Duc; Fujitsuka, Naoki; Nishi, Akinori; Sugiyama, Aiko; Nishiyama, Mitsue; Kaneko, Atsushi; Mizoguchi, Kazuo; Yamamoto, Masahiro; Nishimura, Susumu

doi:10.1016/j.dib.2022.108197

Cited by 3 publications

(7 citation statements)

References 15 publications

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“…Therefore, we hypothesized that gluconeogenesis is activated in klotho mice (Hatting et al, 2018; see below). This is consistent with other metabolomics data showing that several glycolytic intermediates such as glucose 1-phosphate, fructose 1,6-diphosphate, and dihydroxyacetone phosphate are lower in KL‒ mice than in WT mice (Okada et al, 2022), suggesting that glycolysis is generally repressed in the liver of KL‒ mice. Consistent with these observations, the abundance of free amino acids such as Arg and Gly were found to be lower in KL‒ mice compared with WT mice (Okada et al, 2022), suggesting that the AMPK pathway is activated and that the mTOR pathway is repressed (see below).…”

Section: Resultssupporting

confidence: 92%

“…We have previously reported that KL‒ mice are in a state that mimicks starvation, based on the fact that these mice have elevated levels of 3-hydroxybutylic acid, one of the ketone bodies (Okada et al, 2021, 2022). Therefore, we hypothesized that gluconeogenesis is activated in klotho mice (Hatting et al, 2018; see below).…”

Section: Resultsmentioning

confidence: 99%

“…Second, here are the data of metabolomic analysis. Initially, it was shown that the mice were under pseudo-starvation conditions because their 3-hydroxybuthylic acid (ketone bodies) was elevated and it was observed that JTT administration slightly, but not significantly, reduced these ketones (Okada et al 2021, 2022). This seems to indicate a slight improvement in the energy status of the liver cells.…”

Section: Discussionmentioning

confidence: 99%

“…Heme is synthesized in eight steps using glycine and succinyl-CoA as starting materials, and four of the eight enzymes were found to be 2- to 5-fold more transcribed by JTT (Okada et al, 2022). Since heme is known to be a cofactor for many mitochondrial enzymes (Kim et al, 2012), this may also lead to mitochondrial activation (Okada et al 2022). Indeed, several enzymes of the mitochondrial complex V (e.g., Atp5a1, Atp5b, Atp5d, etc.)…”

Section: Discussionmentioning

confidence: 99%

“…The cause of the lower blood glucose levels in the mutant mice may be due to the suppression of nutrient uptake in the intestine despite an adequate dietary intake (Asuzu et al, 2011). Because the effects of hypoglycemia are systemic and not limited to the blood, we wondered if the pseudo-starvation state (i.e., hypoglycemia) of klotho mice might underlie the excessive IR observed in several organs of these mice (Okada et al, 2021, 2022).…”

Section: Introductionmentioning

confidence: 99%

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A potential pathway that links intron retention with the physiological recovery by a Japanese herbal medicine

Okada,

Oshima,

Maruko

et al. 2023

Preprint

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Our previous experiments with klotho mice (i.e., klotho knockout mice) showed that aberrant intron retention (IR) occurs in a pre-symptomatic state of aging and can be restored to the normal state by administration of Juzentaihoto (JTT), a formula of the Japanese herbal medicine (referred to as kampo; Okada et al., 2021). To explain that this phenomenon is not just a specific example observed in klotho mice, but is due to a universal cause that may be common in a pre-symptomatic state, we re-analyzed the data for genes that were differentially expressed in the klotho liver in response to JTT. Our data showed that AMPK signaling was activated in these mice, resulting in inhibition of anabolic pathways including protein synthesis and activation of catabolic pathways including lipolysis in various organs. These data were consistent with the observation that klotho mice appeared to be in a perpetual state of pseudo-starvation, i.e., based on their overall metabolic profile. The abnormally increased incidence of IR (IncIR) in the liver of klotho mice could be classified into three types according to their transcriptional status, revealing that each of all the three types of IncIR was caused by AMPK activation, a consequence of the pseudo-starvation state exhibited by these mice. Furthermore, we showed that both the transcriptional drift variance and the IR drift variance can be useful for visually assessing recovery from the pseudo-starvation state of klotho mice after administration of JTT. With these data, we propose a novel pathway linking intron retention to changes in the physiological state such as starvation, resulting in the maintenance of cellular homeostasis.

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Section: Resultssupporting

confidence: 92%