Salt-inducible Kinase 3 Signaling Is Important for the Gluconeogenic Programs in Mouse Hepatocytes

Itoh, Yumi; Sanosaka, Masato; Fuchino, Hiroyuki; Yahara, Yasuhito; Kumagai, Akira; Takemoto, Daisaku; Kagawa, Mai; Doi, Junko; Ohta, Miho; Tsumaki, Noriyuki; Kawahara, Nobuo; Takemori, Hiroshi

doi:10.1074/jbc.m115.640821

Cited by 49 publications

(62 citation statements)

References 54 publications

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“…We sought to identify molecular signals that mediate this metabolic regulation of sleep. Because SIK3 is a key regulator of sleep [27] and metabolism [34, 51, 52], we reasoned that SIKs may coordinate both metabolism and behavioral state (sleep/wake). In contrast to mammals or Drosophila , which have three or two genes respectively encoding SIK proteins, C. elegans has only one called KIN-29 (S2A Fig ) thereby simplifying genetic manipulations.…”

Section: Resultsmentioning

confidence: 99%

A salt-induced kinase (SIK) is required for the metabolic regulation of sleep

Grubbs

Lopes

Linden

et al. 2019

Preprint

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ABSTRACTMany lines of evidence point to links between sleep regulation and energy homeostasis, but mechanisms underlying these connections are unknown. During C. elegans sleep, energetic stores are allocated to non-neural tasks with a resultant drop in the overall fat stores and energy charge. Mutants lacking KIN-29, the C. elegans homolog of a mammalian Salt-Inducible Kinase (SIK) that signals sleep pressure, have low ATP levels despite high fat stores, indicating a defective response to cellular energy deficits. Liberating energy stores corrects adiposity and sleep defects of kin-29 mutants. kin-29 sleep and energy homeostasis roles map to a small number of sensory neurons that act upstream of fat regulation as well as of central sleep-controlling neurons, suggesting hierarchical somatic/neural interactions regulating sleep and energy homeostasis. Genetic interaction between kin-29 and the histone deacetylase hda-4 coupled with subcellular localization studies indicate that KIN-29 acts in the nucleus to regulate sleep. We propose that KIN-29/SIK acts in nuclei of sensory neuroendocrine cells to transduce low cellular energy charge into the mobilization of energy stores, which in turn promotes sleep.HighlightsSleep is associated with fat mobilization and low ATP levelsMetabolic regulation of sleep requires the salt-induced kinase (SIK) homolog KIN-29KIN-29 acts in sensory neurons upstream of sleep-promoting neuronsNuclear localization of KIN-29 is required for the metabolic regulation of sleepA type 2 histone deacetylase acts down stream of KIN-29 in the regulation of sleep.Liberation of energy from fat-storage cells promotes sleep.Beta-oxidation promotes sleep.

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Section: Resultsmentioning

confidence: 99%

A salt-induced kinase (SIK) is required for the metabolic regulation of sleep

Grubbs

Lopes

Linden

et al. 2019

Preprint

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“…In C. elegans, mutation of the SIK3 orthologue, kin-29, has been linked to small body size [30], and in Drosophila, SIK3 has been linked to regulation of lipid metabolism [31], regulation of energy balance [32], and maintenance of glucose tolerance [33]. Sik3 -/mice display lipodystrophy, hypolipidemia, hypoglycemia, and hyper-insulin sensitivity [34,35]. Moreover, the lack of Sik3 in mice was linked to reduced energy storage, and resistance to weight gain from a high-fat diet [34].…”

Section: Discussionmentioning

confidence: 99%

The derived allele of a novel intergenic variant at chromosome 11 associates with lower body mass index and a favorable metabolic phenotype in Greenlanders

et al. 2020

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The genetic architecture of the small and isolated Greenlandic population is advantageous for identification of novel genetic variants associated with cardio-metabolic traits. We aimed to identify genetic loci associated with body mass index (BMI), to expand the knowledge of the genetic and biological mechanisms underlying obesity. Stage 1 BMI-association analyses were performed in 4,626 Greenlanders. Stage 2 replication and meta-analysis were performed in additional cohorts comprising 1,058 Yup'ik Alaska Native people, and 1,529 Greenlanders. Obesity-related traits were assessed in the stage 1 study population. We identified a common variant on chromosome 11, rs4936356, where the derived G-allele had a frequency of 24% in the stage 1 study population. The derived allele was genome-wide significantly associated with lower BMI (beta (SE), -0.14 SD (0.03), p = 3.2x10 -8 ), corresponding to 0.64 kg/m 2 lower BMI per G allele in the stage 1 study population. We observed a similar effect in the Yup'ik cohort (-0.09 SD, p = 0.038), and a non-significant effect in the same direction in the independent Greenlandic stage 2 cohort (-0.03 SD, p = 0.514). The

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“…All use of hES cells was approved by the ethical review board at our institute and adhered to the guidelines from the Japanese Ministries. Because hepatic cells are helpful to examine nutritional responses, the mouse hepatoma cell line AML‐12 was obtained from American Type Culture Collection (Manassas, VA, http://www.atcc.org) and was maintained as previously described [2, 16, 19].…”

Section: Methodsmentioning

confidence: 99%

A Simple Method for Labeling Human Embryonic Stem Cells Destined to Lose Undifferentiated Potency

Kumagai

Suga

Yanagihara

et al. 2016

Stem Cells Translational Medicine

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Mitochondrial oxidative phosphorylation is a major source of cellular ATP. Its usage as an energy source varies, not only according to the extracellular environment, but also during development and differentiation, as indicated by the reported changes in the flux ratio of glycolysis to oxidative phosphorylation during embryonic stem (ES) cell differentiation. The fluorescent probe JC-1 allows visualization of changes in the mitochondrial membrane potential produced by oxidative phosphorylation. Strong JC-1 signals were localized in the differentiated cells located at the edge of H9 ES colonies that expressed vimentin, an early differentiation maker. The JC-1 signals were further intensified when individual adjacent colonies were in contact with each other. Time-lapse analyses revealed that JC-1-labeled H9 cells under an overconfluent condition were highly differentiated after subculture, suggesting that monitoring oxidative phosphorylation in live cells might facilitate the prediction of induced pluripotent stem cells, as well as ES cells, that are destined to lose their undifferentiated potency.

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Salt-inducible Kinase 3 Signaling Is Important for the Gluconeogenic Programs in Mouse Hepatocytes

Cited by 49 publications

References 54 publications

A salt-induced kinase (SIK) is required for the metabolic regulation of sleep

A salt-induced kinase (SIK) is required for the metabolic regulation of sleep

The derived allele of a novel intergenic variant at chromosome 11 associates with lower body mass index and a favorable metabolic phenotype in Greenlanders

A Simple Method for Labeling Human Embryonic Stem Cells Destined to Lose Undifferentiated Potency

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