BMAL1 functions as a cAMP-responsive coactivator of HDAC5 to regulate hepatic gluconeogenesis

Li, Jian; Lv, Sihan; Qiu, Xinchen; Yu, Junjian; Jiang, Junkun; Jin, Yalan; Guo, Wenbo; Zhao, Ruowei; Zhang, Zhenning; Zhang, Chao; Luan, Bing

doi:10.1007/s13238-018-0514-y

Cited by 11 publications

(8 citation statements)

References 16 publications

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“…Bmal1 (MGI:1096381) 5 phenotypes: Bmal1 regulates gluconeogenic gene expression by interaction with Hdac5 ( Li et al 2018 ). Bmal1 interacts with Clock to form a transcription factor complex ( Huang et al 2012 ) involved in the circadian regulation of glucose homeostasis ( Schiaffino et al 2016 ).…”

Section: Resultsmentioning

confidence: 99%

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Biochemical pathways represented by Gene Ontology-Causal Activity Models identify distinct phenotypes resulting from mutations in pathways

Hill,

Drabkin,

Smith

et al. 2023

Genetics

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Gene inactivation can affect the process(es) in which that gene acts and causally downstream ones, yielding diverse mutant phenotypes. Identifying the genetic pathways resulting in a given phenotype helps us understand how individual genes interact in a functional network. Computable representations of biological pathways include detailed process descriptions in the Reactome Knowledgebase, and causal activity flows between molecular functions in Gene Ontology-Causal Activity Models (GO-CAMs). A computational process has been developed to convert Reactome pathways to GO-CAMs. Laboratory mice are widely used models of normal and pathological human processes. We have converted human Reactome GO-CAMs to orthologous mouse GO-CAMs, as a resource to transfer pathway knowledge between humans and model organisms. These mouse GO-CAMs allowed us to define sets of genes that function in a causally connected way. To demonstrate that individual variant genes from connected pathways result in similar but distinguishable phenotypes, we used the genes in our pathway models to cross-query mouse phenotype annotations in the Mouse Genome Database (MGD). Using GO-CAM representations of two related but distinct pathways, gluconeogenesis and glycolysis, we show that individual causal paths in gene networks give rise to discrete phenotypic outcomes resulting from perturbations of glycolytic and gluconeogenic genes. The accurate and detailed descriptions of gene interactions recovered in this analysis of well-studied processes suggest that this strategy can be applied to less well-understood processes in less well-studied model systems to predict phenotypic outcomes of novel gene variants and to identify potential gene targets in altered processes.

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Section: Resultsmentioning

confidence: 99%

“…Clock (MGI:99698) 3 phenotypes: Clock and Bmal1 (above) interact to synchronize gluconeogenesis with circadian rhythms ( Schiaffino et al 2016 ; Li et al 2018 ).…”

Section: Resultsmentioning

confidence: 99%

Biochemical pathways represented by Gene Ontology-Causal Activity Models identify distinct phenotypes resulting from mutations in pathways

Hill,

Drabkin,

Smith

et al. 2023

Genetics

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“…Apart from this, the CRY KO mice exhibit increased expression of genes responsible for the hepatic gluconeogenesis and thereby increases its blood glucose concentrations [27]. Liver specific elimination of BMAL1 in the mice leads to the loss of rhythmic hepatic gene expression responsible for the glucose homeostasis and become hypoglycaemic during their fasting period [28].…”

Section: Diurnal Rhythms and Glucose Metabolism In Livermentioning

confidence: 99%

Circadian Liver Metabolism Affects Management of Type 2 Diabetes Mellitus During Cytokine Storm Due to COVID-19

Kumar

Jahan

2021

Chronobiol Med

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Diabetes is managed to keep the blood sugar in normal range. This involves liver as glucose metabolizing organ and sensitization of somatic cells to utilize this glucose for daily energy requirements. The management is subjected to the rhythmic glucose intake as diet and liver circadian cycles that runs parallel to this zeitgeber. COVID-19 patients having diabetes as comorbid condition face the challenges of inflammatory cytokine management along with the organization of glucose. Increased blood glucose level during the cytokine storm further aggravates the pathophysiology of COVID-19 patients leading to high morbidity and mortality in such patients. Clinical treatment of these patients requires multidimensional approach involving circadian variation of hepatic physiology, glucose intake, and inflammatory cytokine release.

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“…Bmal1: Clock cooperates with SREBP-1c, and downstream genes like fatty acid synthase (FASN), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), and fatty acid elongase family members (ELOVL), the low-density lipoprotein receptor (LDLr), and acetoacetyl-CoA synthetase (AACS) to modulate daily lipid metabolism in the liver (Friedrichs et al, 2018). Bmal1 can function as a cAMP-responsive coactivator of HDAC5 to regulate hepatic gluconeogenesis (Li et al, 2018). Bmal1 can drive PPARs transcription, while in turn, PPARs can activate the transcription of Bmal1, which drives PPARα and activates PPARα targeted gene expression.…”

Section: Circadian Clock Genes and Metabolism In The Setting Of Nafldmentioning

confidence: 99%

Circadian Clock Genes in the Metabolism of Non-alcoholic Fatty Liver Disease

et al. 2019

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Non-alcoholic fatty liver disease (NAFLD) is a common disease, which is characterized by the accumulation of triglycerides in the hepatocytes without excess alcohol intake. Circadian rhythms can participate in lipid, glucose, and cholesterol metabolism and are closely related to metabolism seen in this disease. Circadian clock genes can modulate liver lipid metabolism. Desynchrony of circadian rhythms and the influences imparted by external environmental stimuli can increase morbidity. By contrast, synchronizing circadian rhythms can help to alleviate the metabolic disturbance seen in NAFLD. In this review, we have discussed the current research connections that exist between the circadian clock and the metabolism of NAFLD, and we have specifically focused on the key circadian clock genes, Bmal1, Clock, Rev-Erbs, Rors, Pers, Crys, Nocturnin, and DECs.

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BMAL1 functions as a cAMP-responsive coactivator of HDAC5 to regulate hepatic gluconeogenesis

Cited by 11 publications

References 16 publications

Biochemical pathways represented by Gene Ontology-Causal Activity Models identify distinct phenotypes resulting from mutations in pathways

Biochemical pathways represented by Gene Ontology-Causal Activity Models identify distinct phenotypes resulting from mutations in pathways

Circadian Liver Metabolism Affects Management of Type 2 Diabetes Mellitus During Cytokine Storm Due to COVID-19

Circadian Clock Genes in the Metabolism of Non-alcoholic Fatty Liver Disease

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