m6A-centered Disease Response Information

General Information of the Disease (ID: M6ADIS0086)
Name
Metabolic disorders
ICD
ICD-11: 5D2Z
Full List of Target Gene(s) of This m6A-centered Disease Response
Brain and muscle ARNT-like 1 (Bmal1/ARNTL)
 Target Info 
In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [1]
Response Summary PPaRalpha to mediate its mRNA stability to regulate lipid metabolism. Hepatic deletion of Brain and muscle ARNT-like 1 (Bmal1/ARNTL) increases m6A mRNA methylation, particularly of PPaRalpha. Inhibition of m6A methylation via knockdown of m6A methyltransferase METTL3 decreases PPaR-Alpha m6A abundance and increases PPaRalpha mRNA lifetime and expression, reducing lipid accumulation in cells in vitro. YTHDF2 binds to PPaRalpha to mediate its mRNA stability to regulate lipid metabolism. Transcriptional regulation of circadian rhythms is essential for lipid metabolic homeostasis, disruptions of which can lead to metabolic diseases.
Responsed Disease Metabolic disorders [ICD-11: 5D2Z]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response Adipocytokine signaling pathway hsa04920
Cell Process Llipid metabolism
In-vitro Model Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
Hepa 1-6 Hepatocellular carcinoma of the mouse Mus musculus CVCL_0327
In-vivo Model Liver-specific Bmal1f/f-AlbCre-knockout mice were purchased from Jackson Laboratory. C57BI/6J or Bmal1f/f-AlbCre-knockout male mice were maintained under a 12 hr light/12 hr dark (LD) cycle (ZT0 = 6 AM) and fed ad libitum with normal rodent chow (2018 Global 18% Protein diet, Envigo) and water. At 10-14 weeks of age, 10 male mice per group were sacrificed via CO2 asphyxiation at Zeitgeber Time (ZT) 0,2,6,10,12,14,18,22. In order to induce high levels of ROS in the liver, WT male mice were fasted 12 h and followed by intraperitoneal injection with 300 mg/kg APAP dissolved in PBS and re-fed.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene [1]
Response Summary PPaRalpha to mediate its mRNA stability to regulate lipid metabolism. Hepatic deletion of Brain and muscle ARNT-like 1 (Bmal1/ARNTL) increases m6A mRNA methylation, particularly of PPaRalpha. Inhibition of m6A methylation via knockdown of m6A methyltransferase METTL3 decreases PPaR-Alpha m6A abundance and increases PPaRalpha mRNA lifetime and expression, reducing lipid accumulation in cells in vitro. YTHDF2 binds to PPaRalpha to mediate its mRNA stability to regulate lipid metabolism. Transcriptional regulation of circadian rhythms is essential for lipid metabolic homeostasis, disruptions of which can lead to metabolic diseases.
Responsed Disease Metabolic disorders [ICD-11: 5D2Z]
Target Regulator YTH domain-containing family protein 2 (YTHDF2) READER
 Regulator Info 
Target Regulation Down regulation
Pathway Response PPAR signaling pathway hsa03320
Adipocytokine signaling pathway hsa04920
Cell Process Llipid metabolism
In-vitro Model Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
Hepa 1-6 Hepatocellular carcinoma of the mouse Mus musculus CVCL_0327
In-vivo Model Liver-specific Bmal1f/f-AlbCre-knockout mice were purchased from Jackson Laboratory. C57BI/6J or Bmal1f/f-AlbCre-knockout male mice were maintained under a 12 hr light/12 hr dark (LD) cycle (ZT0 = 6 AM) and fed ad libitum with normal rodent chow (2018 Global 18% Protein diet, Envigo) and water. At 10-14 weeks of age, 10 male mice per group were sacrificed via CO2 asphyxiation at Zeitgeber Time (ZT) 0,2,6,10,12,14,18,22. In order to induce high levels of ROS in the liver, WT male mice were fasted 12 h and followed by intraperitoneal injection with 300 mg/kg APAP dissolved in PBS and re-fed.
Peroxisome proliferator-activated receptor alpha (PPARalpha/PPARA)
 Target Info 
In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [1]
Response Summary PPaRalpha to mediate its mRNA stability to regulate lipid metabolism. Hepatic deletion of Bmal1 increases m6A mRNA methylation, particularly of Peroxisome proliferator-activated receptor alpha (PPARalpha/PPARA). Inhibition of m6A methylation via knockdown of m6A methyltransferase METTL3 decreases PPaR-Alpha m6A abundance and increases PPaRalpha mRNA lifetime and expression, reducing lipid accumulation in cells in vitro. YTHDF2 binds to PPaRalpha to mediate its mRNA stability to regulate lipid metabolism. Transcriptional regulation of circadian rhythms is essential for lipid metabolic homeostasis, disruptions of which can lead to metabolic diseases.
Responsed Disease Metabolic disorders [ICD-11: 5D2Z]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Down regulation
Pathway Response PPAR signaling pathway hsa03320
Adipocytokine signaling pathway hsa04920
Cell Process Llipid metabolism
In-vitro Model Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
Hepa 1-6 Hepatocellular carcinoma of the mouse Mus musculus CVCL_0327
In-vivo Model Liver-specific Bmal1f/f-AlbCre-knockout mice were purchased from Jackson Laboratory. C57BI/6J or Bmal1f/f-AlbCre-knockout male mice were maintained under a 12 hr light/12 hr dark (LD) cycle (ZT0 = 6 AM) and fed ad libitum with normal rodent chow (2018 Global 18% Protein diet, Envigo) and water. At 10-14 weeks of age, 10 male mice per group were sacrificed via CO2 asphyxiation at Zeitgeber Time (ZT) 0,2,6,10,12,14,18,22. In order to induce high levels of ROS in the liver, WT male mice were fasted 12 h and followed by intraperitoneal injection with 300 mg/kg APAP dissolved in PBS and re-fed.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene [1]
Response Summary PPaRalpha to mediate its mRNA stability to regulate lipid metabolism. Hepatic deletion of Bmal1 increases m6A mRNA methylation, particularly of Peroxisome proliferator-activated receptor alpha (PPARalpha/PPARA). Inhibition of m6A methylation via knockdown of m6A methyltransferase METTL3 decreases PPaR-Alpha m6A abundance and increases PPaRalpha mRNA lifetime and expression, reducing lipid accumulation in cells in vitro. YTHDF2 binds to PPaRalpha to mediate its mRNA stability to regulate lipid metabolism. Transcriptional regulation of circadian rhythms is essential for lipid metabolic homeostasis, disruptions of which can lead to metabolic diseases.
Responsed Disease Metabolic disorders [ICD-11: 5D2Z]
Target Regulator YTH domain-containing family protein 2 (YTHDF2) READER
 Regulator Info 
Target Regulation Down regulation
Pathway Response PPAR signaling pathway hsa03320
Adipocytokine signaling pathway hsa04920
Cell Process Llipid metabolism
In-vitro Model Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
Hepa 1-6 Hepatocellular carcinoma of the mouse Mus musculus CVCL_0327
In-vivo Model Liver-specific Bmal1f/f-AlbCre-knockout mice were purchased from Jackson Laboratory. C57BI/6J or Bmal1f/f-AlbCre-knockout male mice were maintained under a 12 hr light/12 hr dark (LD) cycle (ZT0 = 6 AM) and fed ad libitum with normal rodent chow (2018 Global 18% Protein diet, Envigo) and water. At 10-14 weeks of age, 10 male mice per group were sacrificed via CO2 asphyxiation at Zeitgeber Time (ZT) 0,2,6,10,12,14,18,22. In order to induce high levels of ROS in the liver, WT male mice were fasted 12 h and followed by intraperitoneal injection with 300 mg/kg APAP dissolved in PBS and re-fed.
References
Ref 1 Circadian Clock Regulation of Hepatic Lipid Metabolism by Modulation of m(6)A mRNA Methylation. Cell Rep. 2018 Nov 13;25(7):1816-1828.e4. doi: 10.1016/j.celrep.2018.10.068.