Name	Obesity
ICD	ICD-11: 5B81

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[1]
Response Summary	Autophagy protein 5 (ATG5) and Atg7 were the targets of YTHDF2 (YTH N6-methyladenosine RNA binding protein 2). Upon FTO silencing, Atg5 and Atg7 transcripts with higher m6A levels were captured by YTHDF2, which resulted in mRNA degradation and reduction of protein expression, thus alleviating autophagy and adipogenesis.
Responsed Disease	Obesity [ICD-11: 5B81]
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Autophagy
	Adipogenesis regulation
In-vitro Model	3T3-L1	Normal	Mus musculus	CVCL_0123
	Pig primary preadipocytes (Isolated from cervical subcutaneous adipose tissue of piglets)
In-vivo Model	Mice were maintained at 22 ± 2 ℃ with a humidity of 35 ± 5% under a 12 h light and 12 h dark cycle, with free access to water and food. For the HFD experiment, female control (Ftoflox/flox) and adipose-selective fto knockout (Fabp4-Cre Ftoflox/flox, fto-AKO) mice were fed with high-fat diet (60% fat in calories; Research Diets, D12492) for the desired periods of time, and food intake and body weight were measured every week after weaning (at 3 weeks of age).
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[1]
Response Summary	Autophagy protein 5 (ATG5) and Atg7 were the targets of YTHDF2 (YTH N6-methyladenosine RNA binding protein 2). Upon FTO silencing, Atg5 and Atg7 transcripts with higher m6A levels were captured by YTHDF2, which resulted in mRNA degradation and reduction of protein expression, thus alleviating autophagy and adipogenesis.
Responsed Disease	Obesity [ICD-11: 5B81]
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Down regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Autophagy
	Adipogenesis regulation
In-vitro Model	3T3-L1	Normal	Mus musculus	CVCL_0123
	Pig primary preadipocytes (Isolated from cervical subcutaneous adipose tissue of piglets)
In-vivo Model	Mice were maintained at 22 ± 2 ℃ with a humidity of 35 ± 5% under a 12 h light and 12 h dark cycle, with free access to water and food. For the HFD experiment, female control (Ftoflox/flox) and adipose-selective fto knockout (Fabp4-Cre Ftoflox/flox, fto-AKO) mice were fed with high-fat diet (60% fat in calories; Research Diets, D12492) for the desired periods of time, and food intake and body weight were measured every week after weaning (at 3 weeks of age).

In total 4 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[2]
Response Summary	m6A-dependent Cyclin-A2 (CCNA2) and CDK2 expressions mediated by FTO and YTHDF2 contributed to EGCG-induced adipogenesis inhibition.
Responsed Disease	Obesity [ICD-11: 5B81]
Responsed Drug	Epigallocatechin gallate		Phase 3	Drug Info
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Cell cycle			hsa04110
Cell Process	Adipogenesis
In-vitro Model	3T3-L1	Normal	Mus musculus	CVCL_0123
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[2]
Response Summary	m6A-dependent Cyclin-A2 (CCNA2) and CDK2 expressions mediated by FTO and YTHDF2 contributed to EGCG-induced adipogenesis inhibition.
Responsed Disease	Obesity [ICD-11: 5B81]
Responsed Drug	Epigallocatechin gallate		Phase 3	Drug Info
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Down regulation
Cell Process	Adipogenesis
In-vitro Model	3T3-L1	Normal	Mus musculus	CVCL_0123
Experiment 3 Reporting the m6A-centered Disease Response by This Target Gene				[3]
Response Summary	FTO knockdown markedly decreased the expression of Cyclin-A2 (CCNA2) and CDK2, crucial cell cycle regulators, leading to delayed entry of MDI-induced cells into G2 phase. m6A-binding protein YTHDF2 recognized and decayed methylated mRNAs of CCNA2 and CDK2, leading to decreased protein expression, thereby prolonging cell cycle progression and suppressing adipogenesis. The adipocyte life cycle, including proliferation and adipogenesis, has become a potential target for many bioactive compounds and drugs for the prevention and treatment of obesity.
Responsed Disease	Obesity [ICD-11: 5B81]
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Down regulation
Pathway Response	Cell cycle			hsa04110
Cell Process	Adipogenesis
	Arrest cell cycle at S phase
In-vitro Model	3T3-L1	Normal	Mus musculus	CVCL_0123
Experiment 4 Reporting the m6A-centered Disease Response by This Target Gene				[3]
Response Summary	FTO knockdown markedly decreased the expression of Cyclin-A2 (CCNA2) and CDK2, crucial cell cycle regulators, leading to delayed entry of MDI-induced cells into G2 phase. m6A-binding protein YTHDF2 recognized and decayed methylated mRNAs of CCNA2 and CDK2, leading to decreased protein expression, thereby prolonging cell cycle progression and suppressing adipogenesis. The adipocyte life cycle, including proliferation and adipogenesis, has become a potential target for many bioactive compounds and drugs for the prevention and treatment of obesity.
Responsed Disease	Obesity [ICD-11: 5B81]
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Pathway Response	Cell cycle			hsa04110
Cell Process	Adipogenesis
	Arrest cell cycle at S phase
In-vitro Model	3T3-L1	Normal	Mus musculus	CVCL_0123

In total 6 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[2]
Response Summary	m6A-dependent CCNA2 and Cyclin-dependent kinase 2 (CDK2) expressions mediated by FTO and YTHDF2 contributed to EGCG-induced adipogenesis inhibition.
Responsed Disease	Obesity [ICD-11: 5B81]
Responsed Drug	Epigallocatechin gallate		Phase 3	Drug Info
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Cell cycle			hsa04110
Cell Process	Adipogenesis
In-vitro Model	3T3-L1	Normal	Mus musculus	CVCL_0123
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[2]
Response Summary	m6A-dependent CCNA2 and Cyclin-dependent kinase 2 (CDK2) expressions mediated by FTO and YTHDF2 contributed to EGCG-induced adipogenesis inhibition.
Responsed Disease	Obesity [ICD-11: 5B81]
Responsed Drug	Epigallocatechin gallate		Phase 3	Drug Info
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Down regulation
Cell Process	Adipogenesis
In-vitro Model	3T3-L1	Normal	Mus musculus	CVCL_0123
Experiment 3 Reporting the m6A-centered Disease Response by This Target Gene				[3]
Response Summary	FTO knockdown markedly decreased the expression of CCNA2 and Cyclin-dependent kinase 2 (CDK2), crucial cell cycle regulators, leading to delayed entry of MDI-induced cells into G2 phase. m6A-binding protein YTHDF2 recognized and decayed methylated mRNAs of CCNA2 and CDK2, leading to decreased protein expression, thereby prolonging cell cycle progression and suppressing adipogenesis. The adipocyte life cycle, including proliferation and adipogenesis, has become a potential target for many bioactive compounds and drugs for the prevention and treatment of obesity.
Responsed Disease	Obesity [ICD-11: 5B81]
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Down regulation
Pathway Response	Cell cycle			hsa04110
Cell Process	Adipogenesis
	Arrest cell cycle at S phase
In-vitro Model	3T3-L1	Normal	Mus musculus	CVCL_0123
Experiment 4 Reporting the m6A-centered Disease Response by This Target Gene				[3]
Response Summary	FTO knockdown markedly decreased the expression of CCNA2 and Cyclin-dependent kinase 2 (CDK2), crucial cell cycle regulators, leading to delayed entry of MDI-induced cells into G2 phase. m6A-binding protein YTHDF2 recognized and decayed methylated mRNAs of CCNA2 and CDK2, leading to decreased protein expression, thereby prolonging cell cycle progression and suppressing adipogenesis. The adipocyte life cycle, including proliferation and adipogenesis, has become a potential target for many bioactive compounds and drugs for the prevention and treatment of obesity.
Responsed Disease	Obesity [ICD-11: 5B81]
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Pathway Response	Cell cycle			hsa04110
Cell Process	Adipogenesis
	Arrest cell cycle at S phase
In-vitro Model	3T3-L1	Normal	Mus musculus	CVCL_0123
Experiment 5 Reporting the m6A-centered Disease Response by This Target Gene				[4]
Response Summary	Metformin could inhibit adipogenesis and combat obesity, metformin could inhibit protein expression of FTO, leading to increased m6A methylation levels of Ccnd1 and Cyclin-dependent kinase 2 (CDK2)(two crucial regulators in cell cycle). Ccnd1 and Cdk2 with increased m6A levels were recognised by YTHDF2, causing an YTHDF2-dependent decay and decreased protein expressions.
Responsed Disease	Obesity [ICD-11: 5B81]
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Pathway Response	Cell cycle			hsa04110
Cell Process	Cell cycle
Experiment 6 Reporting the m6A-centered Disease Response by This Target Gene				[4]
Response Summary	Metformin could inhibit adipogenesis and combat obesity, metformin could inhibit protein expression of FTO, leading to increased m6A methylation levels of Ccnd1 and Cyclin-dependent kinase 2 (CDK2)(two crucial regulators in cell cycle). Ccnd1 and Cdk2 with increased m6A levels were recognised by YTHDF2, causing an YTHDF2-dependent decay and decreased protein expressions.
Responsed Disease	Obesity [ICD-11: 5B81]
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Pathway Response	Cell cycle			hsa04110
Cell Process	Cell cycle

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[5]
Response Summary	The contribution of METTL3-mediated m6A modification of DNA damage-inducible transcript 4 protein (DDIT4) mRNA to macrophage metabolic reprogramming in non-alcoholic fatty liver disease and obesity. In METTL3-deficient macrophages, there is a significant downregulation of mammalian target of rapamycin (mTOR) and nuclear factor Kappa-B (NF-Kappa-B) pathway activity in response to cellular stress and cytokine stimulation, which can be restored by knockdown of DDIT4.
Responsed Disease	Obesity [ICD-11: 5B81]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Down regulation
Pathway Response	mTOR signaling pathway			hsa04150
	HIF-1 signaling pathway			hsa04066
In-vivo Model	The 8-10 weeks old mice were fed either a high fat diet or HF-CDAA , ad lib for 6-12 weeks. Chow diet was used as control for HFD.The mouse liver was perfused with PBS through portal vein, and liver tissue was cut into small pieces by a scissor. The single cell was made using syringe plunger to mull the tissue, and passed through a 40 uM cell strainer.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[6]
Response Summary	FTO regulates hepatic lipogenesis via FTO-dependent m6A demethylation in Fatty acid synthase (FASN) mRNA and indicate the critical role of FTO-mediated lipid metabolism in the survival of HepG2 cells. This study provides novel insights into a unique RNA epigenetic mechanism by which FTO mediates hepatic lipid accumulation through m6 A modification and indicates that FTO could be a potential target for obesity-related diseases and cancer.
Responsed Disease	Obesity [ICD-11: 5B81]
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Target Regulation	Down regulation
Cell Process	Deficiency of lipid accumulation
	Cellular apoptosis
In-vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens	CVCL_0027

In total 4 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[7]
Response Summary	Obesity is becoming a global problem. ZFP217 knockdown-induced adipogenesis inhibition was caused by G1/S-specific cyclin-D1 (CCND1), which was mediated by METTL3 and YTHDF2 in an m6A-dependent manner.
Responsed Disease	Obesity [ICD-11: 5B81]
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Down regulation
Pathway Response	Cell cycle			hsa04110
Cell Process	Mitotic clonal
	Prolonged G1/S transition
In-vitro Model	3T3-L1	Normal	Mus musculus	CVCL_0123
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[7]
Response Summary	Obesity is becoming a global problem. ZFP217 knockdown-induced adipogenesis inhibition was caused by G1/S-specific cyclin-D1 (CCND1), which was mediated by METTL3 and YTHDF2 in an m6A-dependent manner.
Responsed Disease	Obesity [ICD-11: 5B81]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Cell cycle			hsa04110
Cell Process	Mitotic clonal
	Prolonged G1/S transition
In-vitro Model	3T3-L1	Normal	Mus musculus	CVCL_0123
Experiment 3 Reporting the m6A-centered Disease Response by This Target Gene				[4]
Response Summary	Metformin could inhibit adipogenesis and combat obesity, metformin could inhibit protein expression of FTO, leading to increased m6A methylation levels of G1/S-specific cyclin-D1 (CCND1) and Cdk2(two crucial regulators in cell cycle). Ccnd1 and Cdk2 with increased m6A levels were recognised by YTHDF2, causing an YTHDF2-dependent decay and decreased protein expressions.
Responsed Disease	Obesity [ICD-11: 5B81]
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Pathway Response	Cell cycle			hsa04110
Cell Process	Cell cycle
Experiment 4 Reporting the m6A-centered Disease Response by This Target Gene				[4]
Response Summary	Metformin could inhibit adipogenesis and combat obesity, metformin could inhibit protein expression of FTO, leading to increased m6A methylation levels of G1/S-specific cyclin-D1 (CCND1) and Cdk2(two crucial regulators in cell cycle). Ccnd1 and Cdk2 with increased m6A levels were recognised by YTHDF2, causing an YTHDF2-dependent decay and decreased protein expressions.
Responsed Disease	Obesity [ICD-11: 5B81]
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Pathway Response	Cell cycle			hsa04110
Cell Process	Cell cycle

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[5]
Response Summary	The contribution of METTL3-mediated m6A modif ication of Ddit4 mRNA to macrophage metabolic reprogramming in non-alcoholic fatty liver disease and obesity. In METTL3-deficient macrophages, there is a significant downregulation of mammalian target of rapamycin (mTOR) and Nuclear factor NF-kappa-B p105 subunit (NF-Kappa-B/NFKB1) pathway activity in response to cellular stress and cytokine stimulation, which can be restored by knockdown of DDIT4.
Responsed Disease	Obesity [ICD-11: 5B81]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	mTOR signaling pathway			hsa04150
	HIF-1 signaling pathway			hsa04066
In-vivo Model	The 8-10 weeks old mice were fed either a high fat diet or HF-CDAA , ad lib for 6-12 weeks. Chow diet was used as control for HFD.The mouse liver was perfused with PBS through portal vein, and liver tissue was cut into small pieces by a scissor. The single cell was made using syringe plunger to mull the tissue, and passed through a 40 uM cell strainer.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[5]
Response Summary	The contribution of Nuclear factor NF-kappa-B p105 subunit (NF-Kappa-B/NFKB1)-mediated m6A modification of Ddit4 mRNA to macrophage metabolic reprogramming in non-alcoholic fatty liver disease and obesity. In METTL3-deficient macrophages, there is a significant downregulation of mammalian target of rapamycin (mTOR) and Nuclear factor NF-kappa-B p105 subunit (NF-Kappa-B/NFKB1) pathway activity in response to cellular stress and cytokine stimulation, which can be restored by knockdown of DDIT4.
Responsed Disease	Obesity [ICD-11: 5B81]
Target Regulator	Methyltransferase-like 3 (METTL3)		WRITER	Regulator Info
Target Regulation	Up regulation
Pathway Response	mTOR signaling pathway			hsa04150
	HIF-1 signaling pathway			hsa04066
In-vivo Model	The 8-10 weeks old mice were fed either a high fat diet or HF-CDAA , ad lib for 6-12 weeks. Chow diet was used as control for HFD.The mouse liver was perfused with PBS through portal vein, and liver tissue was cut into small pieces by a scissor. The single cell was made using syringe plunger to mull the tissue, and passed through a 40 uM cell strainer.

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[8]
Response Summary	FTO-dependent m7A demethylation functions as a novel regulatory mechanism of RNA processing and plays a critical role in the regulation of adipogenesis and obesity. FTO-dependent regulatory role of m6A and SRSF2 in mRNA splicing and adipocyte differentiation. FTO controls exonic splicing of adipogenic regulatory factor Protein CBFA2T1 (RUNX1T1) by regulating m6A levels around splice sites and thereby modulates differentiation.
Responsed Disease	Obesity [ICD-11: 5B81]
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Target Regulation	Down regulation
Cell Process	adipogenesis
	Spliceosome (hsa03040)
In-vitro Model	3T3-L1	Normal	Mus musculus	CVCL_0123

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[8]
Response Summary	FTO-dependent m7A demethylation functions as a novel regulatory mechanism of RNA processing and plays a critical role in the regulation of adipogenesis and obesity. FTO-dependent regulatory role of m6A and SRSF protein kinase 2 (SRPK2) in mRNA splicing and adipocyte differentiation. FTO controls exonic splicing of adipogenic regulatory factor RUNX1T1 by regulating m6A levels around splice sites and thereby modulates differentiation.
Responsed Disease	Obesity [ICD-11: 5B81]
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Target Regulation	Down regulation
Pathway Response	Spliceosome			hsa03040
Cell Process	adipogenesis
In-vitro Model	3T3-L1	Normal	Mus musculus	CVCL_0123

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[9]
Response Summary	m6A-dependent TNF receptor-associated factor 4 (TRAF4) expression upregulation by ALKBH5 and YTHDF1 contributes to curcumin-induced obesity prevention.
Responsed Disease	Obesity [ICD-11: 5B81]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Ubiquitin mediated proteolysis			hsa04120), Proteasome
Cell Process	Ubiquitination degradation
In-vitro Model	SVF (Stromal vascular cell fraction (SVF) was isolated from minced inguinal adipose tissue of male C57BL/6J mice (3-4 weeks old))
	3T3-L1	Normal	Mus musculus	CVCL_0123
In-vivo Model	Before the tests, animals were fasted for 8 h. l glucose tolerance test (GTT) was conducted during week 11 on the diet. The mice were challenged with 2 g/kg body weight d-glucose (Sigma-Aldrich, USA). Insulin tolerance test (ITT) was conducted during week 12 on the diet. For insulin tolerance test, mice were injected intraperitoneally with 0.75 U/kg body weight insulin (Sigma-Aldrich, USA). For both tests, blood samples were taken from the tail vein and glucose levels were measured at indicated time points after administration using an AlphaTRAK glucometer
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[9]
Response Summary	m6A-dependent TNF receptor-associated factor 4 (TRAF4) expression upregulation by ALKBH5 and YTHDF1 contributes to curcumin-induced obesity prevention.
Responsed Disease	Obesity [ICD-11: 5B81]
Target Regulator	YTH domain-containing family protein 1 (YTHDF1)		READER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Ubiquitin mediated proteolysis			hsa04120), Proteasome
Cell Process	Ubiquitination degradation
In-vitro Model	SVF (Stromal vascular cell fraction (SVF) was isolated from minced inguinal adipose tissue of male C57BL/6J mice (3-4 weeks old))
	3T3-L1	Normal	Mus musculus	CVCL_0123
In-vivo Model	Before the tests, animals were fasted for 8 h. l glucose tolerance test (GTT) was conducted during week 11 on the diet. The mice were challenged with 2 g/kg body weight d-glucose (Sigma-Aldrich, USA). Insulin tolerance test (ITT) was conducted during week 12 on the diet. For insulin tolerance test, mice were injected intraperitoneally with 0.75 U/kg body weight insulin (Sigma-Aldrich, USA). For both tests, blood samples were taken from the tail vein and glucose levels were measured at indicated time points after administration using an AlphaTRAK glucometer

In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[1]
Response Summary	Atg5 and Ubiquitin-like modifier-activating enzyme ATG7 (ATG7) were the targets of YTHDF2 (YTH N6-methyladenosine RNA binding protein 2). Upon FTO silencing, Atg5 and Atg7 transcripts with higher m6A levels were captured by YTHDF2, which resulted in mRNA degradation and reduction of protein expression, thus alleviating autophagy and adipogenesis.
Responsed Disease	Obesity [ICD-11: 5B81]
Target Regulator	Fat mass and obesity-associated protein (FTO)		ERASER	Regulator Info
Target Regulation	Up regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Autophagy
	Adipogenesis regulation
In-vitro Model	3T3-L1	Normal	Mus musculus	CVCL_0123
	Pig primary preadipocytes (Isolated from cervical subcutaneous adipose tissue of piglets)
In-vivo Model	Mice were maintained at 22 ± 2 ℃ with a humidity of 35 ± 5% under a 12 h light and 12 h dark cycle, with free access to water and food. For the HFD experiment, female control (Ftoflox/flox) and adipose-selective fto knockout (Fabp4-Cre Ftoflox/flox, fto-AKO) mice were fed with high-fat diet (60% fat in calories; Research Diets, D12492) for the desired periods of time, and food intake and body weight were measured every week after weaning (at 3 weeks of age).
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene				[1]
Response Summary	Atg5 and Ubiquitin-like modifier-activating enzyme ATG7 (ATG7) were the targets of YTHDF2 (YTH N6-methyladenosine RNA binding protein 2). Upon FTO silencing, Atg5 and Atg7 transcripts with higher m6A levels were captured by YTHDF2, which resulted in mRNA degradation and reduction of protein expression, thus alleviating autophagy and adipogenesis.
Responsed Disease	Obesity [ICD-11: 5B81]
Target Regulator	YTH domain-containing family protein 2 (YTHDF2)		READER	Regulator Info
Target Regulation	Down regulation
Pathway Response	Autophagy			hsa04140
Cell Process	Autophagy
	Adipogenesis regulation
In-vitro Model	3T3-L1	Normal	Mus musculus	CVCL_0123
	Pig primary preadipocytes (Isolated from cervical subcutaneous adipose tissue of piglets)
In-vivo Model	Mice were maintained at 22 ± 2 ℃ with a humidity of 35 ± 5% under a 12 h light and 12 h dark cycle, with free access to water and food. For the HFD experiment, female control (Ftoflox/flox) and adipose-selective fto knockout (Fabp4-Cre Ftoflox/flox, fto-AKO) mice were fed with high-fat diet (60% fat in calories; Research Diets, D12492) for the desired periods of time, and food intake and body weight were measured every week after weaning (at 3 weeks of age).

Ref 1	m(6)A mRNA methylation controls autophagy and adipogenesis by targeting Atg5 and Atg7. Autophagy. 2020 Jul;16(7):1221-1235. doi: 10.1080/15548627.2019.1659617. Epub 2019 Aug 26.
Ref 2	Epigallocatechin gallate targets FTO and inhibits adipogenesis in an mRNA m(6)A-YTHDF2-dependent manner. Int J Obes (Lond). 2018 Jul;42(7):1378-1388. doi: 10.1038/s41366-018-0082-5. Epub 2018 May 24.
Ref 3	FTO regulates adipogenesis by controlling cell cycle progression via m(6)A-YTHDF2 dependent mechanism. Biochim Biophys Acta Mol Cell Biol Lipids. 2018 Oct;1863(10):1323-1330. doi: 10.1016/j.bbalip.2018.08.008. Epub 2018 Aug 13.
Ref 4	Metformin combats obesity by targeting FTO in an m(6)A-YTHDF2-dependent manner. J Drug Target. 2022 May 9:1-9. doi: 10.1080/1061186X.2022.2071906. Online ahead of print.
Ref 5	m(6)A mRNA methylation-directed myeloid cell activation controls progression of NAFLD and obesity. Cell Rep. 2021 Nov 9;37(6):109968. doi: 10.1016/j.celrep.2021.109968.
Ref 6	Fat mass and obesity-associated protein regulates lipogenesis via m(6) A modification in fatty acid synthase mRNA. Cell Biol Int. 2021 Feb;45(2):334-344. doi: 10.1002/cbin.11490. Epub 2020 Nov 8.
Ref 7	ZFP217 regulates adipogenesis by controlling mitotic clonal expansion in a METTL3-m(6)A dependent manner. RNA Biol. 2019 Dec;16(12):1785-1793. doi: 10.1080/15476286.2019.1658508. Epub 2019 Aug 27.
Ref 8	FTO-dependent demethylation of N6-methyladenosine regulates mRNA splicing and is required for adipogenesis. Cell Res. 2014 Dec;24(12):1403-19. doi: 10.1038/cr.2014.151. Epub 2014 Nov 21.
Ref 9	Curcumin prevents obesity by targeting TRAF4-induced ubiquitylation in m(6) A-dependent manner. EMBO Rep. 2021 May 5;22(5):e52146. doi: 10.15252/embr.202052146. Epub 2021 Apr 20.