Table 2 Open in new tab Correlation...

Table 2

Correlation analysis of EAT GIPR and EAT GCGR with genes involved in FFA metabolism and adipogenesis

Glucose-dependent insulinotropic peptide receptor (GIPR)
a) Fatty acid metabolism genes and glucose-dependent insulinotropic peptide receptor (GIPR)
Genes	Family group	Function	Correlation coefficient	P value
ACAD11	Acetyl-CoA dehydrogenases	Promote FFA oxidation	−0.7507	<0.0001
ACADS			−0.5371	0.0013
ACADVL			−0.5531	0.0008
ACADM			−0.5551	0.0008
ACAD9			−0.5899	0.0003
ACSBG1	Acyl-CoA synthetases	Activate long- and medium-chain FFA for oxidation	−0.3797	0.0293
ACSBG2			0.6129	0.0001
ACSL1			−0.4024	0.0203
ACSL3			−0.5575	0.0008
ACSL4			−0.6795	<0.0001
ACSL5			−0.5348	0.0013
ACSL6			0.5641	0.0006
ACSM4			0.5674	0.0006
ACSM5			−0.4469	0.0091
ACOT1	Acyl-CoA thioesterases	Regulate FFA oxidation in mitochondria and peroxisomes	−0.4368	0.011
ACOT12			0.3907	0.0246
ACOT6			0.4225	0.0143
ACOT7			−0.735	<0.0001
ACOT8			−0.6153	<0.0001
ACOT9			−0.7035	<0.0001
ACOX1	Acyl-CoA oxidases	The first enzyme of the fatty acid beta-oxidation pathway	−0.5194	0.002
ACOX2		Involved in the degradation of long branched fatty acids	−0.515	0.0022
ACOX3		Involved in the desaturation of 2-methyl-branched fatty acids in peroxisomes	−0.6116	0.0002
ACAT1	Acetyl-CoA transferases	Catalyses the last step of the mitochondrial beta-oxidation pathway	−0.497	0.0033
ACAA1		Involved in the beta-oxidation system of the peroxisomes	−0.6186	0.0001
ACAA2		Catalyses the last step of the mitochondrial fatty acid beta-oxidation	−0.5374	0.0013
ACAT2		Intracellular cholesterol esterification	−0.736	<0.0001
CPT1A	Fatty acid transport	Transport FFA into mitochondria for oxidation	−0.6013	0.0002
CPT1B			−0.5074	0.0026
CPT1C			−0.4131	0.0169
CPT2			−0.6003	0.0002
CRAT			−0.5916	0.0003
CROT			−0.5729	0.0005
FABP1		Facilitate FFA transport across membranes	0.538	0.0012
SLC27A1			−0.6785	<0.0001
SLC27A3			−0.7035	<0.0001
SLC27A4			−0.478	0.0003
SLC27A5			−0.4923	0.0036
FABP7		Cytoplasmatic FFA transport proteins	0.5572	0.0008
FABP2			0.5104	0.0024
FABP4			−0.5084	0.0025
FABP12			0.6093	0.0002
FABP5			−0.4686	0.006
PRKAA2	Fatty acid biosynthesis regulation	AMP-activated, alpha 2 catalytic subunit: inhibits ATP-consuming biosynthetic pathways	−0.6355	<0.0001
PRKAB1		Regulatory B1 subunit of AMP-activated protein kinase: inhibits ATP-consuming biosynthetic pathways	−0.8456	<0.0001
PRKAB2		Regulatory B2 subunit of AMP-activated protein kinase: inhibits ATP-consuming biosynthetic pathways	−0.7574	<0.0001
PRKACA		Catalytic subunits of protein kinase A: promotes fat utilization	0.6537	<0.0001
PRKACB		Catalytic subunit of cAMP (cyclic AMP)-dependent protein kinase	−0.5525	0.0009
PRKAG1		Regulatory G1 subunit of AMP-activated protein kinase: inhibits ATP-consuming biosynthetic pathways	−0.734	<0.0001
PRKAG2		Regulatory G2 subunit of AMP-activated protein kinase: inhibits ATP-consuming biosynthetic pathways	−0.4559	0.0077
ALDH2	Other fatty acid metabolism genes	Oxidizes aldehydes to generate carboxylic acids for use	−0.4078	0.0185
DECR1		Accessory enzymes that participate in the beta-oxidation and metabolism of unsaturated fatty enoyl-CoA esters	−0.5792	0.0004
ECHS1		Involved in mitochondrial fatty acid beta-oxidation pathway	−0.5137	0.0022
ECI2		Mitochondrial enzyme involved in beta-oxidation of unsaturated fatty acids	−0.6487	<0.0001
HADHA		Catalyses the last three steps of mitochondrial beta-oxidation of long chain fatty acids	−0.4682	0.006
MCEE		Involved in the degradation of odd chain-length fatty acids	−0.5745	0.0005
MUT		Involved in the degradation of odd chain-length fatty acids	−0.5805	0.0004
PPA1		Catalyses the hydrolysis of pyrophosphate to inorganic phosphate	−0.5451	0.001
GK	Triacylglycerol metabolism	Esterification of FFA with reduced FFA efflux	−0.6344	<0.0001
LIPE		In adipose tissue hydrolyses stored triglycerides to free fatty acids	−0.4335	0.0117
GK2		Key enzyme in the regulation of glycerol uptake and metabolism	0.5577	0.0007
GPD1		Synthesis of triglycerides	−0.5872	0.0003
GPD2		Synthesis of triglycerides	−0.3556	0.0423
BDH2	Ketogenesis and ketone body metabolism	Involved in the synthesis and degradation of ketone bodies	−0.5254	0.0017
HMGCS1		Involved in the synthesis and degradation of ketone bodies	−0.7764	<0.0001
OXCT2		Involved in ketone body catabolism.	0.3795	0.0294
HMGCL		Catalyzes the final step of leucine degradation and plays a key role in ketone body formation.	−0.6511	<0.0001

Glucose-dependent insulinotropic peptide receptor (GIPR)
a) Fatty acid metabolism genes and glucose-dependent insulinotropic peptide receptor (GIPR)
Genes	Family group	Function	Correlation coefficient	P value
ACAD11	Acetyl-CoA dehydrogenases	Promote FFA oxidation	−0.7507	<0.0001
ACADS			−0.5371	0.0013
ACADVL			−0.5531	0.0008
ACADM			−0.5551	0.0008
ACAD9			−0.5899	0.0003
ACSBG1	Acyl-CoA synthetases	Activate long- and medium-chain FFA for oxidation	−0.3797	0.0293
ACSBG2			0.6129	0.0001
ACSL1			−0.4024	0.0203
ACSL3			−0.5575	0.0008
ACSL4			−0.6795	<0.0001
ACSL5			−0.5348	0.0013
ACSL6			0.5641	0.0006
ACSM4			0.5674	0.0006
ACSM5			−0.4469	0.0091
ACOT1	Acyl-CoA thioesterases	Regulate FFA oxidation in mitochondria and peroxisomes	−0.4368	0.011
ACOT12			0.3907	0.0246
ACOT6			0.4225	0.0143
ACOT7			−0.735	<0.0001
ACOT8			−0.6153	<0.0001
ACOT9			−0.7035	<0.0001
ACOX1	Acyl-CoA oxidases	The first enzyme of the fatty acid beta-oxidation pathway	−0.5194	0.002
ACOX2		Involved in the degradation of long branched fatty acids	−0.515	0.0022
ACOX3		Involved in the desaturation of 2-methyl-branched fatty acids in peroxisomes	−0.6116	0.0002
ACAT1	Acetyl-CoA transferases	Catalyses the last step of the mitochondrial beta-oxidation pathway	−0.497	0.0033
ACAA1		Involved in the beta-oxidation system of the peroxisomes	−0.6186	0.0001
ACAA2		Catalyses the last step of the mitochondrial fatty acid beta-oxidation	−0.5374	0.0013
ACAT2		Intracellular cholesterol esterification	−0.736	<0.0001
CPT1A	Fatty acid transport	Transport FFA into mitochondria for oxidation	−0.6013	0.0002
CPT1B			−0.5074	0.0026
CPT1C			−0.4131	0.0169
CPT2			−0.6003	0.0002
CRAT			−0.5916	0.0003
CROT			−0.5729	0.0005
FABP1		Facilitate FFA transport across membranes	0.538	0.0012
SLC27A1			−0.6785	<0.0001
SLC27A3			−0.7035	<0.0001
SLC27A4			−0.478	0.0003
SLC27A5			−0.4923	0.0036
FABP7		Cytoplasmatic FFA transport proteins	0.5572	0.0008
FABP2			0.5104	0.0024
FABP4			−0.5084	0.0025
FABP12			0.6093	0.0002
FABP5			−0.4686	0.006
PRKAA2	Fatty acid biosynthesis regulation	AMP-activated, alpha 2 catalytic subunit: inhibits ATP-consuming biosynthetic pathways	−0.6355	<0.0001
PRKAB1		Regulatory B1 subunit of AMP-activated protein kinase: inhibits ATP-consuming biosynthetic pathways	−0.8456	<0.0001
PRKAB2		Regulatory B2 subunit of AMP-activated protein kinase: inhibits ATP-consuming biosynthetic pathways	−0.7574	<0.0001
PRKACA		Catalytic subunits of protein kinase A: promotes fat utilization	0.6537	<0.0001
PRKACB		Catalytic subunit of cAMP (cyclic AMP)-dependent protein kinase	−0.5525	0.0009
PRKAG1		Regulatory G1 subunit of AMP-activated protein kinase: inhibits ATP-consuming biosynthetic pathways	−0.734	<0.0001
PRKAG2		Regulatory G2 subunit of AMP-activated protein kinase: inhibits ATP-consuming biosynthetic pathways	−0.4559	0.0077
ALDH2	Other fatty acid metabolism genes	Oxidizes aldehydes to generate carboxylic acids for use	−0.4078	0.0185
DECR1		Accessory enzymes that participate in the beta-oxidation and metabolism of unsaturated fatty enoyl-CoA esters	−0.5792	0.0004
ECHS1		Involved in mitochondrial fatty acid beta-oxidation pathway	−0.5137	0.0022
ECI2		Mitochondrial enzyme involved in beta-oxidation of unsaturated fatty acids	−0.6487	<0.0001
HADHA		Catalyses the last three steps of mitochondrial beta-oxidation of long chain fatty acids	−0.4682	0.006
MCEE		Involved in the degradation of odd chain-length fatty acids	−0.5745	0.0005
MUT		Involved in the degradation of odd chain-length fatty acids	−0.5805	0.0004
PPA1		Catalyses the hydrolysis of pyrophosphate to inorganic phosphate	−0.5451	0.001
GK	Triacylglycerol metabolism	Esterification of FFA with reduced FFA efflux	−0.6344	<0.0001
LIPE		In adipose tissue hydrolyses stored triglycerides to free fatty acids	−0.4335	0.0117
GK2		Key enzyme in the regulation of glycerol uptake and metabolism	0.5577	0.0007
GPD1		Synthesis of triglycerides	−0.5872	0.0003
GPD2		Synthesis of triglycerides	−0.3556	0.0423
BDH2	Ketogenesis and ketone body metabolism	Involved in the synthesis and degradation of ketone bodies	−0.5254	0.0017
HMGCS1		Involved in the synthesis and degradation of ketone bodies	−0.7764	<0.0001
OXCT2		Involved in ketone body catabolism.	0.3795	0.0294
HMGCL		Catalyzes the final step of leucine degradation and plays a key role in ketone body formation.	−0.6511	<0.0001

b) Adipogenis genes and glucose-dependent insulinotropic peptide receptor (GIPR)
Genes	Family group	Function	Correlation coefficient	P value
ADIPOQ	Adipokines and hormones	Involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic, and anti-inflammatory activities	−0.548	0.001
ANGPT2		An inducer of fat uptake in adipose tissue for prevention of ectopic lipid deposition	−0.538	0.001
RETN		A feedback regulator of adipogenesis	0.438	0.011
AGT		Encodes for angiotensinogen precursor angiotensin	−0.540	0.001
ADIG		Adipocyte-specific protein that plays a role in adipocyte differentiation	0.569	0.001
FASN	PPARγ TARGETS	Fatty acid synthetase that catalyses the de novo biosynthesis of long-chain saturated fatty acids	−0.368	0.035
LIPE		In adipose tissue hydrolyses stored triglycerides to free fatty acids	−0.434	0.012
FABP4		Lipid transport protein in adipocytes	−0.508	0.003
ADRB2	Anti-adipogenesis	Beta-2-adrenergic receptor with lipolytic activity	−0.482	0.005
CDKN1A		A cyclin-dependent kinase inhibitor	−0.510	0.002
CDKN1B		A cyclin-dependent kinase inhibitor	−0.678	<0.0001
DDIT3		A member of the CCAAT/enhancer-binding protein (C/EBP) family of transcription factors that block adipogenesis	−0.731	<0.0001
FOXO1		Transcription factor that inhibits lipogenesis	−0.483	0.004
HES1		Transcription factor that inhibits lipogenesis	−0.670	<0.0001
LRP5		A transmembrane low-density lipoprotein receptor that binds and internalizes ligands in the process of receptor-mediated endocytosis	−0.492	0.004
NCOR2		Inhibits adipogenic differentiation by binding to PPARγ and represses the expression of PPARγ target genes	−0.743	<0.0001
SHH		Inhibits adipocyte differentiation	0.565	0.001
RUNX1T1		Recruits a range of co-repressors to acts as a negative regulator of adipogenesis	−0.636	<0.0001
SIRT1		Attenuate adipogenesis through PPARγ repressive acetylation	−0.778	<0.0001
SIRT2		Attenuate adipogenesis through PPARγ repressive acetylation	−0.626	<0.0001
TAZ		A transcriptional co-repressor of PPARγ that attenuates adipogenesis	−0.738	<0.0001
WNT3A		Inhibitor of adipogenesis	0.497	0.003
VDR		Unliganded VDR can activate adipogenesis through increased lipid accumulation	−0.532	0.001
TCF7L2		Adipose specific knockout of Tcf7l2 leads to adipocyte hypertrophy and impaired lipolysis	−0.397	0.022
TSC22D3		Inhibitor of the adipogenic master regulator PPARγ	−0.657	<0.0001
NCOA2	Anti-BAT tissue	Required with NCOA1 to control energy balance between white and brown adipose tissues	−0.704	<0.0001
TWIST1		Inhibit UCP-1 in brown adipocytes	−0.385	0.027
RB1		Molecular switch determining white vs. brown adipogenesis	−0.703	<0.0001
NR0B2		A negative regulator of PGC-1α expression in brown adipocytes	0.537	0.001
GATA2	Anti-white adipose tissue	Suppressor of adipocyte differentiation	−0.558	0.001
KLF2		Negative regulator of adipogenesis	−0.568	0.001
KLF3		Induction of Wnt10b and KLF3 decrease PPARγ expression	−0.567	0.001
AXIN1	Pro-adipogenesis	Promoter of adipocyte differentiation	−0.799	<0.0001
CCND1			−0.458	0.007
CDK4			−0.817	<0.0001
CEBPA			−0.579	0.0001
CEBPB			−0.553	0.001
CEBPD			−0.369	0.034
E2F1			−0.515	0.002
FGF1			−0.450	0.009
FGF2			−0.670	<0.0001
IRS2			0.560	0.001
SFRP1			−0.354	0.043
SLC2A4			−0.369	0.034
LMNA			−0.810	<0.0001
PPARG			−0.506	0.003
RXRA		Implicated in the development of dysfunctional white adipose tissue	−0.700	<0.0001
CREB1	Pro-brown adipose tissue	Involved in the transcriptional regulation of brown adipogenesis	−0.693	<0.0001
DIO2		Involved in the transcriptional regulation of brown adipogenesis	−0.791	<0.0001
INSR		Regulates metabolism in brown adipose tissue	−0.411	0.017
IRS1		Involved in the differentiation of brown adipocytes	−0.449	0.009
NRF1		Involved in brown adipose tissue thermogenic adaptation	−0.775	<0.0001
MAPK14		Controls brown adipocyte differentiation	−0.715	<0.0001
PPARA		Regulators of brown adipogenesis/metabolism	−0.619	0.0001
PPARD			−0.740	<0.0001
PPARGC1B			−0.389	0.025
PRDM16			−0.525	0.002
WNT5A			−0.458	0.007
SRC		Controls brown fat thermogenesis	−0.412	0.017
SIRT3		Controls brown fat thermogenesis	−0.745	<0.0001
BMP7	Pro-white adipose tissue	Promoters of white adipogenesis	−0.521	0.002
BMP2			−0.512	0.002
BMP4			−0.709	<0.0001
CEBPA		Required for differentiation of white adipocytes	−0.579	0.0004

b) Adipogenis genes and glucose-dependent insulinotropic peptide receptor (GIPR)
Genes	Family group	Function	Correlation coefficient	P value
ADIPOQ	Adipokines and hormones	Involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic, and anti-inflammatory activities	−0.548	0.001
ANGPT2		An inducer of fat uptake in adipose tissue for prevention of ectopic lipid deposition	−0.538	0.001
RETN		A feedback regulator of adipogenesis	0.438	0.011
AGT		Encodes for angiotensinogen precursor angiotensin	−0.540	0.001
ADIG		Adipocyte-specific protein that plays a role in adipocyte differentiation	0.569	0.001
FASN	PPARγ TARGETS	Fatty acid synthetase that catalyses the de novo biosynthesis of long-chain saturated fatty acids	−0.368	0.035
LIPE		In adipose tissue hydrolyses stored triglycerides to free fatty acids	−0.434	0.012
FABP4		Lipid transport protein in adipocytes	−0.508	0.003
ADRB2	Anti-adipogenesis	Beta-2-adrenergic receptor with lipolytic activity	−0.482	0.005
CDKN1A		A cyclin-dependent kinase inhibitor	−0.510	0.002
CDKN1B		A cyclin-dependent kinase inhibitor	−0.678	<0.0001
DDIT3		A member of the CCAAT/enhancer-binding protein (C/EBP) family of transcription factors that block adipogenesis	−0.731	<0.0001
FOXO1		Transcription factor that inhibits lipogenesis	−0.483	0.004
HES1		Transcription factor that inhibits lipogenesis	−0.670	<0.0001
LRP5		A transmembrane low-density lipoprotein receptor that binds and internalizes ligands in the process of receptor-mediated endocytosis	−0.492	0.004
NCOR2		Inhibits adipogenic differentiation by binding to PPARγ and represses the expression of PPARγ target genes	−0.743	<0.0001
SHH		Inhibits adipocyte differentiation	0.565	0.001
RUNX1T1		Recruits a range of co-repressors to acts as a negative regulator of adipogenesis	−0.636	<0.0001
SIRT1		Attenuate adipogenesis through PPARγ repressive acetylation	−0.778	<0.0001
SIRT2		Attenuate adipogenesis through PPARγ repressive acetylation	−0.626	<0.0001
TAZ		A transcriptional co-repressor of PPARγ that attenuates adipogenesis	−0.738	<0.0001
WNT3A		Inhibitor of adipogenesis	0.497	0.003
VDR		Unliganded VDR can activate adipogenesis through increased lipid accumulation	−0.532	0.001
TCF7L2		Adipose specific knockout of Tcf7l2 leads to adipocyte hypertrophy and impaired lipolysis	−0.397	0.022
TSC22D3		Inhibitor of the adipogenic master regulator PPARγ	−0.657	<0.0001
NCOA2	Anti-BAT tissue	Required with NCOA1 to control energy balance between white and brown adipose tissues	−0.704	<0.0001
TWIST1		Inhibit UCP-1 in brown adipocytes	−0.385	0.027
RB1		Molecular switch determining white vs. brown adipogenesis	−0.703	<0.0001
NR0B2		A negative regulator of PGC-1α expression in brown adipocytes	0.537	0.001
GATA2	Anti-white adipose tissue	Suppressor of adipocyte differentiation	−0.558	0.001
KLF2		Negative regulator of adipogenesis	−0.568	0.001
KLF3		Induction of Wnt10b and KLF3 decrease PPARγ expression	−0.567	0.001
AXIN1	Pro-adipogenesis	Promoter of adipocyte differentiation	−0.799	<0.0001
CCND1			−0.458	0.007
CDK4			−0.817	<0.0001
CEBPA			−0.579	0.0001
CEBPB			−0.553	0.001
CEBPD			−0.369	0.034
E2F1			−0.515	0.002
FGF1			−0.450	0.009
FGF2			−0.670	<0.0001
IRS2			0.560	0.001
SFRP1			−0.354	0.043
SLC2A4			−0.369	0.034
LMNA			−0.810	<0.0001
PPARG			−0.506	0.003
RXRA		Implicated in the development of dysfunctional white adipose tissue	−0.700	<0.0001
CREB1	Pro-brown adipose tissue	Involved in the transcriptional regulation of brown adipogenesis	−0.693	<0.0001
DIO2		Involved in the transcriptional regulation of brown adipogenesis	−0.791	<0.0001
INSR		Regulates metabolism in brown adipose tissue	−0.411	0.017
IRS1		Involved in the differentiation of brown adipocytes	−0.449	0.009
NRF1		Involved in brown adipose tissue thermogenic adaptation	−0.775	<0.0001
MAPK14		Controls brown adipocyte differentiation	−0.715	<0.0001
PPARA		Regulators of brown adipogenesis/metabolism	−0.619	0.0001
PPARD			−0.740	<0.0001
PPARGC1B			−0.389	0.025
PRDM16			−0.525	0.002
WNT5A			−0.458	0.007
SRC		Controls brown fat thermogenesis	−0.412	0.017
SIRT3		Controls brown fat thermogenesis	−0.745	<0.0001
BMP7	Pro-white adipose tissue	Promoters of white adipogenesis	−0.521	0.002
BMP2			−0.512	0.002
BMP4			−0.709	<0.0001
CEBPA		Required for differentiation of white adipocytes	−0.579	0.0004

Glucagon receptor (GCGR)
c) Fatty acid metabolism genes and glucagon receptor (GCGR)
Genes	Family group	Function	Correlation coefficient	P value
ACADSB	Acyl-CoA dehydrohgenases	It has the greatest activity towards the short branched chain acyl-CoA derivative	0.3753	0.0314
EHHADH		One of the four enzymes of the peroxisomal beta-oxidation pathway	−0.3693	0.0344
ACADL		One of the four enzymes that catalyse the initial step of mitochondrial beta-oxidation of straight-chain fatty acid	0.3815	0.0285
ACAD10		Involved in the beta-oxidation of fatty acids in mitochondria	0.4278	0.00130
ACSBG1	Acyl-CoA synthetases	Activate long- and medium-chain FFA for oxidation	0.3850	0.0269
ACSBG2			0.8244	<0.0001
ACSL6			0.3643	0.0371
ACSM3			0.7245	<0.0001
ACSM4			0.8426	<0.0001
ACOT12	Acyl-CoA thioesterases	Regulate FFA oxidation in mitochondria and peroxisomes	0.8235	<0.0001
ACOT6	Acyl-CoA thioesterases	Regulate FFA oxidation in mitochondria and peroxisomes	0.8001	<0.0001
CROT	Fatty acid transport	Transport FFA into mitochondria for oxidation	−0.4649	0.0064
SLC27A3		Facilitate FFA transport across membranes	0.6557	<0.0001
FABP1		Cytoplasmatic FFA transport proteins	0.7942	<0.0001
FABP2			0.8285	<0.0001
FABP12			0.7868	<0.0001
FABP6			0.7830	<0.0001
PRKAA1	Fatty acid biosynthesis regulation	AMP-activated, alpha 2 catalytic subunit: inhibits ATP-consuming biosynthetic pathways	0.5241	0.0017
PRKAA2		AMP-activated, alpha 1 catalytic subunit: inhibits ATP-consuming biosynthetic pathways	0.6581	<0.0001
PRKACA		Catalytic subunits of protein kinase A: promotes fat utilization	0.8138	<0.0001
PRKACB		Catalytic subunit of cAMP (cyclic AMP)-dependent protein kinase	0.5291	0.0015
PRKAG3		Regulatory G1 subunit of AMP-activated protein kinase: inhibits ATP-consuming biosynthetic pathways	0.4442	0.0096
PRKAG2		Regulatory G2 subunit of AMP-activated protein kinase: inhibits ATP-consuming biosynthetic pathways	0.9809	<0.0287
GK	Triacylglycerol metabolism	Esterification of FFA with reduced FFA efflux	−0.5013	0.0030
HMGCS2	Ketogenesis and ketone body metabolism	Involved in the synthesis and degradation of ketone bodies	0.8085	<0.0001
OXCT2	Ketogenesis and ketone body metabolism	Involeved in ketone body catabolism	0.7908	<0.0001

Glucagon receptor (GCGR)
c) Fatty acid metabolism genes and glucagon receptor (GCGR)
Genes	Family group	Function	Correlation coefficient	P value
ACADSB	Acyl-CoA dehydrohgenases	It has the greatest activity towards the short branched chain acyl-CoA derivative	0.3753	0.0314
EHHADH		One of the four enzymes of the peroxisomal beta-oxidation pathway	−0.3693	0.0344
ACADL		One of the four enzymes that catalyse the initial step of mitochondrial beta-oxidation of straight-chain fatty acid	0.3815	0.0285
ACAD10		Involved in the beta-oxidation of fatty acids in mitochondria	0.4278	0.00130
ACSBG1	Acyl-CoA synthetases	Activate long- and medium-chain FFA for oxidation	0.3850	0.0269
ACSBG2			0.8244	<0.0001
ACSL6			0.3643	0.0371
ACSM3			0.7245	<0.0001
ACSM4			0.8426	<0.0001
ACOT12	Acyl-CoA thioesterases	Regulate FFA oxidation in mitochondria and peroxisomes	0.8235	<0.0001
ACOT6	Acyl-CoA thioesterases	Regulate FFA oxidation in mitochondria and peroxisomes	0.8001	<0.0001
CROT	Fatty acid transport	Transport FFA into mitochondria for oxidation	−0.4649	0.0064
SLC27A3		Facilitate FFA transport across membranes	0.6557	<0.0001
FABP1		Cytoplasmatic FFA transport proteins	0.7942	<0.0001
FABP2			0.8285	<0.0001
FABP12			0.7868	<0.0001
FABP6			0.7830	<0.0001
PRKAA1	Fatty acid biosynthesis regulation	AMP-activated, alpha 2 catalytic subunit: inhibits ATP-consuming biosynthetic pathways	0.5241	0.0017
PRKAA2		AMP-activated, alpha 1 catalytic subunit: inhibits ATP-consuming biosynthetic pathways	0.6581	<0.0001
PRKACA		Catalytic subunits of protein kinase A: promotes fat utilization	0.8138	<0.0001
PRKACB		Catalytic subunit of cAMP (cyclic AMP)-dependent protein kinase	0.5291	0.0015
PRKAG3		Regulatory G1 subunit of AMP-activated protein kinase: inhibits ATP-consuming biosynthetic pathways	0.4442	0.0096
PRKAG2		Regulatory G2 subunit of AMP-activated protein kinase: inhibits ATP-consuming biosynthetic pathways	0.9809	<0.0287
GK	Triacylglycerol metabolism	Esterification of FFA with reduced FFA efflux	−0.5013	0.0030
HMGCS2	Ketogenesis and ketone body metabolism	Involved in the synthesis and degradation of ketone bodies	0.8085	<0.0001
OXCT2	Ketogenesis and ketone body metabolism	Involeved in ketone body catabolism	0.7908	<0.0001

d) Adipogenesis genes and glucagon receptor (GCGR)
Genes	Family group	Function	Correlation coefficient	P value
RETN	Adipokines and hormones	A feedback regulator of adipogenesis	0.6892	<0.0001
ADIG	Adipokines and hormones	Adipocyte-specific protein that plays a role in adipocyte differentiation	0.8425	<0.0001
HES1	Anti-adipogenesis	Inhibits adipocyte differentiation	−0.4395	0.0105
DLK1			0.7219	<0.0001
SHH			0.8773	<0.0001
TCF7L2			0.6788	<0.0001
WNT1			0.8179	<0.0001
WNT3A			0.8289	<0.0001
RUNX1T1			−0.4275	0.0131
NCOA2	Anti-brown adipose tissue	Required with NCOA1 to control energy balance between white and brown adipose tissues	0.5221	0.0018
WNT10B		It blocks brown adipose tissue development and expression of UCP-1.	0.7189	<0.0001
RB1		Molecular switch determining white vs. brown adipogenesis	0.5211	0.0019
NR0B2		A negative regulator of PGC-1α expression in brown adipocytes	0.8780	<0.0001
GATA2	Anti-white adipose tissue	Suppressor of adipocyte differentiation	0.6982	<0.0001
GATA3		Involved in white browning	0.4522	0.0082
KLF2		Negative regulator of adipogenesis	0.4318	0.0121
KLF3		Induction of Wnt10b and KLF3 decrease PPARγ expression	0.6765	<0.0001
IRS2	Pro-adipogenesis	Promoter of adipocyte differentiation	0.6517	<0.0001
CEBPB			0.4369	0.0110
FGF1			0.3830	0.0278
SFRP5			0.6130	0.0001
WNT5B			0.3917	0.0242
CREB1	Pro-brown adipose tissue	Involved in the transcriptional regulation of brown adipogenesis	−0.4830	0.0044
FOXC2			0.8443	<0.0001
MAPK14			0.3981	0.0218
PPARA		Regulators of brown adipogenesis/metabolism	0.7383	<0.0001
PPARD			0.8281	<0.0001
PPARGC1A			0.6832	<0.0001
UCP-1			0.5635	0.0006
PRDM16			0.7189	<0.0001
SRC		Controls brown fat thermogenesis	0.4412	0.0102
BMP7	Pro-white adipose tissue	Promoters of white adipogenesis	0.5625	<0.0007
KLF15	Pro-white adipose tissue	Promoters of white adipogenesis	0.6768	<0.0001

d) Adipogenesis genes and glucagon receptor (GCGR)
Genes	Family group	Function	Correlation coefficient	P value
RETN	Adipokines and hormones	A feedback regulator of adipogenesis	0.6892	<0.0001
ADIG	Adipokines and hormones	Adipocyte-specific protein that plays a role in adipocyte differentiation	0.8425	<0.0001
HES1	Anti-adipogenesis	Inhibits adipocyte differentiation	−0.4395	0.0105
DLK1			0.7219	<0.0001
SHH			0.8773	<0.0001
TCF7L2			0.6788	<0.0001
WNT1			0.8179	<0.0001
WNT3A			0.8289	<0.0001
RUNX1T1			−0.4275	0.0131
NCOA2	Anti-brown adipose tissue	Required with NCOA1 to control energy balance between white and brown adipose tissues	0.5221	0.0018
WNT10B		It blocks brown adipose tissue development and expression of UCP-1.	0.7189	<0.0001
RB1		Molecular switch determining white vs. brown adipogenesis	0.5211	0.0019
NR0B2		A negative regulator of PGC-1α expression in brown adipocytes	0.8780	<0.0001
GATA2	Anti-white adipose tissue	Suppressor of adipocyte differentiation	0.6982	<0.0001
GATA3		Involved in white browning	0.4522	0.0082
KLF2		Negative regulator of adipogenesis	0.4318	0.0121
KLF3		Induction of Wnt10b and KLF3 decrease PPARγ expression	0.6765	<0.0001
IRS2	Pro-adipogenesis	Promoter of adipocyte differentiation	0.6517	<0.0001
CEBPB			0.4369	0.0110
FGF1			0.3830	0.0278
SFRP5			0.6130	0.0001
WNT5B			0.3917	0.0242
CREB1	Pro-brown adipose tissue	Involved in the transcriptional regulation of brown adipogenesis	−0.4830	0.0044
FOXC2			0.8443	<0.0001
MAPK14			0.3981	0.0218
PPARA		Regulators of brown adipogenesis/metabolism	0.7383	<0.0001
PPARD			0.8281	<0.0001
PPARGC1A			0.6832	<0.0001
UCP-1			0.5635	0.0006
PRDM16			0.7189	<0.0001
SRC		Controls brown fat thermogenesis	0.4412	0.0102
BMP7	Pro-white adipose tissue	Promoters of white adipogenesis	0.5625	<0.0007
KLF15	Pro-white adipose tissue	Promoters of white adipogenesis	0.6768	<0.0001

Table reports existing positive and negative correlations of glucose-dependent insulinotropic peptide receptor (GIPR) and glucagon receptor (GCGR) with genes involved in fatty acid metabolism and adipogenesis.

Spearman correlation coefficients and corresponding P value are reported.

Table 2

Open in new tab

Correlation analysis of EAT GIPR and EAT GCGR with genes involved in FFA metabolism and adipogenesis

Glucose-dependent insulinotropic peptide receptor (GIPR)
a) Fatty acid metabolism genes and glucose-dependent insulinotropic peptide receptor (GIPR)
Genes	Family group	Function	Correlation coefficient	P value
ACAD11	Acetyl-CoA dehydrogenases	Promote FFA oxidation	−0.7507	<0.0001
ACADS			−0.5371	0.0013
ACADVL			−0.5531	0.0008
ACADM			−0.5551	0.0008
ACAD9			−0.5899	0.0003
ACSBG1	Acyl-CoA synthetases	Activate long- and medium-chain FFA for oxidation	−0.3797	0.0293
ACSBG2			0.6129	0.0001
ACSL1			−0.4024	0.0203
ACSL3			−0.5575	0.0008
ACSL4			−0.6795	<0.0001
ACSL5			−0.5348	0.0013
ACSL6			0.5641	0.0006
ACSM4			0.5674	0.0006
ACSM5			−0.4469	0.0091
ACOT1	Acyl-CoA thioesterases	Regulate FFA oxidation in mitochondria and peroxisomes	−0.4368	0.011
ACOT12			0.3907	0.0246
ACOT6			0.4225	0.0143
ACOT7			−0.735	<0.0001
ACOT8			−0.6153	<0.0001
ACOT9			−0.7035	<0.0001
ACOX1	Acyl-CoA oxidases	The first enzyme of the fatty acid beta-oxidation pathway	−0.5194	0.002
ACOX2		Involved in the degradation of long branched fatty acids	−0.515	0.0022
ACOX3		Involved in the desaturation of 2-methyl-branched fatty acids in peroxisomes	−0.6116	0.0002
ACAT1	Acetyl-CoA transferases	Catalyses the last step of the mitochondrial beta-oxidation pathway	−0.497	0.0033
ACAA1		Involved in the beta-oxidation system of the peroxisomes	−0.6186	0.0001
ACAA2		Catalyses the last step of the mitochondrial fatty acid beta-oxidation	−0.5374	0.0013
ACAT2		Intracellular cholesterol esterification	−0.736	<0.0001
CPT1A	Fatty acid transport	Transport FFA into mitochondria for oxidation	−0.6013	0.0002
CPT1B			−0.5074	0.0026
CPT1C			−0.4131	0.0169
CPT2			−0.6003	0.0002
CRAT			−0.5916	0.0003
CROT			−0.5729	0.0005
FABP1		Facilitate FFA transport across membranes	0.538	0.0012
SLC27A1			−0.6785	<0.0001
SLC27A3			−0.7035	<0.0001
SLC27A4			−0.478	0.0003
SLC27A5			−0.4923	0.0036
FABP7		Cytoplasmatic FFA transport proteins	0.5572	0.0008
FABP2			0.5104	0.0024
FABP4			−0.5084	0.0025
FABP12			0.6093	0.0002
FABP5			−0.4686	0.006
PRKAA2	Fatty acid biosynthesis regulation	AMP-activated, alpha 2 catalytic subunit: inhibits ATP-consuming biosynthetic pathways	−0.6355	<0.0001
PRKAB1		Regulatory B1 subunit of AMP-activated protein kinase: inhibits ATP-consuming biosynthetic pathways	−0.8456	<0.0001
PRKAB2		Regulatory B2 subunit of AMP-activated protein kinase: inhibits ATP-consuming biosynthetic pathways	−0.7574	<0.0001
PRKACA		Catalytic subunits of protein kinase A: promotes fat utilization	0.6537	<0.0001
PRKACB		Catalytic subunit of cAMP (cyclic AMP)-dependent protein kinase	−0.5525	0.0009
PRKAG1		Regulatory G1 subunit of AMP-activated protein kinase: inhibits ATP-consuming biosynthetic pathways	−0.734	<0.0001
PRKAG2		Regulatory G2 subunit of AMP-activated protein kinase: inhibits ATP-consuming biosynthetic pathways	−0.4559	0.0077
ALDH2	Other fatty acid metabolism genes	Oxidizes aldehydes to generate carboxylic acids for use	−0.4078	0.0185
DECR1		Accessory enzymes that participate in the beta-oxidation and metabolism of unsaturated fatty enoyl-CoA esters	−0.5792	0.0004
ECHS1		Involved in mitochondrial fatty acid beta-oxidation pathway	−0.5137	0.0022
ECI2		Mitochondrial enzyme involved in beta-oxidation of unsaturated fatty acids	−0.6487	<0.0001
HADHA		Catalyses the last three steps of mitochondrial beta-oxidation of long chain fatty acids	−0.4682	0.006
MCEE		Involved in the degradation of odd chain-length fatty acids	−0.5745	0.0005
MUT		Involved in the degradation of odd chain-length fatty acids	−0.5805	0.0004
PPA1		Catalyses the hydrolysis of pyrophosphate to inorganic phosphate	−0.5451	0.001
GK	Triacylglycerol metabolism	Esterification of FFA with reduced FFA efflux	−0.6344	<0.0001
LIPE		In adipose tissue hydrolyses stored triglycerides to free fatty acids	−0.4335	0.0117
GK2		Key enzyme in the regulation of glycerol uptake and metabolism	0.5577	0.0007
GPD1		Synthesis of triglycerides	−0.5872	0.0003
GPD2		Synthesis of triglycerides	−0.3556	0.0423
BDH2	Ketogenesis and ketone body metabolism	Involved in the synthesis and degradation of ketone bodies	−0.5254	0.0017
HMGCS1		Involved in the synthesis and degradation of ketone bodies	−0.7764	<0.0001
OXCT2		Involved in ketone body catabolism.	0.3795	0.0294
HMGCL		Catalyzes the final step of leucine degradation and plays a key role in ketone body formation.	−0.6511	<0.0001

Glucose-dependent insulinotropic peptide receptor (GIPR)
a) Fatty acid metabolism genes and glucose-dependent insulinotropic peptide receptor (GIPR)
Genes	Family group	Function	Correlation coefficient	P value
ACAD11	Acetyl-CoA dehydrogenases	Promote FFA oxidation	−0.7507	<0.0001
ACADS			−0.5371	0.0013
ACADVL			−0.5531	0.0008
ACADM			−0.5551	0.0008
ACAD9			−0.5899	0.0003
ACSBG1	Acyl-CoA synthetases	Activate long- and medium-chain FFA for oxidation	−0.3797	0.0293
ACSBG2			0.6129	0.0001
ACSL1			−0.4024	0.0203
ACSL3			−0.5575	0.0008
ACSL4			−0.6795	<0.0001
ACSL5			−0.5348	0.0013
ACSL6			0.5641	0.0006
ACSM4			0.5674	0.0006
ACSM5			−0.4469	0.0091
ACOT1	Acyl-CoA thioesterases	Regulate FFA oxidation in mitochondria and peroxisomes	−0.4368	0.011
ACOT12			0.3907	0.0246
ACOT6			0.4225	0.0143
ACOT7			−0.735	<0.0001
ACOT8			−0.6153	<0.0001
ACOT9			−0.7035	<0.0001
ACOX1	Acyl-CoA oxidases	The first enzyme of the fatty acid beta-oxidation pathway	−0.5194	0.002
ACOX2		Involved in the degradation of long branched fatty acids	−0.515	0.0022
ACOX3		Involved in the desaturation of 2-methyl-branched fatty acids in peroxisomes	−0.6116	0.0002
ACAT1	Acetyl-CoA transferases	Catalyses the last step of the mitochondrial beta-oxidation pathway	−0.497	0.0033
ACAA1		Involved in the beta-oxidation system of the peroxisomes	−0.6186	0.0001
ACAA2		Catalyses the last step of the mitochondrial fatty acid beta-oxidation	−0.5374	0.0013
ACAT2		Intracellular cholesterol esterification	−0.736	<0.0001
CPT1A	Fatty acid transport	Transport FFA into mitochondria for oxidation	−0.6013	0.0002
CPT1B			−0.5074	0.0026
CPT1C			−0.4131	0.0169
CPT2			−0.6003	0.0002
CRAT			−0.5916	0.0003
CROT			−0.5729	0.0005
FABP1		Facilitate FFA transport across membranes	0.538	0.0012
SLC27A1			−0.6785	<0.0001
SLC27A3			−0.7035	<0.0001
SLC27A4			−0.478	0.0003
SLC27A5			−0.4923	0.0036
FABP7		Cytoplasmatic FFA transport proteins	0.5572	0.0008
FABP2			0.5104	0.0024
FABP4			−0.5084	0.0025
FABP12			0.6093	0.0002
FABP5			−0.4686	0.006
PRKAA2	Fatty acid biosynthesis regulation	AMP-activated, alpha 2 catalytic subunit: inhibits ATP-consuming biosynthetic pathways	−0.6355	<0.0001
PRKAB1		Regulatory B1 subunit of AMP-activated protein kinase: inhibits ATP-consuming biosynthetic pathways	−0.8456	<0.0001
PRKAB2		Regulatory B2 subunit of AMP-activated protein kinase: inhibits ATP-consuming biosynthetic pathways	−0.7574	<0.0001
PRKACA		Catalytic subunits of protein kinase A: promotes fat utilization	0.6537	<0.0001
PRKACB		Catalytic subunit of cAMP (cyclic AMP)-dependent protein kinase	−0.5525	0.0009
PRKAG1		Regulatory G1 subunit of AMP-activated protein kinase: inhibits ATP-consuming biosynthetic pathways	−0.734	<0.0001
PRKAG2		Regulatory G2 subunit of AMP-activated protein kinase: inhibits ATP-consuming biosynthetic pathways	−0.4559	0.0077
ALDH2	Other fatty acid metabolism genes	Oxidizes aldehydes to generate carboxylic acids for use	−0.4078	0.0185
DECR1		Accessory enzymes that participate in the beta-oxidation and metabolism of unsaturated fatty enoyl-CoA esters	−0.5792	0.0004
ECHS1		Involved in mitochondrial fatty acid beta-oxidation pathway	−0.5137	0.0022
ECI2		Mitochondrial enzyme involved in beta-oxidation of unsaturated fatty acids	−0.6487	<0.0001
HADHA		Catalyses the last three steps of mitochondrial beta-oxidation of long chain fatty acids	−0.4682	0.006
MCEE		Involved in the degradation of odd chain-length fatty acids	−0.5745	0.0005
MUT		Involved in the degradation of odd chain-length fatty acids	−0.5805	0.0004
PPA1		Catalyses the hydrolysis of pyrophosphate to inorganic phosphate	−0.5451	0.001
GK	Triacylglycerol metabolism	Esterification of FFA with reduced FFA efflux	−0.6344	<0.0001
LIPE		In adipose tissue hydrolyses stored triglycerides to free fatty acids	−0.4335	0.0117
GK2		Key enzyme in the regulation of glycerol uptake and metabolism	0.5577	0.0007
GPD1		Synthesis of triglycerides	−0.5872	0.0003
GPD2		Synthesis of triglycerides	−0.3556	0.0423
BDH2	Ketogenesis and ketone body metabolism	Involved in the synthesis and degradation of ketone bodies	−0.5254	0.0017
HMGCS1		Involved in the synthesis and degradation of ketone bodies	−0.7764	<0.0001
OXCT2		Involved in ketone body catabolism.	0.3795	0.0294
HMGCL		Catalyzes the final step of leucine degradation and plays a key role in ketone body formation.	−0.6511	<0.0001

b) Adipogenis genes and glucose-dependent insulinotropic peptide receptor (GIPR)
Genes	Family group	Function	Correlation coefficient	P value
ADIPOQ	Adipokines and hormones	Involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic, and anti-inflammatory activities	−0.548	0.001
ANGPT2		An inducer of fat uptake in adipose tissue for prevention of ectopic lipid deposition	−0.538	0.001
RETN		A feedback regulator of adipogenesis	0.438	0.011
AGT		Encodes for angiotensinogen precursor angiotensin	−0.540	0.001
ADIG		Adipocyte-specific protein that plays a role in adipocyte differentiation	0.569	0.001
FASN	PPARγ TARGETS	Fatty acid synthetase that catalyses the de novo biosynthesis of long-chain saturated fatty acids	−0.368	0.035
LIPE		In adipose tissue hydrolyses stored triglycerides to free fatty acids	−0.434	0.012
FABP4		Lipid transport protein in adipocytes	−0.508	0.003
ADRB2	Anti-adipogenesis	Beta-2-adrenergic receptor with lipolytic activity	−0.482	0.005
CDKN1A		A cyclin-dependent kinase inhibitor	−0.510	0.002
CDKN1B		A cyclin-dependent kinase inhibitor	−0.678	<0.0001
DDIT3		A member of the CCAAT/enhancer-binding protein (C/EBP) family of transcription factors that block adipogenesis	−0.731	<0.0001
FOXO1		Transcription factor that inhibits lipogenesis	−0.483	0.004
HES1		Transcription factor that inhibits lipogenesis	−0.670	<0.0001
LRP5		A transmembrane low-density lipoprotein receptor that binds and internalizes ligands in the process of receptor-mediated endocytosis	−0.492	0.004
NCOR2		Inhibits adipogenic differentiation by binding to PPARγ and represses the expression of PPARγ target genes	−0.743	<0.0001
SHH		Inhibits adipocyte differentiation	0.565	0.001
RUNX1T1		Recruits a range of co-repressors to acts as a negative regulator of adipogenesis	−0.636	<0.0001
SIRT1		Attenuate adipogenesis through PPARγ repressive acetylation	−0.778	<0.0001
SIRT2		Attenuate adipogenesis through PPARγ repressive acetylation	−0.626	<0.0001
TAZ		A transcriptional co-repressor of PPARγ that attenuates adipogenesis	−0.738	<0.0001
WNT3A		Inhibitor of adipogenesis	0.497	0.003
VDR		Unliganded VDR can activate adipogenesis through increased lipid accumulation	−0.532	0.001
TCF7L2		Adipose specific knockout of Tcf7l2 leads to adipocyte hypertrophy and impaired lipolysis	−0.397	0.022
TSC22D3		Inhibitor of the adipogenic master regulator PPARγ	−0.657	<0.0001
NCOA2	Anti-BAT tissue	Required with NCOA1 to control energy balance between white and brown adipose tissues	−0.704	<0.0001
TWIST1		Inhibit UCP-1 in brown adipocytes	−0.385	0.027
RB1		Molecular switch determining white vs. brown adipogenesis	−0.703	<0.0001
NR0B2		A negative regulator of PGC-1α expression in brown adipocytes	0.537	0.001
GATA2	Anti-white adipose tissue	Suppressor of adipocyte differentiation	−0.558	0.001
KLF2		Negative regulator of adipogenesis	−0.568	0.001
KLF3		Induction of Wnt10b and KLF3 decrease PPARγ expression	−0.567	0.001
AXIN1	Pro-adipogenesis	Promoter of adipocyte differentiation	−0.799	<0.0001
CCND1			−0.458	0.007
CDK4			−0.817	<0.0001
CEBPA			−0.579	0.0001
CEBPB			−0.553	0.001
CEBPD			−0.369	0.034
E2F1			−0.515	0.002
FGF1			−0.450	0.009
FGF2			−0.670	<0.0001
IRS2			0.560	0.001
SFRP1			−0.354	0.043
SLC2A4			−0.369	0.034
LMNA			−0.810	<0.0001
PPARG			−0.506	0.003
RXRA		Implicated in the development of dysfunctional white adipose tissue	−0.700	<0.0001
CREB1	Pro-brown adipose tissue	Involved in the transcriptional regulation of brown adipogenesis	−0.693	<0.0001
DIO2		Involved in the transcriptional regulation of brown adipogenesis	−0.791	<0.0001
INSR		Regulates metabolism in brown adipose tissue	−0.411	0.017
IRS1		Involved in the differentiation of brown adipocytes	−0.449	0.009
NRF1		Involved in brown adipose tissue thermogenic adaptation	−0.775	<0.0001
MAPK14		Controls brown adipocyte differentiation	−0.715	<0.0001
PPARA		Regulators of brown adipogenesis/metabolism	−0.619	0.0001
PPARD			−0.740	<0.0001
PPARGC1B			−0.389	0.025
PRDM16			−0.525	0.002
WNT5A			−0.458	0.007
SRC		Controls brown fat thermogenesis	−0.412	0.017
SIRT3		Controls brown fat thermogenesis	−0.745	<0.0001
BMP7	Pro-white adipose tissue	Promoters of white adipogenesis	−0.521	0.002
BMP2			−0.512	0.002
BMP4			−0.709	<0.0001
CEBPA		Required for differentiation of white adipocytes	−0.579	0.0004

b) Adipogenis genes and glucose-dependent insulinotropic peptide receptor (GIPR)
Genes	Family group	Function	Correlation coefficient	P value
ADIPOQ	Adipokines and hormones	Involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic, and anti-inflammatory activities	−0.548	0.001
ANGPT2		An inducer of fat uptake in adipose tissue for prevention of ectopic lipid deposition	−0.538	0.001
RETN		A feedback regulator of adipogenesis	0.438	0.011
AGT		Encodes for angiotensinogen precursor angiotensin	−0.540	0.001
ADIG		Adipocyte-specific protein that plays a role in adipocyte differentiation	0.569	0.001
FASN	PPARγ TARGETS	Fatty acid synthetase that catalyses the de novo biosynthesis of long-chain saturated fatty acids	−0.368	0.035
LIPE		In adipose tissue hydrolyses stored triglycerides to free fatty acids	−0.434	0.012
FABP4		Lipid transport protein in adipocytes	−0.508	0.003
ADRB2	Anti-adipogenesis	Beta-2-adrenergic receptor with lipolytic activity	−0.482	0.005
CDKN1A		A cyclin-dependent kinase inhibitor	−0.510	0.002
CDKN1B		A cyclin-dependent kinase inhibitor	−0.678	<0.0001
DDIT3		A member of the CCAAT/enhancer-binding protein (C/EBP) family of transcription factors that block adipogenesis	−0.731	<0.0001
FOXO1		Transcription factor that inhibits lipogenesis	−0.483	0.004
HES1		Transcription factor that inhibits lipogenesis	−0.670	<0.0001
LRP5		A transmembrane low-density lipoprotein receptor that binds and internalizes ligands in the process of receptor-mediated endocytosis	−0.492	0.004
NCOR2		Inhibits adipogenic differentiation by binding to PPARγ and represses the expression of PPARγ target genes	−0.743	<0.0001
SHH		Inhibits adipocyte differentiation	0.565	0.001
RUNX1T1		Recruits a range of co-repressors to acts as a negative regulator of adipogenesis	−0.636	<0.0001
SIRT1		Attenuate adipogenesis through PPARγ repressive acetylation	−0.778	<0.0001
SIRT2		Attenuate adipogenesis through PPARγ repressive acetylation	−0.626	<0.0001
TAZ		A transcriptional co-repressor of PPARγ that attenuates adipogenesis	−0.738	<0.0001
WNT3A		Inhibitor of adipogenesis	0.497	0.003
VDR		Unliganded VDR can activate adipogenesis through increased lipid accumulation	−0.532	0.001
TCF7L2		Adipose specific knockout of Tcf7l2 leads to adipocyte hypertrophy and impaired lipolysis	−0.397	0.022
TSC22D3		Inhibitor of the adipogenic master regulator PPARγ	−0.657	<0.0001
NCOA2	Anti-BAT tissue	Required with NCOA1 to control energy balance between white and brown adipose tissues	−0.704	<0.0001
TWIST1		Inhibit UCP-1 in brown adipocytes	−0.385	0.027
RB1		Molecular switch determining white vs. brown adipogenesis	−0.703	<0.0001
NR0B2		A negative regulator of PGC-1α expression in brown adipocytes	0.537	0.001
GATA2	Anti-white adipose tissue	Suppressor of adipocyte differentiation	−0.558	0.001
KLF2		Negative regulator of adipogenesis	−0.568	0.001
KLF3		Induction of Wnt10b and KLF3 decrease PPARγ expression	−0.567	0.001
AXIN1	Pro-adipogenesis	Promoter of adipocyte differentiation	−0.799	<0.0001
CCND1			−0.458	0.007
CDK4			−0.817	<0.0001
CEBPA			−0.579	0.0001
CEBPB			−0.553	0.001
CEBPD			−0.369	0.034
E2F1			−0.515	0.002
FGF1			−0.450	0.009
FGF2			−0.670	<0.0001
IRS2			0.560	0.001
SFRP1			−0.354	0.043
SLC2A4			−0.369	0.034
LMNA			−0.810	<0.0001
PPARG			−0.506	0.003
RXRA		Implicated in the development of dysfunctional white adipose tissue	−0.700	<0.0001
CREB1	Pro-brown adipose tissue	Involved in the transcriptional regulation of brown adipogenesis	−0.693	<0.0001
DIO2		Involved in the transcriptional regulation of brown adipogenesis	−0.791	<0.0001
INSR		Regulates metabolism in brown adipose tissue	−0.411	0.017
IRS1		Involved in the differentiation of brown adipocytes	−0.449	0.009
NRF1		Involved in brown adipose tissue thermogenic adaptation	−0.775	<0.0001
MAPK14		Controls brown adipocyte differentiation	−0.715	<0.0001
PPARA		Regulators of brown adipogenesis/metabolism	−0.619	0.0001
PPARD			−0.740	<0.0001
PPARGC1B			−0.389	0.025
PRDM16			−0.525	0.002
WNT5A			−0.458	0.007
SRC		Controls brown fat thermogenesis	−0.412	0.017
SIRT3		Controls brown fat thermogenesis	−0.745	<0.0001
BMP7	Pro-white adipose tissue	Promoters of white adipogenesis	−0.521	0.002
BMP2			−0.512	0.002
BMP4			−0.709	<0.0001
CEBPA		Required for differentiation of white adipocytes	−0.579	0.0004

Glucagon receptor (GCGR)
c) Fatty acid metabolism genes and glucagon receptor (GCGR)
Genes	Family group	Function	Correlation coefficient	P value
ACADSB	Acyl-CoA dehydrohgenases	It has the greatest activity towards the short branched chain acyl-CoA derivative	0.3753	0.0314
EHHADH		One of the four enzymes of the peroxisomal beta-oxidation pathway	−0.3693	0.0344
ACADL		One of the four enzymes that catalyse the initial step of mitochondrial beta-oxidation of straight-chain fatty acid	0.3815	0.0285
ACAD10		Involved in the beta-oxidation of fatty acids in mitochondria	0.4278	0.00130
ACSBG1	Acyl-CoA synthetases	Activate long- and medium-chain FFA for oxidation	0.3850	0.0269
ACSBG2			0.8244	<0.0001
ACSL6			0.3643	0.0371
ACSM3			0.7245	<0.0001
ACSM4			0.8426	<0.0001
ACOT12	Acyl-CoA thioesterases	Regulate FFA oxidation in mitochondria and peroxisomes	0.8235	<0.0001
ACOT6	Acyl-CoA thioesterases	Regulate FFA oxidation in mitochondria and peroxisomes	0.8001	<0.0001
CROT	Fatty acid transport	Transport FFA into mitochondria for oxidation	−0.4649	0.0064
SLC27A3		Facilitate FFA transport across membranes	0.6557	<0.0001
FABP1		Cytoplasmatic FFA transport proteins	0.7942	<0.0001
FABP2			0.8285	<0.0001
FABP12			0.7868	<0.0001
FABP6			0.7830	<0.0001
PRKAA1	Fatty acid biosynthesis regulation	AMP-activated, alpha 2 catalytic subunit: inhibits ATP-consuming biosynthetic pathways	0.5241	0.0017
PRKAA2		AMP-activated, alpha 1 catalytic subunit: inhibits ATP-consuming biosynthetic pathways	0.6581	<0.0001
PRKACA		Catalytic subunits of protein kinase A: promotes fat utilization	0.8138	<0.0001
PRKACB		Catalytic subunit of cAMP (cyclic AMP)-dependent protein kinase	0.5291	0.0015
PRKAG3		Regulatory G1 subunit of AMP-activated protein kinase: inhibits ATP-consuming biosynthetic pathways	0.4442	0.0096
PRKAG2		Regulatory G2 subunit of AMP-activated protein kinase: inhibits ATP-consuming biosynthetic pathways	0.9809	<0.0287
GK	Triacylglycerol metabolism	Esterification of FFA with reduced FFA efflux	−0.5013	0.0030
HMGCS2	Ketogenesis and ketone body metabolism	Involved in the synthesis and degradation of ketone bodies	0.8085	<0.0001
OXCT2	Ketogenesis and ketone body metabolism	Involeved in ketone body catabolism	0.7908	<0.0001

Glucagon receptor (GCGR)
c) Fatty acid metabolism genes and glucagon receptor (GCGR)
Genes	Family group	Function	Correlation coefficient	P value
ACADSB	Acyl-CoA dehydrohgenases	It has the greatest activity towards the short branched chain acyl-CoA derivative	0.3753	0.0314
EHHADH		One of the four enzymes of the peroxisomal beta-oxidation pathway	−0.3693	0.0344
ACADL		One of the four enzymes that catalyse the initial step of mitochondrial beta-oxidation of straight-chain fatty acid	0.3815	0.0285
ACAD10		Involved in the beta-oxidation of fatty acids in mitochondria	0.4278	0.00130
ACSBG1	Acyl-CoA synthetases	Activate long- and medium-chain FFA for oxidation	0.3850	0.0269
ACSBG2			0.8244	<0.0001
ACSL6			0.3643	0.0371
ACSM3			0.7245	<0.0001
ACSM4			0.8426	<0.0001
ACOT12	Acyl-CoA thioesterases	Regulate FFA oxidation in mitochondria and peroxisomes	0.8235	<0.0001
ACOT6	Acyl-CoA thioesterases	Regulate FFA oxidation in mitochondria and peroxisomes	0.8001	<0.0001
CROT	Fatty acid transport	Transport FFA into mitochondria for oxidation	−0.4649	0.0064
SLC27A3		Facilitate FFA transport across membranes	0.6557	<0.0001
FABP1		Cytoplasmatic FFA transport proteins	0.7942	<0.0001
FABP2			0.8285	<0.0001
FABP12			0.7868	<0.0001
FABP6			0.7830	<0.0001
PRKAA1	Fatty acid biosynthesis regulation	AMP-activated, alpha 2 catalytic subunit: inhibits ATP-consuming biosynthetic pathways	0.5241	0.0017
PRKAA2		AMP-activated, alpha 1 catalytic subunit: inhibits ATP-consuming biosynthetic pathways	0.6581	<0.0001
PRKACA		Catalytic subunits of protein kinase A: promotes fat utilization	0.8138	<0.0001
PRKACB		Catalytic subunit of cAMP (cyclic AMP)-dependent protein kinase	0.5291	0.0015
PRKAG3		Regulatory G1 subunit of AMP-activated protein kinase: inhibits ATP-consuming biosynthetic pathways	0.4442	0.0096
PRKAG2		Regulatory G2 subunit of AMP-activated protein kinase: inhibits ATP-consuming biosynthetic pathways	0.9809	<0.0287
GK	Triacylglycerol metabolism	Esterification of FFA with reduced FFA efflux	−0.5013	0.0030
HMGCS2	Ketogenesis and ketone body metabolism	Involved in the synthesis and degradation of ketone bodies	0.8085	<0.0001
OXCT2	Ketogenesis and ketone body metabolism	Involeved in ketone body catabolism	0.7908	<0.0001

d) Adipogenesis genes and glucagon receptor (GCGR)
Genes	Family group	Function	Correlation coefficient	P value
RETN	Adipokines and hormones	A feedback regulator of adipogenesis	0.6892	<0.0001
ADIG	Adipokines and hormones	Adipocyte-specific protein that plays a role in adipocyte differentiation	0.8425	<0.0001
HES1	Anti-adipogenesis	Inhibits adipocyte differentiation	−0.4395	0.0105
DLK1			0.7219	<0.0001
SHH			0.8773	<0.0001
TCF7L2			0.6788	<0.0001
WNT1			0.8179	<0.0001
WNT3A			0.8289	<0.0001
RUNX1T1			−0.4275	0.0131
NCOA2	Anti-brown adipose tissue	Required with NCOA1 to control energy balance between white and brown adipose tissues	0.5221	0.0018
WNT10B		It blocks brown adipose tissue development and expression of UCP-1.	0.7189	<0.0001
RB1		Molecular switch determining white vs. brown adipogenesis	0.5211	0.0019
NR0B2		A negative regulator of PGC-1α expression in brown adipocytes	0.8780	<0.0001
GATA2	Anti-white adipose tissue	Suppressor of adipocyte differentiation	0.6982	<0.0001
GATA3		Involved in white browning	0.4522	0.0082
KLF2		Negative regulator of adipogenesis	0.4318	0.0121
KLF3		Induction of Wnt10b and KLF3 decrease PPARγ expression	0.6765	<0.0001
IRS2	Pro-adipogenesis	Promoter of adipocyte differentiation	0.6517	<0.0001
CEBPB			0.4369	0.0110
FGF1			0.3830	0.0278
SFRP5			0.6130	0.0001
WNT5B			0.3917	0.0242
CREB1	Pro-brown adipose tissue	Involved in the transcriptional regulation of brown adipogenesis	−0.4830	0.0044
FOXC2			0.8443	<0.0001
MAPK14			0.3981	0.0218
PPARA		Regulators of brown adipogenesis/metabolism	0.7383	<0.0001
PPARD			0.8281	<0.0001
PPARGC1A			0.6832	<0.0001
UCP-1			0.5635	0.0006
PRDM16			0.7189	<0.0001
SRC		Controls brown fat thermogenesis	0.4412	0.0102
BMP7	Pro-white adipose tissue	Promoters of white adipogenesis	0.5625	<0.0007
KLF15	Pro-white adipose tissue	Promoters of white adipogenesis	0.6768	<0.0001

d) Adipogenesis genes and glucagon receptor (GCGR)
Genes	Family group	Function	Correlation coefficient	P value
RETN	Adipokines and hormones	A feedback regulator of adipogenesis	0.6892	<0.0001
ADIG	Adipokines and hormones	Adipocyte-specific protein that plays a role in adipocyte differentiation	0.8425	<0.0001
HES1	Anti-adipogenesis	Inhibits adipocyte differentiation	−0.4395	0.0105
DLK1			0.7219	<0.0001
SHH			0.8773	<0.0001
TCF7L2			0.6788	<0.0001
WNT1			0.8179	<0.0001
WNT3A			0.8289	<0.0001
RUNX1T1			−0.4275	0.0131
NCOA2	Anti-brown adipose tissue	Required with NCOA1 to control energy balance between white and brown adipose tissues	0.5221	0.0018
WNT10B		It blocks brown adipose tissue development and expression of UCP-1.	0.7189	<0.0001
RB1		Molecular switch determining white vs. brown adipogenesis	0.5211	0.0019
NR0B2		A negative regulator of PGC-1α expression in brown adipocytes	0.8780	<0.0001
GATA2	Anti-white adipose tissue	Suppressor of adipocyte differentiation	0.6982	<0.0001
GATA3		Involved in white browning	0.4522	0.0082
KLF2		Negative regulator of adipogenesis	0.4318	0.0121
KLF3		Induction of Wnt10b and KLF3 decrease PPARγ expression	0.6765	<0.0001
IRS2	Pro-adipogenesis	Promoter of adipocyte differentiation	0.6517	<0.0001
CEBPB			0.4369	0.0110
FGF1			0.3830	0.0278
SFRP5			0.6130	0.0001
WNT5B			0.3917	0.0242
CREB1	Pro-brown adipose tissue	Involved in the transcriptional regulation of brown adipogenesis	−0.4830	0.0044
FOXC2			0.8443	<0.0001
MAPK14			0.3981	0.0218
PPARA		Regulators of brown adipogenesis/metabolism	0.7383	<0.0001
PPARD			0.8281	<0.0001
PPARGC1A			0.6832	<0.0001
UCP-1			0.5635	0.0006
PRDM16			0.7189	<0.0001
SRC		Controls brown fat thermogenesis	0.4412	0.0102
BMP7	Pro-white adipose tissue	Promoters of white adipogenesis	0.5625	<0.0007
KLF15	Pro-white adipose tissue	Promoters of white adipogenesis	0.6768	<0.0001

Spearman correlation coefficients and corresponding P value are reported.

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