Entry
Name
Thermogenesis - Homo sapiens (human)
Description
Thermogenesis is essential for warm-blooded animals, ensuring normal cellular and physiological function under conditions of environmental challenge. Thermogenesis in brown and beige adipose tissue is mainly controlled by norepinephrine, which is released from sympathetic nervous system in response to cold or dietary stimuli. The mitochondrial uncoupling protein 1 (UCP1) is responsible for the process whereby chemical energy is converted into heat in these adipocytes. Activation of these adipocytes leads to an increase in calorie consumption and is expected to improve overweight conditions, providing a potential strategy for treating obesity and its related metabolic disorders.
Class
Organismal Systems; Environmental adaptation
BRITE hierarchy
Pathway map
Ortholog table
Network
Element
N01688 ADRB3-UCP1 signaling pathway
N01691 mitochondrial complex - UCP1 in Thermogenesis
Drug
D12264 Bomedemstat tosylate (USAN)
D12490 Fazpilodemab (USAN/INN)
D12577 Seclidemstat (USAN/INN)
D12578 Seclidemstat mesylate (USAN)
Other DBs
Organism
Homo sapiens (human) [GN:
hsa ]
Gene
1385 CREB1; cAMP responsive element binding protein 1 [KO:K05870 ]
10488 CREB3; cAMP responsive element binding protein 3 [KO:K09048 ]
90993 CREB3L1; cAMP responsive element binding protein 3 like 1 [KO:K09048 ]
64764 CREB3L2; cAMP responsive element binding protein 3 like 2 [KO:K09048 ]
84699 CREB3L3; cAMP responsive element binding protein 3 like 3 [KO:K09048 ]
148327 CREB3L4; cAMP responsive element binding protein 3 like 4 [KO:K09048 ]
9586 CREB5; cAMP responsive element binding protein 5 [KO:K09047 ]
6595 SMARCA2; SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 2 [KO:K11647 ] [EC:5.6.2.-]
6597 SMARCA4; SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4 [KO:K11647 ] [EC:5.6.2.-]
6598 SMARCB1; SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily b, member 1 [KO:K11648 ]
6599 SMARCC1; SWI/SNF related, matrix associated, actin dependent regulator of chromatin subfamily c member 1 [KO:K11649 ]
6601 SMARCC2; SWI/SNF related, matrix associated, actin dependent regulator of chromatin subfamily c member 2 [KO:K11649 ]
6602 SMARCD1; SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily d, member 1 [KO:K11650 ]
6603 SMARCD2; SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily d, member 2 [KO:K11650 ]
6604 SMARCD3; SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily d, member 3 [KO:K11650 ]
6605 SMARCE1; SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily e, member 1 [KO:K11651 ]
57492 ARID1B; AT-rich interaction domain 1B [KO:K11653 ]
8289 ARID1A; AT-rich interaction domain 1A [KO:K11653 ]
5468 PPARG; peroxisome proliferator activated receptor gamma [KO:K08530 ]
1386 ATF2; activating transcription factor 2 [KO:K04450 ]
5564 PRKAB1; protein kinase AMP-activated non-catalytic subunit beta 1 [KO:K07199 ]
5565 PRKAB2; protein kinase AMP-activated non-catalytic subunit beta 2 [KO:K07199 ]
5571 PRKAG1; protein kinase AMP-activated non-catalytic subunit gamma 1 [KO:K07200 ]
53632 PRKAG3; protein kinase AMP-activated non-catalytic subunit gamma 3 [KO:K07200 ]
51422 PRKAG2; protein kinase AMP-activated non-catalytic subunit gamma 2 [KO:K07200 ]
656 BMP8B; bone morphogenetic protein 8b [KO:K16622 ]
10818 FRS2; fibroblast growth factor receptor substrate 2 [KO:K12461 ]
2885 GRB2; growth factor receptor bound protein 2 [KO:K04364 ]
6654 SOS1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099 ]
6655 SOS2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099 ]
3265 HRAS; HRas proto-oncogene, GTPase [KO:K02833 ]
3845 KRAS; KRAS proto-oncogene, GTPase [KO:K07827 ]
4893 NRAS; NRAS proto-oncogene, GTPase [KO:K07828 ]
6009 RHEB; Ras homolog, mTORC1 binding [KO:K07208 ]
57521 RPTOR; regulatory associated protein of MTOR complex 1 [KO:K07204 ]
64223 MLST8; MTOR associated protein, LST8 homolog [KO:K08266 ]
4724 NDUFS4; NADH:ubiquinone oxidoreductase subunit S4 [KO:K03937 ]
4725 NDUFS5; NADH:ubiquinone oxidoreductase subunit S5 [KO:K03938 ]
4726 NDUFS6; NADH:ubiquinone oxidoreductase subunit S6 [KO:K03939 ]
4731 NDUFV3; NADH:ubiquinone oxidoreductase subunit V3 [KO:K03944 ]
4694 NDUFA1; NADH:ubiquinone oxidoreductase subunit A1 [KO:K03945 ]
4695 NDUFA2; NADH:ubiquinone oxidoreductase subunit A2 [KO:K03946 ]
4696 NDUFA3; NADH:ubiquinone oxidoreductase subunit A3 [KO:K03947 ]
4697 NDUFA4; NDUFA4 mitochondrial complex associated [KO:K03948 ]
56901 NDUFA4L2; NDUFA4 mitochondrial complex associated like 2 [KO:K03948 ]
4698 NDUFA5; NADH:ubiquinone oxidoreductase subunit A5 [KO:K03949 ]
4700 NDUFA6; NADH:ubiquinone oxidoreductase subunit A6 [KO:K03950 ]
4701 NDUFA7; NADH:ubiquinone oxidoreductase subunit A7 [KO:K03951 ]
4702 NDUFA8; NADH:ubiquinone oxidoreductase subunit A8 [KO:K03952 ]
4704 NDUFA9; NADH:ubiquinone oxidoreductase subunit A9 [KO:K03953 ]
4705 NDUFA10; NADH:ubiquinone oxidoreductase subunit A10 [KO:K03954 ]
4706 NDUFAB1; NADH:ubiquinone oxidoreductase subunit AB1 [KO:K03955 ]
126328 NDUFA11; NADH:ubiquinone oxidoreductase subunit A11 [KO:K03956 ]
55967 NDUFA12; NADH:ubiquinone oxidoreductase subunit A12 [KO:K11352 ]
51079 NDUFA13; NADH:ubiquinone oxidoreductase subunit A13 [KO:K11353 ]
4707 NDUFB1; NADH:ubiquinone oxidoreductase subunit B1 [KO:K03957 ]
4708 NDUFB2; NADH:ubiquinone oxidoreductase subunit B2 [KO:K03958 ]
4709 NDUFB3; NADH:ubiquinone oxidoreductase subunit B3 [KO:K03959 ]
4710 NDUFB4; NADH:ubiquinone oxidoreductase subunit B4 [KO:K03960 ]
4711 NDUFB5; NADH:ubiquinone oxidoreductase subunit B5 [KO:K03961 ]
4712 NDUFB6; NADH:ubiquinone oxidoreductase subunit B6 [KO:K03962 ]
4713 NDUFB7; NADH:ubiquinone oxidoreductase subunit B7 [KO:K03963 ]
4714 NDUFB8; NADH:ubiquinone oxidoreductase subunit B8 [KO:K03964 ]
4715 NDUFB9; NADH:ubiquinone oxidoreductase subunit B9 [KO:K03965 ]
4716 NDUFB10; NADH:ubiquinone oxidoreductase subunit B10 [KO:K03966 ]
54539 NDUFB11; NADH:ubiquinone oxidoreductase subunit B11 [KO:K11351 ]
4717 NDUFC1; NADH:ubiquinone oxidoreductase subunit C1 [KO:K03967 ]
4718 NDUFC2; NADH:ubiquinone oxidoreductase subunit C2 [KO:K03968 ]
51103 NDUFAF1; NADH:ubiquinone oxidoreductase complex assembly factor 1 [KO:K18159 ]
91942 NDUFAF2; NADH:ubiquinone oxidoreductase complex assembly factor 2 [KO:K18160 ]
25915 NDUFAF3; NADH:ubiquinone oxidoreductase complex assembly factor 3 [KO:K09008 ]
29078 NDUFAF4; NADH:ubiquinone oxidoreductase complex assembly factor 4 [KO:K18161 ]
79133 NDUFAF5; NADH:ubiquinone oxidoreductase complex assembly factor 5 [KO:K18162 ] [EC:2.1.1.-]
137682 NDUFAF6; NADH:ubiquinone oxidoreductase complex assembly factor 6 [KO:K18163 ]
55471 NDUFAF7; NADH:ubiquinone oxidoreductase complex assembly factor 7 [KO:K18164 ]
284184 NDUFAF8; NADH:ubiquinone oxidoreductase complex assembly factor 8 [KO:K24726 ]
6389 SDHA; succinate dehydrogenase complex flavoprotein subunit A [KO:K00234 ] [EC:1.3.5.1 ]
6390 SDHB; succinate dehydrogenase complex iron sulfur subunit B [KO:K00235 ] [EC:1.3.5.1 ]
6391 SDHC; succinate dehydrogenase complex subunit C [KO:K00236 ]
6392 SDHD; succinate dehydrogenase complex subunit D [KO:K00237 ]
7386 UQCRFS1; ubiquinol-cytochrome c reductase, Rieske iron-sulfur polypeptide 1 [KO:K00411 ] [EC:7.1.1.8 ]
7384 UQCRC1; ubiquinol-cytochrome c reductase core protein 1 [KO:K00414 ]
7385 UQCRC2; ubiquinol-cytochrome c reductase core protein 2 [KO:K00415 ]
7388 UQCRH; ubiquinol-cytochrome c reductase hinge protein [KO:K00416 ]
440567 UQCRHL; ubiquinol-cytochrome c reductase hinge protein like [KO:K00416 ]
7381 UQCRB; ubiquinol-cytochrome c reductase binding protein [KO:K00417 ]
27089 UQCRQ; ubiquinol-cytochrome c reductase complex III subunit VII [KO:K00418 ]
29796 UQCR10; ubiquinol-cytochrome c reductase, complex III subunit X [KO:K00419 ]
10975 UQCR11; ubiquinol-cytochrome c reductase, complex III subunit XI [KO:K00420 ]
4513 COX2; cytochrome c oxidase subunit II [KO:K02261 ]
4514 COX3; cytochrome c oxidase subunit III [KO:K02262 ]
84701 COX4I2; cytochrome c oxidase subunit 4I2 [KO:K02263 ]
1327 COX4I1; cytochrome c oxidase subunit 4I1 [KO:K02263 ]
9377 COX5A; cytochrome c oxidase subunit 5A [KO:K02264 ]
1329 COX5B; cytochrome c oxidase subunit 5B [KO:K02265 ]
1337 COX6A1; cytochrome c oxidase subunit 6A1 [KO:K02266 ]
1339 COX6A2; cytochrome c oxidase subunit 6A2 [KO:K02266 ]
1340 COX6B1; cytochrome c oxidase subunit 6B1 [KO:K02267 ]
1345 COX6C; cytochrome c oxidase subunit 6C [KO:K02268 ]
1346 COX7A1; cytochrome c oxidase subunit 7A1 [KO:K02270 ]
1347 COX7A2; cytochrome c oxidase subunit 7A2 [KO:K02270 ]
9167 COX7A2L; cytochrome c oxidase subunit 7A2 like [KO:K02270 ]
1349 COX7B; cytochrome c oxidase subunit 7B [KO:K02271 ]
1350 COX7C; cytochrome c oxidase subunit 7C [KO:K02272 ]
1351 COX8A; cytochrome c oxidase subunit 8A [KO:K02273 ]
1352 COX10; cytochrome c oxidase assembly factor heme A:farnesyltransferase COX10 [KO:K02257 ] [EC:2.5.1.141 ]
1353 COX11; cytochrome c oxidase copper chaperone COX11 [KO:K02258 ]
84987 COX14; cytochrome c oxidase assembly factor COX14 [KO:K18181 ]
51241 COX16; cytochrome c oxidase assembly factor COX16 [KO:K18182 ]
10063 COX17; cytochrome c oxidase copper chaperone COX17 [KO:K02260 ]
285521 COX18; cytochrome c oxidase assembly factor COX18 [KO:K17797 ]
90639 COX19; cytochrome c oxidase assembly factor COX19 [KO:K18183 ]
116228 COX20; cytochrome c oxidase assembly factor COX20 [KO:K18184 ]
55744 COA1; cytochrome c oxidase assembly factor 1 [KO:K18173 ]
28958 COA3; cytochrome c oxidase assembly factor 3 [KO:K18175 ]
51287 COA4; cytochrome c oxidase assembly factor 4 homolog [KO:K18177 ]
493753 COA5; cytochrome c oxidase assembly factor 5 [KO:K18178 ]
388753 COA6; cytochrome c oxidase assembly factor 6 [KO:K18179 ]
65260 COA7; cytochrome c oxidase assembly factor 7 [KO:K18180 ]
498 ATP5F1A; ATP synthase F1 subunit alpha [KO:K02132 ]
509 ATP5F1C; ATP synthase F1 subunit gamma [KO:K02136 ]
513 ATP5F1D; ATP synthase F1 subunit delta [KO:K02134 ]
514 ATP5F1E; ATP synthase F1 subunit epsilon [KO:K02135 ]
539 ATP5PO; ATP synthase peripheral stalk subunit OSCP [KO:K02137 ]
515 ATP5PB; ATP synthase peripheral stalk-membrane subunit b [KO:K02127 ]
516 ATP5MC1; ATP synthase membrane subunit c locus 1 [KO:K02128 ]
517 ATP5MC2; ATP synthase membrane subunit c locus 2 [KO:K02128 ]
518 ATP5MC3; ATP synthase membrane subunit c locus 3 [KO:K02128 ]
10476 ATP5PD; ATP synthase peripheral stalk subunit d [KO:K02138 ]
521 ATP5ME; ATP synthase membrane subunit e [KO:K02129 ]
9551 ATP5MF; ATP synthase membrane subunit f [KO:K02130 ]
522 ATP5PF; ATP synthase peripheral stalk subunit F6 [KO:K02131 ]
10632 ATP5MG; ATP synthase membrane subunit g [KO:K02140 ]
123096 SLC25A29; solute carrier family 25 member 29 [KO:K15109 ]
788 SLC25A20; solute carrier family 25 member 20 [KO:K15109 ]
Compound
Reference
Authors
Inagaki T, Sakai J, Kajimura S
Title
Transcriptional and epigenetic control of brown and beige adipose cell fate and function.
Journal
Reference
Authors
Harms M, Seale P
Title
Brown and beige fat: development, function and therapeutic potential.
Journal
Reference
Authors
Boon MR, Kooijman S, van Dam AD, Pelgrom LR, Berbee JF, Visseren CA, van Aggele RC, van den Hoek AM, Sips HC, Lombes M, Havekes LM, Tamsma JT, Guigas B, Meijer OC, Jukema JW, Rensen PC
Title
Peripheral cannabinoid 1 receptor blockade activates brown adipose tissue and diminishes dyslipidemia and obesity.
Journal
Reference
Authors
Merlin J, Evans BA, Dehvari N, Sato M, Bengtsson T, Hutchinson DS
Title
Could burning fat start with a brite spark? Pharmacological and nutritional ways to promote thermogenesis.
Journal
Reference
Authors
van Dam AD, Kooijman S, Schilperoort M, Rensen PC, Boon MR
Title
Regulation of brown fat by AMP-activated protein kinase.
Journal
Reference
Authors
Kooijman S, van den Heuvel JK, Rensen PC
Title
Neuronal Control of Brown Fat Activity.
Journal
Reference
Authors
Contreras C, Nogueiras R, Dieguez C, Rahmouni K, Lopez M
Title
Traveling from the hypothalamus to the adipose tissue: The thermogenic pathway.
Journal
Reference
Authors
Fruhbeck G, Mendez-Gimenez L, Fernandez-Formoso JA, Fernandez S, Rodriguez A
Title
Regulation of adipocyte lipolysis.
Journal
Reference
Authors
Tansey JT, Sztalryd C, Hlavin EM, Kimmel AR, Londos C
Title
The central role of perilipin a in lipid metabolism and adipocyte lipolysis.
Journal
Reference
Authors
Collins S, Yehuda-Shnaidman E, Wang H
Title
Positive and negative control of Ucp1 gene transcription and the role of beta-adrenergic signaling networks.
Journal
Reference
Authors
Robidoux J, Cao W, Quan H, Daniel KW, Moukdar F, Bai X, Floering LM, Collins S
Title
Selective activation of mitogen-activated protein (MAP) kinase kinase 3 and p38alpha MAP kinase is essential for cyclic AMP-dependent UCP1 expression in adipocytes.
Journal
Reference
Authors
Hattori K, Naguro I, Okabe K, Funatsu T, Furutani S, Takeda K, Ichijo H
Title
ASK1 signalling regulates brown and beige adipocyte function.
Journal
Reference
Authors
Abe Y, Rozqie R, Matsumura Y, Kawamura T, Nakaki R, Tsurutani Y, Tanimura-Inagaki K, Shiono A, Magoori K, Nakamura K, Ogi S, Kajimura S, Kimura H, Tanaka T, Fukami K, Osborne TF, Kodama T, Aburatani H, Inagaki T, Sakai J
Title
JMJD1A is a signal-sensing scaffold that regulates acute chromatin dynamics via SWI/SNF association for thermogenesis.
Journal
Reference
Authors
Dempersmier J, Sambeat A, Gulyaeva O, Paul SM, Hudak CS, Raposo HF, Kwan HY, Kang C, Wong RH, Sul HS
Title
Cold-inducible Zfp516 activates UCP1 transcription to promote browning of white fat and development of brown fat.
Journal
Reference
Authors
Sambeat A, Gulyaeva O, Dempersmier J, Tharp KM, Stahl A, Paul SM, Sul HS
Title
LSD1 Interacts with Zfp516 to Promote UCP1 Transcription and Brown Fat Program.
Journal
Reference
Authors
Villarroya F, Peyrou M, Giralt M
Title
Transcriptional regulation of the uncoupling protein-1 gene.
Journal
Reference
Authors
Cao W, Daniel KW, Robidoux J, Puigserver P, Medvedev AV, Bai X, Floering LM, Spiegelman BM, Collins S
Title
p38 mitogen-activated protein kinase is the central regulator of cyclic AMP-dependent transcription of the brown fat uncoupling protein 1 gene.
Journal
Reference
Authors
Hondares E, Iglesias R, Giralt A, Gonzalez FJ, Giralt M, Mampel T, Villarroya F
Title
Thermogenic activation induces FGF21 expression and release in brown adipose tissue.
Journal
Reference
Authors
Yao L, Cui X, Chen Q, Yang X, Fang F, Zhang J, Liu G, Jin W, Chang Y
Title
Cold-Inducible SIRT6 Regulates Thermogenesis of Brown and Beige Fat.
Journal
Reference
Authors
Klingenberg M
Title
UCP1 - A sophisticated energy valve.
Journal
Reference
Authors
Bertholet AM, Kirichok Y
Title
UCP1: A transporter for H(+) and fatty acid anions.
Journal
Reference
Authors
Betz MJ, Enerback S
Title
Targeting thermogenesis in brown fat and muscle to treat obesity and metabolic disease.
Journal
Reference
Authors
Tseng YH, Cypess AM, Kahn CR
Title
Cellular bioenergetics as a target for obesity therapy.
Journal
Reference
Authors
Fenzl A, Kiefer FW
Title
Brown adipose tissue and thermogenesis.
Journal
Reference
Authors
Minard AY, Tan SX, Yang P, Fazakerley DJ, Domanova W, Parker BL, Humphrey SJ, Jothi R, Stockli J, James DE
Title
mTORC1 Is a Major Regulatory Node in the FGF21 Signaling Network in Adipocytes.
Journal
Reference
Authors
Fisher FM, Kleiner S, Douris N, Fox EC, Mepani RJ, Verdeguer F, Wu J, Kharitonenkov A, Flier JS, Maratos-Flier E, Spiegelman BM
Title
FGF21 regulates PGC-1alpha and browning of white adipose tissues in adaptive thermogenesis.
Journal
Reference
Authors
Zois NE, Bartels ED, Hunter I, Kousholt BS, Olsen LH, Goetze JP
Title
Natriuretic peptides in cardiometabolic regulation and disease.
Journal
Reference
Authors
Indiveri C, Iacobazzi V, Tonazzi A, Giangregorio N, Infantino V, Convertini P, Console L, Palmieri F
Title
The mitochondrial carnitine/acylcarnitine carrier: function, structure and physiopathology.
Journal
Reference
Authors
McCoin CS, Knotts TA, Adams SH
Title
Acylcarnitines--old actors auditioning for new roles in metabolic physiology.
Journal
Reference
Authors
Ohtomo T, Ino K, Miyashita R, Chigira M, Nakamura M, Someya K, Inaba N, Fujita M, Takagi M, Yamada J
Title
Chronic high-fat feeding impairs adaptive induction of mitochondrial fatty acid combustion-associated proteins in brown adipose tissue of mice.
Journal
Related pathway
hsa04923 Regulation of lipolysis in adipocytes
KO pathway
LinkDB
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