ENTRY ko04714 Pathway NAME Thermogenesis 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 PATHWAY_MAP ko04714 Thermogenesis DBLINKS GO: 1990845 ORTHOLOGY K00234 SDHA, SDH1; succinate dehydrogenase (ubiquinone) flavoprotein subunit [EC:1.3.5.1] K00235 SDHB, SDH2; succinate dehydrogenase (ubiquinone) iron-sulfur subunit [EC:1.3.5.1] K00236 SDHC, SDH3; succinate dehydrogenase (ubiquinone) cytochrome b560 subunit K00237 SDHD, SDH4; succinate dehydrogenase (ubiquinone) membrane anchor subunit K00411 UQCRFS1, RIP1, petA; ubiquinol-cytochrome c reductase iron-sulfur subunit [EC:7.1.1.8] K00412 CYTB, petB; ubiquinol-cytochrome c reductase cytochrome b subunit K00413 CYC1, CYT1, petC; ubiquinol-cytochrome c reductase cytochrome c1 subunit K00414 QCR1, UQCRC1; ubiquinol-cytochrome c reductase core subunit 1 K00415 QCR2, UQCRC2; ubiquinol-cytochrome c reductase core subunit 2 K00416 QCR6, UQCRH; ubiquinol-cytochrome c reductase subunit 6 K00417 QCR7, UQCRB; ubiquinol-cytochrome c reductase subunit 7 K00418 QCR8, UQCRQ; ubiquinol-cytochrome c reductase subunit 8 K00419 QCR9, UCRC; ubiquinol-cytochrome c reductase subunit 9 K00420 QCR10, UQCR; ubiquinol-cytochrome c reductase subunit 10 K01054 MGLL; acylglycerol lipase [EC:3.1.1.23] K01897 ACSL, fadD; long-chain-fatty-acid---CoA ligase [EC:6.2.1.3] K02125 ATPeF08, MTATP8, ATP8; F-type H+-transporting ATPase subunit 8 K02126 ATPeF0A, MTATP6, ATP6; F-type H+-transporting ATPase subunit a K02127 ATPeF0B, ATP5F1, ATP4; F-type H+-transporting ATPase subunit b K02128 ATPeF0C, ATP5G, ATP9; F-type H+-transporting ATPase subunit c K02129 ATPeF0E, ATP5I; F-type H+-transporting ATPase subunit e K02130 ATPeF0F, ATP5J2; F-type H+-transporting ATPase subunit f K02131 ATPeF0F6, ATP5J; F-type H+-transporting ATPase subunit 6 K02132 ATPeF1A, ATP5A1, ATP1; F-type H+-transporting ATPase subunit alpha K02133 ATPeF1B, ATP5B, ATP2; F-type H+-transporting ATPase subunit beta [EC:7.1.2.2] K02134 ATPeF1D, ATP5D, ATP16; F-type H+-transporting ATPase subunit delta K02135 ATPeF1E, ATP5E, ATP15; F-type H+-transporting ATPase subunit epsilon K02136 ATPeF1G, ATP5C1, ATP3; F-type H+-transporting ATPase subunit gamma K02137 ATPeF0O, ATP5O, ATP5; F-type H+-transporting ATPase subunit O K02138 ATPeF0D, ATP5H, ATP7; F-type H+-transporting ATPase subunit d K02140 ATPeFG, ATP5L, ATP20; F-type H+-transporting ATPase subunit g K02256 COX1; cytochrome c oxidase subunit 1 [EC:7.1.1.9] K02257 COX10, ctaB, cyoE; heme o synthase [EC:2.5.1.141] K02258 COX11, ctaG; cytochrome c oxidase assembly protein subunit 11 K02259 COX15, ctaA; heme a synthase [EC:1.17.99.9] K02260 COX17; cytochrome c oxidase assembly protein subunit 17 K02261 COX2; cytochrome c oxidase subunit 2 K02262 COX3; cytochrome c oxidase subunit 3 K02263 COX4; cytochrome c oxidase subunit 4 K02264 COX5A; cytochrome c oxidase subunit 5a K02265 COX5B; cytochrome c oxidase subunit 5b K02266 COX6A; cytochrome c oxidase subunit 6a K02267 COX6B; cytochrome c oxidase subunit 6b K02268 COX6C; cytochrome c oxidase subunit 6c K02270 COX7A; cytochrome c oxidase subunit 7a K02271 COX7B; cytochrome c oxidase subunit 7b K02272 COX7C; cytochrome c oxidase subunit 7c K02273 COX8; cytochrome c oxidase subunit 8 K02833 HRAS; GTPase HRas K02991 RP-S6e, RPS6; small subunit ribosomal protein S6e K03099 SOS; son of sevenless K03878 ND1; NADH-ubiquinone oxidoreductase chain 1 [EC:7.1.1.2] K03879 ND2; NADH-ubiquinone oxidoreductase chain 2 [EC:7.1.1.2] K03880 ND3; NADH-ubiquinone oxidoreductase chain 3 [EC:7.1.1.2] K03881 ND4; NADH-ubiquinone oxidoreductase chain 4 [EC:7.1.1.2] K03882 ND4L; NADH-ubiquinone oxidoreductase chain 4L [EC:7.1.1.2] K03883 ND5; NADH-ubiquinone oxidoreductase chain 5 [EC:7.1.1.2] K03884 ND6; NADH-ubiquinone oxidoreductase chain 6 [EC:7.1.1.2] K03934 NDUFS1; NADH dehydrogenase (ubiquinone) Fe-S protein 1 [EC:7.1.1.2] K03935 NDUFS2; NADH dehydrogenase (ubiquinone) Fe-S protein 2 [EC:7.1.1.2] K03936 NDUFS3; NADH dehydrogenase (ubiquinone) Fe-S protein 3 [EC:7.1.1.2] K03937 NDUFS4; NADH dehydrogenase (ubiquinone) Fe-S protein 4 K03938 NDUFS5; NADH dehydrogenase (ubiquinone) Fe-S protein 5 K03939 NDUFS6; NADH dehydrogenase (ubiquinone) Fe-S protein 6 K03940 NDUFS7; NADH dehydrogenase (ubiquinone) Fe-S protein 7 [EC:7.1.1.2] K03941 NDUFS8; NADH dehydrogenase (ubiquinone) Fe-S protein 8 [EC:7.1.1.2] K03942 NDUFV1; NADH dehydrogenase (ubiquinone) flavoprotein 1 [EC:7.1.1.2] K03943 NDUFV2; NADH dehydrogenase (ubiquinone) flavoprotein 2 [EC:7.1.1.2] K03944 NDUFV3; NADH dehydrogenase (ubiquinone) flavoprotein 3 K03945 NDUFA1; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex subunit 1 K03946 NDUFA2; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex subunit 2 K03947 NDUFA3; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex subunit 3 K03948 NDUFA4; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex subunit 4 K03949 NDUFA5; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex subunit 5 K03950 NDUFA6; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex subunit 6 K03951 NDUFA7; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex subunit 7 K03952 NDUFA8; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex subunit 8 K03953 NDUFA9; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex subunit 9 K03954 NDUFA10; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex subunit 10 K03955 NDUFAB1; NADH dehydrogenase (ubiquinone) 1 alpha/beta subcomplex 1, acyl-carrier protein K03956 NDUFA11; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex subunit 11 K03957 NDUFB1; NADH dehydrogenase (ubiquinone) 1 beta subcomplex subunit 1 K03958 NDUFB2; NADH dehydrogenase (ubiquinone) 1 beta subcomplex subunit 2 K03959 NDUFB3; NADH dehydrogenase (ubiquinone) 1 beta subcomplex subunit 3 K03960 NDUFB4; NADH dehydrogenase (ubiquinone) 1 beta subcomplex subunit 4 K03961 NDUFB5; NADH dehydrogenase (ubiquinone) 1 beta subcomplex subunit 5 K03962 NDUFB6; NADH dehydrogenase (ubiquinone) 1 beta subcomplex subunit 6 K03963 NDUFB7; NADH dehydrogenase (ubiquinone) 1 beta subcomplex subunit 7 K03964 NDUFB8; NADH dehydrogenase (ubiquinone) 1 beta subcomplex subunit 8 K03965 NDUFB9; NADH dehydrogenase (ubiquinone) 1 beta subcomplex subunit 9 K03966 NDUFB10; NADH dehydrogenase (ubiquinone) 1 beta subcomplex subunit 10 K03967 NDUFC1; NADH dehydrogenase (ubiquinone) 1 subunit C1 K03968 NDUFC2; NADH dehydrogenase (ubiquinone) 1 subunit C2 K04143 ADRB3; adrenergic receptor beta-3 K04277 CNR1; cannabinoid receptor 1 K04345 PKA; protein kinase A [EC:2.7.11.11] K04362 FGFR1, CD331; fibroblast growth factor receptor 1 [EC:2.7.10.1] K04364 GRB2; growth factor receptor-bound protein 2 K04373 RPS6KA; ribosomal protein S6 kinase alpha-1/2/3/6 [EC:2.7.11.1] K04426 MAP3K5, ASK1; mitogen-activated protein kinase kinase kinase 5 [EC:2.7.11.25] K04432 MAP2K3, MKK3; mitogen-activated protein kinase kinase 3 [EC:2.7.12.2] K04441 P38; p38 MAP kinase [EC:2.7.11.24] K04450 ATF2, CREBP1; cyclic AMP-dependent transcription factor ATF-2 K04632 GNAS; guanine nucleotide-binding protein G(s) subunit alpha K04688 RPS6KB; ribosomal protein S6 kinase beta [EC:2.7.11.1] K05259 GCG; glucagon K05692 ACTB_G1; actin beta/gamma 1 K05870 CREB1; cyclic AMP-responsive element-binding protein 1 K07188 LIPE, HSL; hormone-sensitive lipase [EC:3.1.1.79] K07198 PRKAA, AMPK; 5'-AMP-activated protein kinase, catalytic alpha subunit [EC:2.7.11.31] K07199 PRKAB; 5'-AMP-activated protein kinase, regulatory beta subunit K07200 PRKAG; 5'-AMP-activated protein kinase, regulatory gamma subunit K07202 PPARGC1A, PGC1A; alpha peroxisome proliferator-activated receptor gamma coactivator 1-alpha K07203 MTOR, FRAP, TOR; serine/threonine-protein kinase mTOR [EC:2.7.11.1] K07204 RAPTOR; regulatory associated protein of mTOR K07206 TSC1; tuberous sclerosis 1 K07207 TSC2; tuberous sclerosis 2 K07208 RHEB; Ras homolog enriched in brain K07376 PRKG1; cGMP-dependent protein kinase 1 [EC:2.7.11.12] K07827 KRAS, KRAS2; GTPase KRas K07828 NRAS; GTPase NRas K08041 ADCY1; adenylate cyclase 1 [EC:4.6.1.1] K08042 ADCY2; adenylate cyclase 2 [EC:4.6.1.1] K08043 ADCY3; adenylate cyclase 3 [EC:4.6.1.1] K08044 ADCY4; adenylate cyclase 4 [EC:4.6.1.1] K08045 ADCY5; adenylate cyclase 5 [EC:4.6.1.1] K08046 ADCY6; adenylate cyclase 6 [EC:4.6.1.1] K08047 ADCY7; adenylate cyclase 7 [EC:4.6.1.1] K08048 ADCY8; adenylate cyclase 8 [EC:4.6.1.1] K08049 ADCY9; adenylate cyclase 9 [EC:4.6.1.1] K08266 MLST8, GBL; target of rapamycin complex subunit LST8 K08530 NR1C3, PPARG; peroxisome proliferator-activated receptor gamma K08765 CPT1A; carnitine O-palmitoyltransferase 1, liver isoform [EC:2.3.1.21] K08766 CPT2; carnitine O-palmitoyltransferase 2 [EC:2.3.1.21] K08768 PLIN1; perilipin-1 K08769 UCP1, SLC25A7; solute carrier family 25 (mitochondrial uncoupling protein), member 7 K09008 NDUFAF3; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex assembly factor 3 K09047 CREB5, CREBPA; cyclic AMP-responsive element-binding protein 5 K09048 CREB3; cyclic AMP-responsive element-binding protein 3 K11265 ADCY10; adenylate cyclase 10 [EC:4.6.1.1] K11340 ACTL6A, INO80K; actin-like protein 6A K11351 NDUFB11; NADH dehydrogenase (ubiquinone) 1 beta subcomplex subunit 11 K11352 NDUFA12; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex subunit 12 K11353 NDUFA13; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex subunit 13 K11416 SIRT6, SIR2L6; NAD-dependent protein deacetylase sirtuin 6 [EC:2.3.1.286] K11450 KDM1A, AOF2, LSD1; [histone H3]-N6,N6-dimethyl-L-lysine4 FAD-dependent demethylase [EC:1.14.99.66] K11647 SMARCA2_4; SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 2/4 [EC:5.6.2.-] K11648 SMARCB1, SNF5, INI1; SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 K11649 SMARCC; SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily C K11650 SMARCD; SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily D K11651 SMARCE1; SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1 K11652 ACTL6B; actin-like protein 6B K11653 ARID1; AT-rich interactive domain-containing protein 1 K12323 NPR1, ANPRA; atrial natriuretic peptide receptor 1 [EC:4.6.1.2] K12334 NPPA; natriuretic peptide A K12335 NPPB; natriuretic peptide B K12461 FRS2; fibroblast growth factor receptor substrate 2 K15109 SLC25A20, CACT, CAC, CRC1; solute carrier family 25 (mitochondrial carnitine/acylcarnitine transporter), member 20 K15601 KDM3; [histone H3]-dimethyl-L-lysine9 demethylase [EC:1.14.11.65] K16184 AKT1S1, PRAS40; proline-rich AKT1 substrate 1 K16622 BMP8; bone morphogenetic protein 8 K16816 PNPLA2, ATGL; patatin-like phospholipase domain-containing protein 2 [EC:3.1.1.3] K17797 COX18; mitochondrial inner membrane protein COX18 K18159 NDUFAF1, CIA30; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex assembly factor 1 K18160 NDUFAF2; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex assembly factor 2 K18161 NDUFAF4; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex assembly factor 4 K18162 NDUFAF5; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex assembly factor 5 [EC:2.1.1.-] K18163 NDUFAF6; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex assembly factor 6 K18164 NDUFAF7; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex assembly factor 7 K18173 COA1; cytochrome c oxidase assembly factor 1 K18175 CCDC56, COA3; cytochrome c oxidase assembly factor 3, animal type K18177 COA4; cytochrome c oxidase assembly factor 4 K18178 COA5, PET191; cytochrome c oxidase assembly factor 5 K18179 COA6; cytochrome c oxidase assembly factor 6 K18180 COA7, SELRC1, RESA1; cytochrome c oxidase assembly factor 7 K18181 COX14; cytochrome c oxidase assembly factor 14 K18182 COX16; cytochrome c oxidase assembly protein subunit 16 K18183 COX19; cytochrome c oxidase assembly protein subunit 19 K18184 COX20; cytochrome c oxidase assembly protein subunit 20 K19477 PRKG2; cGMP-dependent protein kinase 2 [EC:2.7.11.12] K19523 CPT1B; carnitine O-palmitoyltransferase 1, muscle isoform [EC:2.3.1.21] K19524 CPT1C; carnitine O-palmitoyltransferase 1, brain isoform [EC:2.3.1.21] K22198 DPF1_3; zinc finger protein neuro-d4/cer-d4 K22404 KLB; beta-klotho K22410 PRDM16; [histone H3]-lysine9 N-methyltransferase [EC:2.1.1.367] K22411 ZNF516; zinc finger protein 516 K22429 FGF21; fibroblast growth factor 21 K24726 NDUFAF8; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex assembly factor 8 COMPOUND C00002 ATP C00004 NADH C00008 ADP C00010 CoA C00024 Acetyl-CoA C00040 Acyl-CoA C00080 H+ C00116 Glycerol C00162 Fatty acid C00165 Diacylglycerol C00318 L-Carnitine C00422 Triacylglycerol C00547 L-Noradrenaline C00575 3',5'-Cyclic AMP C00745 Nicotine C00942 3',5'-Cyclic GMP C00951 Estradiol-17beta C01352 FADH2 C01885 1-Acylglycerol C02301 O-Acylcarnitine C02465 Triiodothyronine C11695 Anandamide C13856 2-Arachidonoylglycerol REFERENCE PMID:27251423 AUTHORS Inagaki T, Sakai J, Kajimura S TITLE Transcriptional and epigenetic control of brown and beige adipose cell fate and function. JOURNAL Nat Rev Mol Cell Biol 17:480-95 (2016) DOI:10.1038/nrm.2016.62 REFERENCE PMID:24100998 AUTHORS Harms M, Seale P TITLE Brown and beige fat: development, function and therapeutic potential. JOURNAL Nat Med 19:1252-63 (2013) DOI:10.1038/nm.3361 REFERENCE PMID:25154875 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 FASEB J 28:5361-75 (2014) DOI:10.1096/fj.13-247643 REFERENCE PMID:26201764 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. 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JOURNAL Mol Aspects Med 32:223-33 (2011) DOI:10.1016/j.mam.2011.10.008 REFERENCE PMID:26303601 AUTHORS McCoin CS, Knotts TA, Adams SH TITLE Acylcarnitines--old actors auditioning for new roles in metabolic physiology. JOURNAL Nat Rev Endocrinol 11:617-25 (2015) DOI:10.1038/nrendo.2015.129 REFERENCE PMID:28955734 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 Biochem Biophys Rep 10:32-38 (2017) DOI:10.1016/j.bbrep.2017.02.002 REL_PATHWAY ko00020 Citrate cycle (TCA cycle) ko00190 Oxidative phosphorylation ko04010 MAPK signaling pathway ko04022 cGMP-PKG signaling pathway ko04024 cAMP signaling pathway ko04150 mTOR signaling pathway ko04923 Regulation of lipolysis in adipocytes ///