KEGG   PATHWAY: map04714
Entry
map04714                    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
map04714  Thermogenesis
map04714

Other DBs
GO: 1990845
Reference
  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
  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
  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
  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
Mol Nutr Food Res 60:18-42 (2016)
DOI:10.1002/mnfr.201500251
Reference
  Authors
van Dam AD, Kooijman S, Schilperoort M, Rensen PC, Boon MR
  Title
Regulation of brown fat by AMP-activated protein kinase.
  Journal
Trends Mol Med 21:571-9 (2015)
DOI:10.1016/j.molmed.2015.07.003
Reference
  Authors
Kooijman S, van den Heuvel JK, Rensen PC
  Title
Neuronal Control of Brown Fat Activity.
  Journal
Trends Endocrinol Metab 26:657-68 (2015)
DOI:10.1016/j.tem.2015.09.008
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
Redox Biol 12:854-863 (2017)
DOI:10.1016/j.redox.2017.04.019
Reference
  Authors
Fruhbeck G, Mendez-Gimenez L, Fernandez-Formoso JA, Fernandez S, Rodriguez A
  Title
Regulation of adipocyte lipolysis.
  Journal
Nutr Res Rev 27:63-93 (2014)
DOI:10.1017/S095442241400002X
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
IUBMB Life 56:379-85 (2004)
DOI:10.1080/15216540400009968
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
Int J Obes (Lond) 34 Suppl 1:S28-33 (2010)
DOI:10.1038/ijo.2010.180
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
Mol Cell Biol 25:5466-79 (2005)
DOI:10.1128/MCB.25.13.5466-5479.2005
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
Nat Commun 7:11158 (2016)
DOI:10.1038/ncomms11158
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
Nat Commun 6:7052 (2015)
DOI:10.1038/ncomms8052
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
Mol Cell 57:235-46 (2015)
DOI:10.1016/j.molcel.2014.12.005
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
Cell Rep 15:2536-49 (2016)
DOI:10.1016/j.celrep.2016.05.019
Reference
  Authors
Villarroya F, Peyrou M, Giralt M
  Title
Transcriptional regulation of the uncoupling protein-1 gene.
  Journal
Biochimie 134:86-92 (2017)
DOI:10.1016/j.biochi.2016.09.017
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
Mol Cell Biol 24:3057-67 (2004)
DOI:10.1128/MCB.24.7.3057-3067.2004
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
J Biol Chem 286:12983-90 (2011)
DOI:10.1074/jbc.M110.215889
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
Cell Rep 20:641-654 (2017)
DOI:10.1016/j.celrep.2017.06.069
Reference
  Authors
Klingenberg M
  Title
UCP1 - A sophisticated energy valve.
  Journal
Biochimie 134:19-27 (2017)
DOI:10.1016/j.biochi.2016.10.012
Reference
  Authors
Bertholet AM, Kirichok Y
  Title
UCP1: A transporter for H(+) and fatty acid anions.
  Journal
Biochimie 134:28-34 (2017)
DOI:10.1016/j.biochi.2016.10.013
Reference
  Authors
Betz MJ, Enerback S
  Title
Targeting thermogenesis in brown fat and muscle to treat obesity and metabolic disease.
  Journal
Nat Rev Endocrinol 14:77-87 (2018)
DOI:10.1038/nrendo.2017.132
Reference
  Authors
Tseng YH, Cypess AM, Kahn CR
  Title
Cellular bioenergetics as a target for obesity therapy.
  Journal
Nat Rev Drug Discov 9:465-82 (2010)
DOI:10.1038/nrd3138
Reference
  Authors
Fenzl A, Kiefer FW
  Title
Brown adipose tissue and thermogenesis.
  Journal
Horm Mol Biol Clin Investig 19:25-37 (2014)
DOI:10.1515/hmbci-2014-0022
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
Cell Rep 17:29-36 (2016)
DOI:10.1016/j.celrep.2016.08.086
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
Genes Dev 26:271-81 (2012)
DOI:10.1101/gad.177857.111
Reference
  Authors
Zois NE, Bartels ED, Hunter I, Kousholt BS, Olsen LH, Goetze JP
  Title
Natriuretic peptides in cardiometabolic regulation and disease.
  Journal
Nat Rev Cardiol 11:403-12 (2014)
DOI:10.1038/nrcardio.2014.64
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
Mol Aspects Med 32:223-33 (2011)
DOI:10.1016/j.mam.2011.10.008
Reference
  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
  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
Related
pathway
map00020  Citrate cycle (TCA cycle)
map00190  Oxidative phosphorylation
map04010  MAPK signaling pathway
map04022  cGMP-PKG signaling pathway
map04024  cAMP signaling pathway
map04150  mTOR signaling pathway
map04923  Regulation of lipolysis in adipocytes
KO pathway
ko04714   
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