SCFA and skeletal muscle substrate metabolism (Homo sapiens)

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1Lipid storageGastrointestinal tractGPR43ButyrateAcetateGLP-1FA oxidationPPARDGPR41AMPK activationPropionatePYYGLUT4Insulin actionPlasma Fatty AcidsLipolysisGlycolysisGlycogen synthesisGPR41GPR43PropionateAcetate


The short-chain fatty acids (SCFA) acetate, propionate and butyrate can alter skeletal muscle metabolism both via direct and indirect mechanisms. Indirect mechanisms include the stimulation of glucagon like peptide 1 (GLP-1) and peptide YY (PYY) release via G-protein coupled receptor 41 (GPR41) and GPR43 signalling. Increased peripheral levels of these gut-derived satiety hormones induce the recruitment of microvasculature in skeletal muscle tissue and thereby contribute to improved insulin signalling. Furthermore SCFA induce a reduction in lipolysis in white adipose tissue (WAT), resulting in enhanced WAT lipid buffering capacity and decreased levels ectopic fat accumulation in skeletal muscle tissue.

SCFA are also suggested to have direct effects on skeletal muscle metabolism, possibly via GPR41 and GPR43 signalling. SCFA induce the activation of adenosine monophosphate-activated protein kinase (AMPK), a key regulator in skeletal muscle cell metabolism. Activated AMPK induces several metabolic pathways including fatty acid oxidation and the synthesis of glycogen. Active AMPK also stimulates glucose uptake via translocation of glucose transporter type 4 (GLUT4) and decreases glycolysis. In addition to AMPK activation, SCFA might also induce peroxisome proliferator activated receptor delta (PPARD) expression, another process contributing to enhanced fat oxidation levels.

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  1. Canfora EE, Jocken JW, Blaak EE; ''Short-chain fatty acids in control of body weight and insulin sensitivity''; Nat Rev Endocrinol., 2015 PubMed Europe PMC Scholia


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93221view16:41, 4 August 2017I6095275Modified description
93215view12:41, 4 August 2017DeSlChanged secondary chebi ID for plasma FA to primary.
93183view13:01, 2 August 2017Marvin M2Reverted to version '12:33, 2 August 2017' by Marvin M2
93181view12:34, 2 August 2017Marvin M2Ontology Term : 'muscle cell' added !
93180view12:33, 2 August 2017Marvin M2Ontology Term : 'altered energy metabolic pathway' added !
93165view19:41, 1 August 2017Marvin M2Improved lower GPR
93160view19:01, 1 August 2017MaintBotModified title
93159view17:24, 1 August 2017I6095275New pathway

External references


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NameTypeDatabase referenceComment
AMPK activationPathwayWP1403 (WikiPathways)
AcetateMetaboliteCHEBI:30089 (ChEBI)
ButyrateMetaboliteCHEBI:17968 (ChEBI)
FA oxidationPathwayWP143 (WikiPathways)
GLP-1GeneProductENSG00000115263 (Ensembl)
GLUT4GeneProductENSG00000181856 (Ensembl)
GPR41GeneProductENSG00000185897 (Ensembl)
GPR43GeneProductENSG00000126262 (Ensembl)
Glycogen synthesisPathwayWP500 (WikiPathways)
GlycolysisPathwayWP534 (WikiPathways)
Insulin actionPathwayWP481 (WikiPathways)
LipolysisPathwayWP3965 (WikiPathways)
PPARDGeneProductENSG00000112033 (Ensembl)
PYYGeneProductENSG00000131096 (Ensembl)
Plasma Fatty AcidsMetaboliteCHEBI:35366 (ChEBI)
PropionateMetaboliteCHEBI:17272 (ChEBI)

Annotated Interactions

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