title: Genistein stimulates fatty acid oxidation in a leptin receptor-independent manner through the JAK2-mediated phosphorylation and activation of AMPK in skeletal muscle.
abstract: Obesity is a public health problem that contributes to the development of insulin resistance, which is associated with an excessive accumulation of lipids in skeletal muscle tissue. There is evidence that soy protein can decrease the ectopic accumulation of lipids and improves insulin sensitivity; however, it is unknown whether soy isoflavones, particularly genistein, can stimulate fatty acid oxidation in the skeletal muscle. Thus, we studied the mechanism by which genistein stimulates fatty acid oxidation in the skeletal muscle. We showed that genistein induced the expression of genes of fatty acid oxidation in the skeletal muscle of Zucker fa/fa rats and in leptin receptor (ObR)-silenced C2C12 myotubes through AMPK phosphorylation. Furthermore, the genistein-mediated AMPK phosphorylation occurred via JAK2, which was possibly activated through a mechanism that involved cAMP. Additionally, the genistein-mediated induction of fatty acid oxidation genes involved PGC1α and PPARδ. As a result, we observed that genistein increased fatty acid oxidation in both the control and silenced C2C12 myotubes, as well as a decrease in the RER in mice, suggesting that genistein can be used in strategies to decrease lipid accumulation in the skeletal muscle.
authors.affiliation: Posgrado Ciencias Bioquímicas, Facultad de Química, UNAM, México, D.F. 04510, Mexico; Departamento de Fisiología de la Nutrición, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México, D.F. 14000, Mexico.
authors.forename: Berenice
authors.initials: B
authors.lastname: Palacios-González
authors.forename: Angel
authors.initials: A
authors.lastname: Zarain-Herzberg
authors.forename: Isabel
authors.initials: I
authors.lastname: Flores-Galicia
authors.forename: Lilia G
authors.initials: LG
authors.lastname: Noriega
authors.forename: Gabriela
authors.initials: G
authors.lastname: Alemán-Escondrillas
authors.forename: Teresa
authors.initials: T
authors.lastname: Zariñan
authors.forename: Alfredo
authors.initials: A
authors.lastname: Ulloa-Aguirre
authors.forename: Nimbe
authors.initials: N
authors.lastname: Torres
authors.forename: Armando R
authors.initials: AR
authors.lastname: Tovar
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects / Q000235:genetics; D005227:Fatty Acids / Q000235:genetics / Q000378:metabolism*; D019833:Genistein / Q000494:pharmacology*; D053614:Janus Kinase 2 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D032448:Myoblasts, Skeletal / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D011924:Rats, Zucker; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D054411:Receptors, Leptin / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D016588:Anticarcinogenic Agents; D005227:Fatty Acids; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C091778:Ppard protein, mouse; C485290:Ppargc1a protein, mouse; C501429:Ppargc1a protein, rat; D018160:Receptors, Cytoplasmic and Nuclear; D054411:Receptors, Leptin; D014157:Transcription Factors; D019833:Genistein; C507926:Jak2 protein, mouse; C507927:Jak2 protein, rat; D053614:Janus Kinase 2; D055372:AMP-Activated Protein Kinases
keywords: 007; 5-amino 4-imidazolecarboxamide ribose; 5′-adenosine monophosphate-activated protein kinase; 8-(4-chlorophenylthio)-2-Omethyladenosine-3,5-cAMP; ACC; AICAR; AMPK; CAMKKβ; CPT1; Ca(2+)/calmodulin-dependent protein kinase kinase β; Epac1; FAO; FFA; Fatty acid oxidation; Genistein; HF; JAK2; Janus kinase 2; LEPR; ObR; PDE4; PLC; PPARα; PPARδ; SCD; SIRT1; SP; SREBP1c; Skeletal muscle; Soy protein; UCP3; acetyl CoA carboxylase; cAMP-regulated guanine nucleotide exchange factor; carnitine palmitoyl transferase-1; fatty acid oxidation; free fatty acids; high fat; leptin receptor; peroxisome proliferator activated receptor-δ PGC-1α, PPAR-γ coactivator-1α; peroxisome proliferator-activated receptor-α; phosphodiesterases; phospholipase C; sirtuin 1; soy protein; stearoyl-CoA desaturase-1; sterol regulatory element binding protein-1c; uncoupling carrier protein 3