title: trans-Cinnamaldehyde stimulates mitochondrial biogenesis through PGC-1α and PPARβ/δ leading to enhanced GLUT4 expression.
abstract: Type 2 diabetes is characterized by insulin resistance and chronic hyperglycemia, and is increasing in incidence and severity. This work explored the effects of trans-cinnamaldehyde (CA) on carbohydrate metabolism, mitochondrial content, and related metabolic gene and protein expression in cultured myotubes treated with various concentrations of CA for up to 24 h. CA treatment increased myotube myocyte enhancer factor 2 (MEF2) along with glucose transporter 4 (GLUT4) content. CA treatment also significantly increased expression of markers of improved oxidative metabolism including 5' adenosine monophosphate-activated protein kinase (AMPK), peroxisome proliferator-activated receptor γ coactivator 1 α (PGC-1α), cytochrome c (CytC), as well as peroxisome proliferator-activated receptor α (PPARα) and PPARβ/δ. Despite increased expression of proteins associated with improved oxidative metabolism and glucose uptake, CA-treated myotubes exhibited significantly reduced oxidative metabolism compared with controlled cells. Additionally, CA treatment increased markers of glucose-mediated lipid biosynthesis without elevated PPARγ and sterol receptor element binding protein 1c (SREBP-1c) expression. The ability of CA to stimulate mitochondrial biogenesis and GLUT4 expression suggests CA may offer possible benefits for metabolic disease. However, increases in markers of fatty acid synthesis with simultaneously reduced oxidative metabolism suggest CA may have counterproductive effects for metabolic disease, warranting a need for further investigation.
authors.affiliation: School of Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA; Department of Biochemistry and Molecular Biology, University of New Mexico, Health Sciences Center, School of Medicine, Albuquerque, NM 87131, USA. Electronic address: ngannon@mcw.edu.
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Gannon
authors.affiliation: Department of Exercise Science, High Point University, High Point, NC 27268, USA. Electronic address: schnuj12@highpoint.edu.
authors.forename: Jamie K
authors.initials: JK
authors.lastname: Schnuck
authors.affiliation: Department of Health, Exercise and Sports Science, University of New Mexico, Albuquerque, NM 87131, USA. Electronic address: cmermier@unm.edu.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Mermier
authors.affiliation: Department of Individual, Family, and Community Education: Nutrition, University of New Mexico, Albuquerque, NM 87131, USA. Electronic address: cconn@unm.edu.
authors.forename: Carole A
authors.initials: CA
authors.lastname: Conn
authors.affiliation: Department of Exercise Science, High Point University, High Point, NC 27268, USA. Electronic address: rvaughan@highpoint.edu.
authors.forename: Roger A
authors.initials: RA
authors.lastname: Vaughan
mesh_terms: D000171:Acrolein / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival; D005421:Flavoring Agents / Q000009:adverse effects / Q000378:metabolism*; D005786:Gene Expression Regulation; D051275:Glucose Transporter Type 4 / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000378:metabolism*; D050356:Lipid Metabolism; D064326:MEF2 Transcription Factors / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008931:Mitochondria, Muscle / Q000201:enzymology / Q000378:metabolism; D063154:Mitochondrial Dynamics; D018485:Muscle Fibers, Skeletal / Q000201:enzymology / Q000378:metabolism*; D001678:Organelle Biogenesis; D010084:Oxidation-Reduction; D047494:PPAR delta / Q000819:agonists / Q000378:metabolism; D048068:PPAR-beta / Q000819:agonists / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000819:agonists* / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D005421:Flavoring Agents; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D064326:MEF2 Transcription Factors; D047494:PPAR delta; D048068:PPAR-beta; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; C495693:Slc2a4 protein, mouse; D000171:Acrolein; C012843:cinnamaldehyde
keywords: Glucose transporter 4 (GLUT4); Mitochondrial biogenesis; Oxidative metabolism; Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α); Type II diabetes mellitus