Vitamin E tocotrienols improve insulin sensitivity through activating peroxisome proliferator-activated receptors.
Vitamin E is comprised of two classes of compounds: tocopherols and tocotrienols. Tocotrienol-enriched palm oil has been shown to help reduce blood glucose levels in patients and preclinical animal models. However, the mechanistic basis for tocotrienol action is not well established. Peroxisome proliferator-activated receptors alpha, gamma, and delta (PPARalpha, PPARgamma, and PPARdelta) are ligand-regulated transcription factors that play essential roles in energy metabolism. Importantly, synthetic PPARalpha and PPARgamma ligands are currently used for treating hyperlipidemia and diabetes. In this study, we present data that tocotrienols within palm oil functioned as PPAR modulators. Specifically, both alpha- and gamma-tocotrienol activated PPARalpha, while delta-tocotrienol activated PPARalpha, PPARgamma, and PPARdelta in reporter-based assays. Tocotrienols enhanced the interaction between the purified ligand-binding domain of PPARalpha with the receptor-interacting motif of coactivator PPARgamma coactivator-1alpha. In addition, the tocotrienol-rich fraction of palm oil improved whole body glucose utilization and insulin sensitivity of diabetic Db/Db mice by selectively regulating PPAR target genes. These lines of evidence collectively suggested that PPARs represent a set of molecular targets of tocotrienols.
Fang
Fang
F
Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Science City, Guangzhou, P. R. China.
Kang
Zhanfang
Z
Wong
Chiwai
C
D000818:Animals; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control; D019587:Dietary Supplements / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use*; D007333:Insulin Resistance; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D000073878:Palm Oil; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D008517:Phytotherapy; D010938:Plant Oils / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D054730:Protein Interaction Domains and Motifs / Q000235:genetics; D020033:Protein Isoforms / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D024508:Tocotrienols / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use*; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors; D000071247:Uncoupling Protein 3
D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D007473:Ion Channels; D024101:Mitochondrial Proteins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D047492:Peroxisome Proliferator-Activated Receptors; D010938:Plant Oils; C485290:Ppargc1a protein, mouse; D020033:Protein Isoforms; C495693:Slc2a4 protein, mouse; D024508:Tocotrienols; D015534:Trans-Activators; D014157:Transcription Factors; D000071247:Uncoupling Protein 3; D000073878:Palm Oil; D002334:Carnitine O-Palmitoyltransferase