Berberine protects against high fat diet-induced dysfunction in muscle mitochondria by inducing SIRT1-dependent mitochondrial biogenesis.
Berberine (BBR) has recently been shown to improve insulin sensitivity in rodent models of insulin resistance. Although this effect was explained partly through an observed activation of AMP-activated protein kinase (AMPK), the upstream and downstream mediators of this phenotype were not explored. Here, we show that BBR supplementation reverts mitochondrial dysfunction induced by High Fat Diet (HFD) and hyperglycemia in skeletal muscle, in part due to an increase in mitochondrial biogenesis. Furthermore, we observe that the prevention of mitochondrial dysfunction by BBR, the increase in mitochondrial biogenesis, as well as BBR-induced AMPK activation, are blocked in cells in which SIRT1 has been knocked-down. Taken together, these data reveal an important role for SIRT1 and mitochondrial biogenesis in the preventive effects of BBR on diet-induced insulin resistance.
Center for Neurosciences and Cell Biology, Department of Life Sciences, University of Coimbra 3004-517 Coimbra, Portugal.
Ana P
AP
Gomes
Filipe V
FV
Duarte
Patricia
P
Nunes
Basil P
BP
Hubbard
João S
JS
Teodoro
Ana T
AT
Varela
John G
JG
Jones
David A
DA
Sinclair
Carlos M
CM
Palmeira
Anabela P
AP
Rolo
D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D001599:Berberine / Q000494:pharmacology*; D002460:Cell Line; D059305:Diet, High-Fat; D005947:Glucose / Q000378:metabolism; D006728:Hormones / Q000378:metabolism; D006943:Hyperglycemia / Q000378:metabolism; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D008931:Mitochondria, Muscle / Q000187:drug effects* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D032446:Myoblasts / Q000187:drug effects / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D009765:Obesity / Q000378:metabolism; D001678:Organelle Biogenesis; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*
D006728:Hormones; D001599:Berberine; D009243:NAD; D055372:AMP-Activated Protein Kinases; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; D005947:Glucose