Berberine protects against high fat diet-induced dysfunction in muscle mitochondria by inducing SIRT1-dependent mitochondrial biogenesis

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1822

Article

Gomes, Ana P.^1,2  Duarte, Filipe V.¹  Nunes, Patricia¹  Hubbard, Basil P.²  Teodoro, Joao S.¹  Varela, Ana T.¹  Jones, John G.¹  Sinclair, David A.²  Palmeira, Carlos M.^1,3  Rolo, Anabela P.^1,4 

[1] Univ Coimbra, Dept Life Sci, Ctr Neurosci & Cell Biol, P-3004517 Coimbra, Portugal

[2] Harvard Univ, Sch Med, Dept Pathol Genet, Paul F Glen Labs Biol Mech Aging, Boston, MA 02115 USA

[3] Univ Coimbra, Fac Sci & Technol, Dept Life Sci, P-3004517 Coimbra, Portugal

[4] Univ Aveiro, Dept Biol, P-3810193 Aveiro, Portugal

关键词: Metabolic syndrome;    Berberine;    Mitochondria;    SIRT1;    AMPK;    NAMPT;   

DOI  :  10.1016/j.bbadis.2011.10.008

来源: Elsevier

【 摘 要 】

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. (C) 2011 Elsevier B.V. All rights reserved.

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