Berberine reverts hepatic mitochondrial dysfunction in high-fat fed rats: a possible role for SirT3 activation

Mitochondrion. 2013 Nov;13(6):637-46. doi: 10.1016/j.mito.2013.09.002. Epub 2013 Sep 14.

Abstract

Berberine is an isoquinoline alkaloid with anti-diabetic properties. Despite the central role of liver and thus hepatic mitochondria in whole-body metabolism, berberine effects on hepatic mitochondrial function in an obesity model are still unknown. Here, we demonstrate that berberine treatment recovers mitochondrial efficiency when altered by a high-fat feeding. Mitochondria isolated from the liver of high-fat fed rats exhibited decreased capacity to accumulate calcium and impaired oxidative phosphorylation (OXPHOS) capacity, as shown by impaired mitochondrial membrane potential, oxygen consumption and cellular ATP levels. Interestingly, the recovery of mitochondrial function by berberine was associated with an increased activity of the mitochondrial sirtuin 3 (SirT3). In conclusion, berberine potent protective effects against metabolic syndrome may rely on increasing mitochondrial SirT3 activity, normalizing mitochondrial function and preventing a state of energetic deficit caused by impaired OXPHOS.

Keywords: ACC; AMP-activated protein kinase; AMPK; BBR; Berberine; Ctl; FAME; FCCP; FFA; HFD; Liver bioenergetics; Mitochondrial function; NAFLD; OXPHOS; Obesity; RCR; ROS; Respiratory Control Ratio; SirT3; T2D; TPP+; acetyl-CoA carboxylase; berberine-supplemented HFD group; carbonylcyanide-P-trifluoromethoxyphenylhydrazon; control low fat diet-fed group; fatty acid methyl ester; free fatty acids; high fat diet-fed group; non-alcoholic fatty liver disease; oxidative phosphorylation; reactive oxygen species; sirtuin 3; tetraphenylphosphonium; type II diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Base Sequence
  • Berberine / administration & dosage
  • Berberine / pharmacology*
  • DNA Primers
  • Diet, High-Fat*
  • Membrane Potential, Mitochondrial
  • Mitochondria, Liver / drug effects*
  • Mitochondria, Liver / metabolism
  • Mitochondria, Liver / physiology
  • Oxidative Phosphorylation
  • Rats
  • Reactive Oxygen Species / metabolism
  • Real-Time Polymerase Chain Reaction
  • Sirtuin 3 / genetics
  • Sirtuin 3 / metabolism*

Substances

  • DNA Primers
  • Reactive Oxygen Species
  • Berberine
  • Adenosine Triphosphate
  • Sirtuin 3