PMID- 30848932
OWN - NLM
STAT- MEDLINE
DCOM- 20200518
LR  - 20200518
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 33
IP  - 6
DP  - 2019 Jun
TI  - Berberine alleviates nonalcoholic fatty liver induced by a high-fat diet in mice 
      by activating SIRT3.
PG  - 7289-7300
LID - 10.1096/fj.201802316R [doi]
AB  - Berberine (BBR) shows promising effects in the treatment of nonalcoholic fatty 
      liver disease (NAFLD) by influencing various metabolic aspects. Inhibition of 
      mitochondrial beta-oxidation (beta-OX) participates in the pathogenesis of NAFLD. 
      Silent mating-type information regulation 2 homolog 3 (SIRT3) has been reported 
      to regulate mitochondrial beta-OX by deacetylating its substrate, long-chain 
      acyl-coenzyme A dehydrogenase (LCAD). This study aimed to explore whether BBR can 
      promote mitochondrial beta-OX and the role of SIRT3 as well as the mechanisms 
      underlying the effects of BBR on hepatic lipid metabolism in mice fed a high-fat 
      diet (HFD). BBR can significantly improve systematic and hepatic lipid metabolism 
      in HFD-fed mice. Metabolomics analysis revealed that beta-OX was inhibited in 
      HFD-induced mice, as indicated by the reduced production of short and medium 
      carbon chain acyl-carnitines, the activated form of free fatty acids, via beta-OX, 
      which was reversed by BBR intervention. Exploration of the mechanism found that 
      BBR intervention reversed the down-regulation of SIRT3 and decreased the LCAD 
      hyperacetylation level in HFD-fed mice. SIRT3 knockout (KO) mice were used to 
      identify the role of SIRT3 in the BBR's influence of beta-OX. The beneficial effects 
      of BBR on systemic and hepatic metabolism were profoundly attenuated in KO mice. 
      Moreover, the promotive effect of BBR on beta-OX in HFD-induced mice was partially 
      abolished in KO mice. These results suggested that BBR alleviates HFD-induced 
      inhibition of fatty acid beta-OX partly through SIRT3-mediated LCAD deacetylation, 
      which may provide a novel mechanism and support BBR as a promising therapeutic 
      for NAFLD.-Xu, X., Zhu, X.-P., Bai, J.-Y., Xia, P., Li, Y., Lu, Y., Li, X.-Y., 
      Gao, X. Berberine alleviates nonalcoholic fatty liver induced by a high-fat diet 
      in mice by activating SIRT3.
FAU - Xu, Xi
AU  - Xu X
AD  - Department of Endocrinology and Metabolism, Affiliated Zhongshan Hospital of 
      Fudan University, Shanghai, China.
FAU - Zhu, Xiao-Peng
AU  - Zhu XP
AD  - Department of Endocrinology and Metabolism, Affiliated Zhongshan Hospital of 
      Fudan University, Shanghai, China.
FAU - Bai, Jin-Yun
AU  - Bai JY
AD  - Department of Endocrinology and Metabolism, Affiliated Zhongshan Hospital of 
      Fudan University, Shanghai, China.
FAU - Xia, Pu
AU  - Xia P
AD  - Department of Endocrinology and Metabolism, Affiliated Zhongshan Hospital of 
      Fudan University, Shanghai, China.
AD  - Fudan Institute for Metabolic Diseases, Shanghai, China; and.
FAU - Li, Yu
AU  - Li Y
AD  - Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, 
      Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 
      University of Chinese Academy of Sciences, Shanghai, China.
FAU - Lu, Yan
AU  - Lu Y
AD  - Department of Endocrinology and Metabolism, Affiliated Zhongshan Hospital of 
      Fudan University, Shanghai, China.
AD  - Fudan Institute for Metabolic Diseases, Shanghai, China; and.
FAU - Li, Xiao-Ying
AU  - Li XY
AD  - Department of Endocrinology and Metabolism, Affiliated Zhongshan Hospital of 
      Fudan University, Shanghai, China.
AD  - Fudan Institute for Metabolic Diseases, Shanghai, China; and.
FAU - Gao, Xin
AU  - Gao X
AD  - Department of Endocrinology and Metabolism, Affiliated Zhongshan Hospital of 
      Fudan University, Shanghai, China.
AD  - Fudan Institute for Metabolic Diseases, Shanghai, China; and.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190308
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (Fatty Acids)
RN  - 0 (Sirt3 protein, mouse)
RN  - 0 (acylcarnitine)
RN  - 0I8Y3P32UF (Berberine)
RN  - EC 1.3.8.8 (Acyl-CoA Dehydrogenase, Long-Chain)
RN  - EC 3.5.1.- (Sirtuin 3)
RN  - IY9XDZ35W2 (Glucose)
RN  - S7UI8SM58A (Carnitine)
SB  - IM
MH  - Acetylation
MH  - Acyl-CoA Dehydrogenase, Long-Chain/metabolism
MH  - Animals
MH  - Berberine/*pharmacology/therapeutic use
MH  - Carnitine/analogs & derivatives/metabolism
MH  - Diet, High-Fat/*adverse effects
MH  - Drug Evaluation, Preclinical
MH  - Enzyme Activation/drug effects
MH  - Fatty Acids/metabolism
MH  - Glucose/metabolism
MH  - Insulin Resistance
MH  - Lipid Metabolism/drug effects
MH  - Male
MH  - Metabolome/*drug effects
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mitochondria, Liver/*drug effects/enzymology
MH  - Non-alcoholic Fatty Liver Disease/*drug therapy/enzymology/etiology/pathology
MH  - Obesity/complications
MH  - Oxidation-Reduction
MH  - Protein Processing, Post-Translational
MH  - Sirtuin 3/deficiency/*drug effects/physiology
OTO - NOTNLM
OT  - BBR
OT  - LCAD
OT  - mitochondrial beta-OX
EDAT- 2019/03/09 06:00
MHDA- 2020/05/19 06:00
CRDT- 2019/03/09 06:00
PHST- 2019/03/09 06:00 [pubmed]
PHST- 2020/05/19 06:00 [medline]
PHST- 2019/03/09 06:00 [entrez]
AID - 10.1096/fj.201802316R [doi]
PST - ppublish
SO  - FASEB J. 2019 Jun;33(6):7289-7300. doi: 10.1096/fj.201802316R. Epub 2019 Mar 8.