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Wolfberries potentiate mitophagy in the liver of obese mice (372.3)
Author(s) -
Lin Dingbo,
Medeiros Denis
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.372.3
Subject(s) - mitophagy , ampk , steatosis , endocrinology , amp activated protein kinase , medicine , mitochondrial biogenesis , pink1 , oxidative stress , mitochondrion , fatty liver , reactive oxygen species , chemistry , biology , protein kinase a , kinase , biochemistry , autophagy , apoptosis , disease
Objective: The aim is to investigate whether AMP‐activated protein kinase α2 (AMPKα2) is essential for wolfberry protective effects on mitochondrial dysfunction and subsequent hepatic steatosis in mice.Methods: Six‐week‐old male AMPKα2 knockout (KO) mice and genetic background C57BL/6J (B6) mice were fed the control, high‐fat (HD, 45% [kcal] fat), and/or HD with 5% (kcal) wolfberry diets for 18 weeks. At termination, blood and liver tissues were sampled for analysis by ELISA, HPLC, microscopy, real‐time PCR, and Western blot. Results: HD lowered hepatic lutein and zeaxanthin contents, inhibited β,β‐carotene 9,10 oxygenase 2 (BCO2) protein expression, induced mitochondrial oxidative stress as indicated by an increased reactive oxygen species level and the decreased mitochondrial membrane potential, respiratory rate, and aconitase activity. HD also suppressed mitophagy and mitochondrial biogenesis as determined by accumulation of p62, inhibited phosphorylation of Unc‐51‐like kinase 1 on Ser555, and declined expression of peroxisome proliferator‐activated receptor γ co‐activator 1 α, resulting in hepatic steatosis in B6 and KO mice. Dietary wolfberry elevated the xanthophyll concentrations and enhanced BCO2 expression, attenuated mitochondrial oxidative stress, activated AMPKα2, potentiated mitophagy and mitochondrial biogenesis, and enhanced lipid oxidation and secretion in the liver of B6 mice. Conclusion: Dietary wolfberry selectively activated AMPKα2, which resulted in enhanced mitochondrial biogenesis and potentiated mitophagy, leading to the prevention of hepatic steatosis in obese mice. Grant Funding Source : Supported by NIH NCRR Grant P20‐RR‐017686