Wolfberries potentiate mitophagy and enhance mitochondrial biogenesis leading to prevention of hepatic steatosis in obese mice: the role of AMP-activated protein kinase α2 subunit.
METHODS
The aim of this study is to investigate whether AMP-activated protein kinase α2 (AMPKα2) is essential for wolfberry's protective effects on mitochondrial dysfunction and subsequent hepatic steatosis in mice.


RESULTS
Six-week-old male AMPKα2 knockout mice and genetic background C57BL/6J (B6) mice were fed a control, high-fat diet (HD, 45% (kilocalorie) fat), and/or HD with 5% (kilocalarie) wolfberry diets for 18 wk. At termination, blood and liver tissues were sampled for analysis by ELISA, HPLC, microscopy, real-time PCR, and Western blot. HD lowered hepatic lutein and zeaxanthin contents, inhibited protein expression of β,β-carotene 9',10'-oxygenase 2 (BCO2) and heat shock protein 60 in mitochondria, increased reactive oxygen species level, and 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 coactivator 1 α, resulting in hepatic steatosis in B6 and knockout mice. Dietary wolfberry elevated the xanthophyll concentrations and enhanced expression of BCO2 and heat shock protein 60, attenuated mitochondrial oxidative stress, activated AMPKα2, potentiated mitophagy and mitochondrial biogenesis, and enhanced lipid oxidation and secretion in the liver of B6 mice.


CONCLUSIONS
Dietary wolfberry selectively activated AMPKα2, which resulted in enhanced mitochondrial biogenesis and potentiated mitophagy, leading to the prevention of hepatic steatosis in obese mice.
Department of Nutritional Sciences, Oklahoma State University, Stillwater, OK, USA.
Dingbo
D
Lin
Hui
H
He
Hua
H
Ji
Jordan
J
Willis
Lloyd
L
Willard
Yu
Y
Jiang
Denis M
DM
Medeiros
Logan
L
Wark
Jing
J
Han
Yongzhang
Y
Liu
Bin
B
Lu
D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000071189:Autophagy-Related Protein-1 Homolog; D018834:Chaperonin 60 / Q000235:genetics / Q000378:metabolism; D059305:Diet, High-Fat; D049308:Dioxygenases / Q000235:genetics / Q000378:metabolism; D005234:Fatty Liver / Q000473:pathology / Q000517:prevention & control*; D005638:Fruit / Q000737:chemistry; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D014975:Lutein / Q000097:blood; D032305:Lycium / Q000737:chemistry*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008820:Mice, Obese; D008928:Mitochondria / Q000378:metabolism; D063306:Mitophagy / Q000502:physiology*; D018384:Oxidative Stress; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D024341:Xanthophylls / Q000097:blood
D018834:Chaperonin 60; D047495:PPAR gamma; D017382:Reactive Oxygen Species; D024341:Xanthophylls; D049308:Dioxygenases; C481678:Bco2 protein, mouse; C534978:Prkaa2 protein, mouse; D000071189:Autophagy-Related Protein-1 Homolog; D017346:Protein Serine-Threonine Kinases; C112444:Ulk1 protein, mouse; D055372:AMP-Activated Protein Kinases; D014975:Lutein
AMP-activated protein kinase α2; Hepatic steatosis; Mitochondrial biogenesis; Mitophagy; Wolfberry