High-fat diet (HFD) and inflammation are the key
contributors to insulin resistance and type 2 diabetes (T2D). Previous study
shows fatty acid-induced accumulation of damaged, reactive oxygen species
(ROS)-generating mitochondria, and this in turn activates the NLRP3 inflammasome
interference with insulin signaling. Our previous research shows NLRP3
inflammasome activation signal originates from defects in autophagy. Yet how the
fatty acid related to mitophagy alteration leads to the activation of NLRP3-ASC
inflammasome has not been considered. Here we demonstrated that palmitate (PA)
induced mitophagy deficiency, leading to damaged mitochondrion as characterized
by mito-ROS production and loss of membrane potential. Antioxidant APDC or
Ca2+ signaling inhibitor Nifedipine blocked PA-induced
NLRP3 inflammasome activation. Further, we provided evidences that PA reduced
the expression of Ras homolog enriched in brain (Rheb) and disrupted Rheb
recruitment to the mitochondrial outer membrane. In addition, sustained PA
caused disassociation of kinesin family member 5B (KIF5B) from binding with
mitochondria via Ca2+-dependent effects. Disruption of Rheb and
KIF5B interaction with mitochondria blocked mitochondrial degradation along with
IL-1β dependent insulin resistance, which was majorly attenuated by Rheb/KIF5B
overexpression. In a consequence, defective mitophagy led to the accumulation of
damaged-ROS-generating mitochondria, down pathway of NLRP3-ASC-Caspase 1
activation, and subsequently, insulin resistance. These findings provide
insights into the association of inflammation, mitophagy and
T2D.
Objective : To investigate effects of hydrogen-rich water (HRW) on oxidative stress, liver function and HBV DNA in patients with chronic hepatitis B (CHB). Methods : Sixty patients with CHB were randomly assigned into routine treatment group or hydrogen treatment group in which patients received routine treatment alone or additional oral HRW (1200-1800 mL/day, twice daily), respectively, for 6 consecutive weeks. Serum oxidative stress, liver function, and HBV DNA level were detected before and after treatment. Thirty healthy subjects served as controls.Results : When compared with controls, oxidative stress was obvious in CHB patients, and the liver function also signifi cantly impaired. After treatment, the oxidative stress remained unchanged in routine treatment group, but markedly improved in hydrogen treatment group. The liver function was improved signifi cantly and the HBV DNA reduced markedly after corresponding treatments. Although a signifi cant difference was noted in the oxidative stress between two groups after treatment, the liver function and HBV DNA level were comparable after treatment and both had improved tendencies. Conclusion : HRW signifi cantly attenuates oxidative stress in CHB patients, but further study with long-term treatment is required to confi rm the effect of HRW on liver function and HBV DNA level. Clin Trans Sci 2013; Volume 6: 372-375
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