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Delayed treatment with fenofibrate protects against high-fat diet-induced kidney injury in mice: the possible role of AMPK autophagy

Title
Delayed treatment with fenofibrate protects against high-fat diet-induced kidney injury in mice: the possible role of AMPK autophagy
Authors
Sohn, MinjiKim, KeumjiUddin, Md JamalLee, GayoungHwang, InahKang, HyejiKim, HyunjiLee, Jung HwaHa, Hunjoo
Ewha Authors
하헌주
SCOPUS Author ID
하헌주scopus
Issue Date
2017
Journal Title
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
ISSN
1931-857XJCR Link1522-1466JCR Link
Citation
vol. 312, no. 2, pp. F323 - F334
Keywords
AMPKautophagyfenofibratehigh-fat dietkidney injury
Publisher
AMER PHYSIOLOGICAL SOC
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Fenofibrate activates not only peroxisome proliferator-activated receptor-alpha (PPAR alpha) but also adenosine monophosphate-activated protein kinase (AMPK). AMPK-mediated cellular responses protect kidney from high-fat diet (HFD)-induced injury, and autophagy resulting from AMPK activation has been regarded as a stress-response mechanism. Thus the present study examined the role of AMPK and autophagy in the renotherapeutic effects of fenofibrate. C57BL/6J mice were divided into three groups: normal diet (ND), HFD, and HFD + fenofibrate (HFD + FF). Fenofibrate was administered 4 wk after the initiation of the HFD when renal injury was initiated. Mouse proximal tubule cells (mProx24) were used to clarify the role of AMPK. Feeding mice with HFD for 12 wk induced insulin resistance and kidney injury such as albuminuria, glomerulosclerosis, tubular injury, and inflammation, which were effectively inhibited by fenofibrate. In addition, fenofibrate treatment resulted in the activation of renal AMPK, upregulation of fatty acid oxidation (FAO) enzymes and antioxidants, and induction of autophagy in the HFD mice. In mProx24 cells, fenofibrate activated AMPK in a concentration-dependent manner, upregulated FAO enzymes and antioxidants, and induced autophagy, all of which were inhibited by treatment of compound C, an AMPK inhibitor. Fenofibrate-induced autophagy was also significantly blocked by AMPK alpha 1 siRNA but not by PPAR alpha siRNA. Collectively, these results demonstrate that delayed treatment with fenofibrate has a therapeutic effect on HFD-induced kidney injury, at least in part, through the activation of AMPK and induction of subsequent downstream effectors: autophagy, FAO enzymes, and antioxidants.
DOI
10.1152/ajprenal.00596.2015
Appears in Collections:
약학대학 > 약학과 > Journal papers
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