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Animal Models

Dietary luteolin activates browning and thermogenesis in mice through an AMPK/PGC1α pathway-mediated mechanism

Abstract

Background:

Two brown-like adipocytes, including classical brown adipocytes from brown adipose tissues and beige cells from white adipose tissues, regulate thermogenesis. The developmental and functional induction of brown-like cells provides a defense against obesity and associated metabolic diseases. Our previous study suggests dietary luteolin can improve diet-induced obesity and insulin resistance in mice. Here we further elucidated the action of the natural flavonoid on energy expenditure and adaptive thermogenesis.

Methods:

Five-week-old male C57BL/6 mice were fed low-fat diet (LFD), high-fat diet (HFD) and HFD supplemented with 0.01% luteolin. After 12 weeks, their energy expenditure were detected using a combined indirect calorimetry system. Moreover, thermogenic program and associated molecular regulators were assessed in adipose tissues. In another independent study, even-aged mice were fed LFD and luteolin-containing LFD for 12 weeks, and their energy expenditure and thermogenic program were also investigated. Finally, differentiated primary brown and subcutaneous adipocytes were used to identify the critical participation of AMPK/PGC1α signaling in luteolin-regulated browning and thermogenesis.

Results:

In mice fed either HFD or LFD, dietary luteolin supplement increased oxygen consumption, carbon dioxide production and respiratory exchange ratio. The enhancement in energy expenditure was accompanied by the upregulation of thermogenic genes in brown and subcutaneous adipose tissues. Meanwhile, several important AMPK/PGC1α signaling molecules were activated by dietary luteolin in the tissues. Further, luteolin treatment directly elevated thermogenic gene expressions and activated AMPK/PGC1α signaling in differentiated primary brown and subcutaneous adipocytes, whereas AMPK inhibitor Compound C reversed the efficiencies.

Conclusions:

Dietary luteolin activated browning and thermogenesis through an AMPK/PGC1α pathway-mediated mechanism.

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Acknowledgements

This work was supported by projects from National Natural Science Foundation of China (Grant Numbers 311171315 and 31471320 to JL, and 31401204 to BB); The Fundamental Research Funds for the Central Universities, China (Grant Number 2014HGCH0005 to JL); Anhui Science and Technology Research Projects of China (Grant Number 1401b042018 to JL); and the Anhui Provincial Natural Science Foundation (Grant Number 1408085QC48 to BB).

Author contributions

XZ conceived and designed the experiments, performed the study and wrote the manuscript. Q-XZ, XW and LZ participated in the study and contributed to data analysis. WQ and BB contributed to data analysis and revised manuscript. JL reviewed/approved the research protocol, edited the manuscript and has taken full responsibility for the work as a whole, including the study design, access to data and the decision to submit and publish the manuscript.

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Correspondence to J Liu.

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The authors declare no conflict of interest.

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Supplementary Information accompanies this paper on International Journal of Obesity website

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Zhang, X., Zhang, QX., Wang, X. et al. Dietary luteolin activates browning and thermogenesis in mice through an AMPK/PGC1α pathway-mediated mechanism. Int J Obes 40, 1841–1849 (2016). https://doi.org/10.1038/ijo.2016.108

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