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Piperonal prevents high-fat diet-induced hepatic steatosis and insulin resistance in mice via activation of adiponectin/AMPK pathway

Abstract

Objective:

Piperonal is an important flavor additive with antibacterial and anxiolytic properties. We investigated the effects and possible mechanisms of piperonal protection against high-fat diet (HFD)-induced hepatic steatosis and insulin resistance.

Methods:

C57BL/6 J mice were fed with a normal diet (ND; based on the AIN-76 rodent diet), HFD (20% fat and 1% cholesterol), or piperonal-supplemented diet (POD; HFD supplemented with 0.05% piperonal) for 10 weeks.

Results:

Piperonal supplementation reduced hepatic lipid concentrations, liver dysfunction and plasma levels of insulin and glucose in HFD-fed mice. Piperonal significantly enhanced mRNA expression and secretion of adiponectin in 3T3-L1 adipocytes. Dietary piperonal significantly increased circulating adiponectin levels and hepatic AMP-activated protein kinase (AMPK) activation in HFD-fed mice; these were associated with the suppression of sterol regulatory element binding protein-1c and activation of glucose transporter-2 translocation in the livers. Piperonal also significantly reduced the expression of endoplasmic reticulum (ER) stress markers in the livers of HFD-fed mice.

Conclusions:

Piperonal may activate the adiponectin/AMPK pathway in the livers of mice. The activated adiponectin/AMPK axis may inhibit p70S6 kinase signaling and the ER stress response, with protective effects on hepatic steatosis and insulin resistance.

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Acknowledgements

This work was supported by the Industrialization Support Program for Biotechnology of Agriculture and Forestry (810002031SB110), Ministry for Food, Agriculture, Forestry and Fisheries, Republic of Korea and by the SRC program (Center for Food and Nutritional Genomics: no. 2012-0000643) of the National Research Foundation (NRF) of Korea funded by the Ministry of Education, Science and Technology.

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Correspondence to T Park.

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Li, X., Choi, Y., Yanakawa, Y. et al. Piperonal prevents high-fat diet-induced hepatic steatosis and insulin resistance in mice via activation of adiponectin/AMPK pathway. Int J Obes 38, 140–147 (2014). https://doi.org/10.1038/ijo.2013.70

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