PI3Ka-Akt1-mediated Prdm4 induction in adipose tissue increases energy expenditure, inhibits weight gain, and improves insulin resistance in diet-induced obese mice

Cell Death & Disease
No-Joon SongKye Won Park

Abstract

Stimulation of white adipose tissue (WAT) browning is considered as a potential approach to treat obesity and metabolic diseases. Our previous studies have shown that phytochemical butein can stimulate WAT browning through induction of Prdm4 in adipocytes. Here, we investigated the effects of butein on diet-induced obesity and its underlying molecular mechanism. Treatment with butein prevented weight gains and improved metabolic profiles in diet-induced obese mice. Butein treatment groups also displayed higher body temperature, increased energy expenditure, and enhanced expression of thermogenic genes in adipose tissue. Butein also suppressed body weight gains and improved glucose and insulin tolerance in mice housed at thermoneutrality (30 °C). These effects were associated with adipose-selective induction of Prdm4, suggesting the role of Prdm4 in butein-mediated anti-obese effects. To directly assess the in vivo role of Prdm4, we generated aP2-Prdm4 transgenic mouse lines overexpressing Prdm4 in adipose tissues. Adipose-specific transgenic expression of Prdm4 recapitulated the butein's actions in stimulating energy expenditure, cold tolerance, and thermogenic gene expression, resulting in prevention of obesity and improvement...Continue Reading

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Citations

May 17, 2019·Adipocyte·Bianca HemmeryckxIlse Scroyen
Mar 25, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Sandip MukherjeeAnutosh Chakraborty
Feb 27, 2021·Frontiers in Genetics·Xingyi ChenLinsen Zan

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Methods Mentioned

BETA
transgenic
PCR
fluorescence microscopy
electrophoresis
NMR

Software Mentioned

GraphPad Prism

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