Soy isoflavones improve the oxidative stress induced hypothalamic inflammation and apoptosis in high fat diet-induced obese male mice through PGC1-alpha pathway.

Dejiang Pang,Chengcheng Yang,Chao Li,Bin Feng,Zhengli Chen,Qihui Luo,Lixia Li,Chao Huang,Wentao Liu,Yuanfeng Zou

doi:10.18632/aging.103197

Dejiang Pang, Chengcheng Yang + Show 8 more

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https://doi.org/10.18632/aging.103197

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Abstract

Obesity is a common metabolic disorder that increases the risk of many diseases, such as type II diabetes, hypertension, cardiovascular disease. Hypothalamus plays a very important role in the progression of obesity, and many studies reveal that hypothalamic injures are implicated in obesity processes. Here, we describe that the consumption of soy isoflavones, with a structural similarity to that of estradiol, could mitigate obesity through improving the hypothalamic inflammation and apoptosis, which are induced by oxidative stress. Also, our in vitro studies demonstrate that daidzein and genistein, common ingredients of soy isoflavones, could protect hypothalamic N42 cells against palmitic acid induced oxidative stress and apoptosis. Moreover, the transcriptional coactivator peroxisome proliferator-activated receptor γ coactivator 1 alpha (PGC1-alpha), which plays a role in oxidative defense, is increased after soy isoflavone treatment in vivo and in vitro, suggesting an improved effect of soy isoflavones on hypothalamic antioxidant defense is mediated by PGC-1α. Our study reveals a potential mechanism of soy isoflavones regulating oxidative stress induced hypothalamic inflammation and cellular apoptosis, which will be important for obesity treatment.

Highlights

Obesity, as a serious public health problem, will greatly increase the risk of many diseases, such as type II diabetes, hypertension, cardiovascular disease, sleep apnea, psychological diseases and tumors [1,2,3,4]
After the consumption of SIF, we found that the high dose of soy isoflavones (HSIF) and the middle dose of soy isoflavones (MSIF) could significantly reduce the body weight of diet-induced obesity (DIO) male mice, but there was no statistical difference of body weight between the low dose of soy isoflavones group (LSIF) and the obesity control group (OB group) (Figure 1C)
We found a significant reduction of TG and low-density lipoproteins (LDL) concentrations in the soy isoflavones groups compared with those in the OB group, especially in MSIF and HSIF ones (Figure 1E, 1F)

Summary

Introduction

As a serious public health problem, will greatly increase the risk of many diseases, such as type II diabetes, hypertension, cardiovascular disease, sleep apnea, psychological diseases and tumors [1,2,3,4]. The occurrence of obesity is caused by the imbalance in the homeostasis of the maintenance of body fat volume, which is caused by many reasons, including genetic susceptibility and the influence of environmental factors [5]. Under the influence of this diet habit, the occurrence of obesity is with a high speed, and with a lower age [6]. It has very important scientific and clinical significance to carry www.aging-us.com out detailed and in-depth research on the mechanism of dietary induced obesity and to propose reasonable intervention and treatment methods on this basis. The study of Thaler et al shown that the onset of hypothalamic neuroinflammation was earlier than that of obesity, suggesting that hypothalamic neuroinflammation may be the key cause of obesity [10]

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