Protective effects of Allium macrostemon extract on adipose tissue and liver dysregulation induced by high-fat diet and bisphenol A in C57BL/6 mice

Abstract

Abstract Exposure of humans to high-fat (HF) diet and bisphenol A (BPA) has increased in recent times, and co-exposure to these causes harmful tissue toxicity. Here, the preventive effect of Allium macrostemon (AM) extract against dysfunction of adipose tissue and the liver under co-exposure to BPA and HF diet was examined. C57BL/6 mice were fed control (CON) diet, HF diet, HF diet with an oral injection of BPA (HF + BP), or HF diet with an oral co-injection of BPA and AM extract (HF + BP + AM). While HF feeding increased body weight gain compared to CON feeding, BP + HF suppressed body weight gain. BP + HF with lower body weight than HF had similar epididymal fat mass and inflammatory stress as HF, but significantly higher serum triglyceride and free fatty acid levels. In the liver, altered endoplasmic reticulum (ER) stress response and decreased autophagy were observed in HF + BP, as shown by increased t-IRE1α, p-JNK, and p62 levels and decreased beclin-1 protein levels, compared to those in HF. HF + BP + AM reduced HF and BPA-induced pro-inflammatory responses in adipose tissue, ER stress in liver, and total cholesterol level in serum. In addition, ecdysterone 25-O-β-D-glucopyranoside and 6-gingerol were firstly identified in AM extract by mass spectrometry and molecular networking analysis. In summary, the AM extract diminished liver and adipose tissue dysregulation, including hepatic ER stress and adipose tissue inflammation while a HF diet and BPA co-exposure induced harmful health outcomes in adipocytes and the liver. Therefore, AM has the potential to alleviate the harmful effects of a HF diet and BPA via anti-ER stress and anti-inflammatory activities.