Combined Exposure to Fructose and Bisphenol A Exacerbates Abnormal Lipid Metabolism in Liver of Developmental Male Rats

Abstract

The aim of this study was to investigate whether combined exposure to fructose and bisphenol A (BPA) has a synergistic effect on abnormal lipid metabolism in the liver of developmental male rats and its possible mechanism. Fifty weaned male Wistar rats were divided into five groups: the control, 13% fructose, 20% fructose, 1 µg/mL BPA, and 13% fructose + 1 µg/mL BPA (combined exposure). Rats were exposed to fructose and/or BPA through drinking water for eight weeks. Genes or proteins regulating lipid metabolism include sterol regulatory element binding protein 1 (SREBP1), adipose triglyceride lipase (ATGL), hormone sensitive lipase (HSL), acetyl-CoA carboxylase 1 (ACC1), fatty acid synthase (FAS), zinc α 2 glycoprotein (ZAG) and estrogen receptor α (ERα), and the expression of proteins regulating inflammatory response, such as TLR4 and NF-κB, were determined. Serum total cholesterol (T-CHO), triglyceride (TG), low, high density lipoprotein cholesterol (LDL-C, HDL-C), blood glucose, insulin, IL-17 and TNF-α levels were also measured. Liver tissue morphology was observed by H&E staining. The results showed that the levels of gene and protein catalyzing lipogenesis were increased (SREBP1, ACC1 and FAS), while those catalyzing lipolysis were decreased (ATGL, HSL and ZAG), accompanied by dyslipidemia, insulin resistance and hepatic fat accumulation, and there were higher expression of TLR4 and NF-κB protein and lower expression of ERα protein in liver, and increased serum IL-17 and TNF-α levels in fructose and/or BPA exposed rats compared with controls. Moreover, the above indicators were more serious in combined exposure group than in single exposure group. Therefore, abnormal lipid metabolism in the liver of developmental rats could be exacerbated by combined exposed to fructose and BPA.

Effects of Nigella sativa oil and thymoquinone against bisphenol A‐induced metabolic disorder in rats

“…In general, the liver plays a vital role in the metabolism of fat, synthesis, transport, and homeostasis of lipids and cholesterol. Liver dysfunction causes abnormal serum lipid profiles and triggers insulin resistance disorder (Lin et al, 2019).…”

Chronic high dietary sucrose induces sexually dimorphic metabolic adaptations in liver and adipose tissue

“…Reductions in estrogen signaling in response to sucrose intake would be expected to increase hepatic de novo fatty acid synthesis via upregulation of Fasn and Acaca (Qiu et al, 2017). In support of this notion, liquid fructose ingestion (13% w/v) has been shown to cause a reduction in hepatic ERa protein expression concomitant with increases in Fasn, Acaca, and steatosis (Lin et al, 2019), whereas de novo fatty acid synthesis induced by sucrose, fructose or glucose has been shown to reduce the hepatocyte-produced sex hormone binding globulin (SHBG) (Selva et al, 2007). SHBG is thought to interact with ERa to regulate the transport of estrogens (and testosterone) into tissues (Hammond, 2016), and it's concentrations are negatively associated with the severity of NAFLD and other metabolic disease risk-factors in humans (Kavanagh et al, 2013;Luo et al, 2018).…”

Bisphenol A (BPA) Leading to Obesity and Cardiovascular Complications: A Compilation of Current In Vivo Study

“…Meanwhile, decreased level of fatty acid amide hydrolase was able to enhance the system signaling of endocannabinoids, thus triggering the frequency of hunger [ 53 ]. Apart from this, the decrease of zinc α 2 glycoprotein (ZAG), hormone-sensitive lipase (HSL), and elevation of TLR4 and NF-κB are some other indications of BPA interference with lipid profile [ 24 ]. ZAG protein plays an important role in the mobilization of adipose tissue, thereby modulating lipid metabolism to maintain body weight.…”

“…ZAG protein plays an important role in the mobilization of adipose tissue, thereby modulating lipid metabolism to maintain body weight. Reduced ZAG levels, on the other hand, are linked to lipogenesis activation and lipolysis inhibition, as well as hepatic fat storage and dyslipidemia [ 24 ].…”