Perfluorooctanoic acid-induced lipid metabolism disorder in SD rat liver and its effect on the expression of fatty acid metabolism-related proteins.
10.11817/j.issn.1672-7347.2022.210320
- Author:
Li WANG
1
;
Yongbing ZHOU
2
;
Xinzhuang MA
2
;
Weiqiang SUN
3
;
Hui LIU
4
Author Information
1. Department of Nutrition and Food Hygiene, School of Public Health, Bengbu Medical College, Bengbu 233030. wangli@bbmc.edu.cn.
2. Department of Nutrition and Food Hygiene, School of Public Health, Bengbu Medical College, Bengbu 233030.
3. Anhui Province Key Laboratory of Immunology in Chronic Diseases, Bengbu 233030.
4. Anhui Province Key Laboratory of Immunology in Chronic Diseases, Bengbu 233030. liuhui@bbmc.edu.cn.
- Publication Type:Journal Article
- Keywords:
fatty acid oxidation;
perfluorooctanoic acid;
peroxisome proliferation factor activated receptor;
silent information regulator 1
- MeSH:
Animals;
Caprylates;
Fatty Acids/pharmacology*;
Fluorocarbons;
Lipid Metabolism;
Lipid Metabolism Disorders/metabolism*;
Liver/metabolism*;
Male;
PPAR gamma;
Rats;
Rats, Sprague-Dawley;
Sirtuin 1/metabolism*
- From:
Journal of Central South University(Medical Sciences)
2022;47(1):18-25
- CountryChina
- Language:English
-
Abstract:
OBJECTIVES:Perfluorooctanoic acid (PFOA) can cause lipid metabolism disorders in animal body and affect the lipolysis and synthesis of fatty acids. Peroxisome proliferators-activated receptor (PPAR) plays an extremely important role in this process. This study aims to explore the effects of PFOA on liver lipid metabolism disorders in Sprague Dewley (SD) rats and the expression of PPAR.
METHODS:A total of 40 male SD rats were randomly divided into 4 groups (n=10 in each group): a control group (ddH2O), a low-dose PFOA group [PFOA 1.25 mg/(kg·d)], a middle-dose PFOA group [PFOA 5.00 mg/(kg·d)], and a high-dose PFOA group [PFOA 20.00 mg/(kg·d)]. The rats were fed with normal diet, and PFOA exposure were performed by oral gavage for 14 days, and the rats were observed, weighted and recorded every day during the exposure. After the exposure, the blood was collected, and the livers were quickly stripped after the rats were killed. Part of the liver tissues were fixed in 4% paraformaldehyde for periodic acid-schiff (PAS) staining; the contents of HDLC, LDLC, TG, TC in serum and liver tissues, as well as the activities of their related enzymes were assayed; The expression levels of cyclic adenosine monophosphate-response element binding protein (Cbp), general control of amino acid synthesis 5-like 2 (Gcn5L2), peroxidation peroxisome proliferation factor activated receptor γ (PPAR), silent information regulator 1 (Sirt1) and human retinoid X receptor alpha 2 (Rxrα2) ) were detected by Western blotting.
RESULTS:After 14 days of PFOA exposure, the PAS staining positive particles in the cytoplasm and nucleus of SD rats in the medium and high dose groups were significantly reduced compared with the control group. The serum levels of LDLC and TC in the low-dose and middle-dose groups were significantly reduced compared with the control group (all P<0.05), while the high-dose group showed an increasing tendency, without siginificant difference (P>0.05), there was no significant difference in HDLC and TG (both P>0.05). The activities of alkaline phosphatase (AKP) and alanine aminotransferase (ALT) were increased significantly (both P<0.05) compared with control group; the ratio of ALT/aspartate aminotransferase (AST) in the high-dose group was increased significantly (P<0.05), there was no significant difference in LDH and TG (both P>0.05); the HDLC content in the liver tissues in the high-dose group was significantly reduced, compared with the control group (P<0.05); the TC contents in the liver tissues in the low, medium and high-dose groups were significantly increased (all P<0.05), there was no significant difference in LDLC and TG (both P>0.05); the AKP activity in the livers in the medium and high-dose groups was significantly increased (both P<0.05), there was no siginificant difference in LDH, ALT, and the ratio of ALT/AST (all P>0.05); the protein expression levels of Ppar γ, Cbp and Rxrα2 in the liver in the high dose groups were significantly down-regulated compared with the control group (all P<0.05), while the protein expression levels of Sirt1 were significantly up-regulated (all P<0.05).
CONCLUSIONS:PFOA exposure can cause lipid metabolism disorder and glycogen reduction in SD rat livers, which may be related to the activation of Sirt1 and inhibition of Ppar γ expression, leading to affecting the normal metabolism of fatty acids and promoting glycolysis.
