Involvement of SREBPs in 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced disruption of lipid metabolism in male guinea pig

Journal Article · Sun Jun 15 04:00:00 EDT 2008 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2008.01.030· OSTI ID:21140862

Nishiumi, Shin; Yabushita, Yoshiyuki; Furuyashiki, Takashi ^[1]; Fukuda, Itsuko ^[2]; Ashida, Hitoshi ^[1]

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1. Department of Agrobioscience, Graduate School of Agricultural Science, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe, Hyogo 657-8501 (Japan)
2. Research Center for Food Safety and Security, Graduate School of Agricultural Science, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe, Hyogo 657-8501 (Japan)

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has multiple toxic effects causing a wasting syndrome characterized by a loss of body weight accompanied by a decrease in adipose tissue weight. To elucidate the mechanism behind this syndrome, we investigated the changes in lipid metabolism 7 and 21 days after a single intraperitoneal injection of TCDD at 1 {mu}g/kg body weight to male guinea pigs. TCDD caused the symptoms of the syndrome, body weight loss with a decrease in adipose tissue weight, while it increased the levels of triacylglycerols, total cholesterols, and free fatty acids in plasma. On day 7, TCDD decreased the levels of CCAAT/enhancer binding protein (C/EBP) {alpha}, peroxisome proliferator activated receptor {gamma}, and glucose transporter 4, adipogenesis-related factors, in adipose tissue, whereas the levels of retinoid X receptor {alpha}, C/EBP{beta}, C/EBP{delta}, and c-Myc remained unchanged. TCDD also reduced the levels of both p125 precursor and p68 active forms of sterol regulatory element binding protein (SREBP)-1 and -2, the lypogenesis-related factors, and downregulated their DNA binding activity in adipose tissue, while it raised the levels of their p68 active forms and increased their DNA binding activity in the liver. TCDD decreased mRNA and protein levels of acetyl-CoA carboxylase and HMG-CoA synthase in the liver and adipose tissue. Similar results were obtained on day 21. These results suggest that TCDD disrupts lipid metabolism through changes in the expression levels of the adipogenesis-related and lipogenesis-related proteins in the liver and adipose tissue, and SREBPs would be involved in the development of the wasting syndrome.

• OSTI ID: 21140862
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 3 Vol. 229; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ADIPOSE TISSUE
CARBOXYLASE
CARNITINE
CHOLESTEROL
DIOXIN
DNA
ELECTROPHORESIS
GLUCOSE
GUINEA PIGS
HYDROCARBONS
INTRAPERITONEAL INJECTION
LIPASES
LIPOPROTEINS
LIVER
METABOLISM
POLYMERASE CHAIN REACTION
RECEPTORS
TOXICITY
TRANSCRIPTION