Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
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Effects of maternal cigarette smoke exposure on the progression of nonalcoholic steatohepatitis in offspring mice

  • Daram, Yang (Biosafety Research Institute and Laboratory of Veterinary Pathology, College of Veterinary Medicine, Jeonbuk National University) ;
  • Jong Won, Kim (Biosafety Research Institute and Laboratory of Veterinary Pathology, College of Veterinary Medicine, Jeonbuk National University) ;
  • Hyuneui, Jeong (Biosafety Research Institute and Laboratory of Veterinary Pathology, College of Veterinary Medicine, Jeonbuk National University) ;
  • Min Seok, Kim (Inhalation Toxicology Center, Jeonbuk Department of Inhalation Research, Korea Institute of Toxicology) ;
  • Chae Woong, Lim (Biosafety Research Institute and Laboratory of Veterinary Pathology, College of Veterinary Medicine, Jeonbuk National University) ;
  • Kyuhong, Lee (Inhalation Toxicology Center, Jeonbuk Department of Inhalation Research, Korea Institute of Toxicology) ;
  • Bumseok, Kim (Biosafety Research Institute and Laboratory of Veterinary Pathology, College of Veterinary Medicine, Jeonbuk National University)
  • Received : 2022.05.30
  • Accepted : 2022.08.22
  • Published : 2023.01.15
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Abstract

Cigarette smoke (CS) is a dominant carcinogenic agent in a variety of human cancers. CS exposure during pregnancy can adversely affect the fetus. Non-alcoholic fatty liver disease (NAFLD) is considered as a hepatic manifestation of a metabolic disorder, and ranges from simple steatosis to cirrhosis leading to hepatocellular carcinoma. Non-alcoholic steatohepatitis (NASH) is a more severe phase of NAFLD. Recently, there is increasing apprehension about the CS-related chronic liver diseases. Therefore, we examined whether maternal CS exposure could affect the pathogenesis of NASH in offspring. Mainstream CS (MSCS) was exposed to pregnant C57BL/6 mice via nose-only inhalation for 2 h/day, 5 days/week for 2 weeks from day 6 to 17 of gestation at 0, 300, or 600 ㎍/L. Three-week-old male offspring mice were fed methionine and choline-supplemented (MCS) diet or methionine and choline-deficient including high-fat (MCDHF) diet for 6 weeks to induce NASH. Maternal MSCS exposure increased the severity of NASH by increasing serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, hepatic total cholesterol (TC) and triglyceride (TG) levels, pro-inflammation, fibrosis, and steatosis in offspring mice. Especially, maternal MSCS exposure significantly downregulated the phosphorylation of AMP-activated protein kinase (AMPK) in MCDHF diet-fed offspring mice. Subsequently, the protein levels of sterol regulatory element-binding protein (SREBP)-1c and stearoyl-CoA desaturase-1 (SCD1) were upregulated by maternal MSCS exposure. In conclusion, maternal MSCS exposure exacerbates the progression of NASH by modulating lipogenesis on offspring mice.

Keywords

Acknowledgement

This study was supported by grants (No. 21203MFDS318) from the Ministry of Food and Drug Safety, Republic of Korea and the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) (HI20C0209) (J-W.K.) funded by the Ministry of Health & Welfare, Republic of Korea.

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