Elevated circulating homocysteine (Hcy) has been proposed to be associated with non-alcoholic fatty liver disease (NAFLD). It is also reported that Hcy causes protein misfolding in the endoplasmic reticulum (ER). In this study, we used a high methionine diet (HMD)-fed mouse model and cultured primary hepatocytes to investigate the effects of Hcy on hepatic lipids metabolism. C57BL/6J mice received either standard chow diet (CT, n = 10) or diet supplemented with 2% methionine (MET, n = 10) for 16 weeks. In in vitro experiments, cultured mouse primary hepatocytes were treated with Hcy, or Hcy combined with 4-phenylbutyric acid (4-PBA), or tunicamycin (TM), respectively. HMD-fed mice exhibited a mild increase in plasma Hcy level. There was no significant difference of body weight gain between the two groups. Nevertheless, HMD feeding increased epididymal fat/body weight ratio, elevated plasma triglyceride (TG) level, and decreased high-density lipoprotein cholesterol (HDL) level. Similarly, mice on HMD displayed higher liver/body weight ratio, plasma aspartate aminotransferase (AST) and its ratio to alanine aminotransferase (ALT), which was supported by the morphological observations of hepatic triglyceride accumulation in liver tissue as well as primary hepatocytes. Activation of the sterol response element-binding protein 1c (SREBP1c) in Hcy-treated hepatocytes with increased expression of genes involved in hepatic de novo lipogenesis was partially reduced by pretreatment of 4-PBA. Hcy-induced ER stress was also ameliorated by 4-PBA pretreatment, thus demonstrating an important role of Hcy-induced ER stress response in hepatic steatosis. These findings suggest that elevated Hcy was a critical factor in the pathogenesis of NAFLD. Activation of the ER stress response may be involved in Hcy-induced hepatic steatosis.
机构:
Konkuk Univ, Coll Vet Med, Ctr Hlth 1, Seoul 05029, South KoreaKonkuk Univ, Coll Vet Med, Ctr Hlth 1, Seoul 05029, South Korea
Kim, Dong-Hyeon
Kim, Hyunsook
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Hanyang Univ, Coll Human Ecol, Dept Food & Nutr, 222 Wangsimni Ro, Seoul 04763, South KoreaKonkuk Univ, Coll Vet Med, Ctr Hlth 1, Seoul 05029, South Korea
Kim, Hyunsook
Jeong, Dana
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Konkuk Univ, Coll Vet Med, Ctr Hlth 1, Seoul 05029, South KoreaKonkuk Univ, Coll Vet Med, Ctr Hlth 1, Seoul 05029, South Korea
Jeong, Dana
Kang, Il-Byeong
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Konkuk Univ, Coll Vet Med, Ctr Hlth 1, Seoul 05029, South KoreaKonkuk Univ, Coll Vet Med, Ctr Hlth 1, Seoul 05029, South Korea
Kang, Il-Byeong
Chon, Jung-Whan
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h-index: 0
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Konkuk Univ, Coll Vet Med, Ctr Hlth 1, Seoul 05029, South Korea
US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR USAKonkuk Univ, Coll Vet Med, Ctr Hlth 1, Seoul 05029, South Korea
Chon, Jung-Whan
Kim, Hong-Seok
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Konkuk Univ, Coll Vet Med, Ctr Hlth 1, Seoul 05029, South KoreaKonkuk Univ, Coll Vet Med, Ctr Hlth 1, Seoul 05029, South Korea
Kim, Hong-Seok
Song, Kwang-Young
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Konkuk Univ, Coll Vet Med, Ctr Hlth 1, Seoul 05029, South KoreaKonkuk Univ, Coll Vet Med, Ctr Hlth 1, Seoul 05029, South Korea
Song, Kwang-Young
Seo, Kun-Ho
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Konkuk Univ, Coll Vet Med, Ctr Hlth 1, Seoul 05029, South KoreaKonkuk Univ, Coll Vet Med, Ctr Hlth 1, Seoul 05029, South Korea
机构:
Gyeongsang Natl Univ, Sch Med, Dept Anat & Convergence Med Sci, Inst Hlth Sci,Bio Antiaging Med Res Ctr, Jinju 52727, South KoreaGyeongsang Natl Univ, Sch Med, Dept Anat & Convergence Med Sci, Inst Hlth Sci,Bio Antiaging Med Res Ctr, Jinju 52727, South Korea
Jung, Soonwoong
Son, Hyeonwi
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Gyeongsang Natl Univ, Sch Med, Dept Anat & Convergence Med Sci, Inst Hlth Sci,Bio Antiaging Med Res Ctr, Jinju 52727, South KoreaGyeongsang Natl Univ, Sch Med, Dept Anat & Convergence Med Sci, Inst Hlth Sci,Bio Antiaging Med Res Ctr, Jinju 52727, South Korea
Son, Hyeonwi
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Hwang, Chung Eun
Cho, Kye Man
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Gyeongnam Natl Univ Sci & Technol, Dept Food Sci, Jinju 52725, South KoreaGyeongsang Natl Univ, Sch Med, Dept Anat & Convergence Med Sci, Inst Hlth Sci,Bio Antiaging Med Res Ctr, Jinju 52727, South Korea
Cho, Kye Man
Park, Sang Won
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Gyeongsang Natl Univ, Inst Hlth Sci, Dept Pharmacol & Convergence Med Sci, Bio Antiaging Med Res Ctr,Sch Med, Jinju, South KoreaGyeongsang Natl Univ, Sch Med, Dept Anat & Convergence Med Sci, Inst Hlth Sci,Bio Antiaging Med Res Ctr, Jinju 52727, South Korea
Park, Sang Won
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Kim, Hwajin
Kim, Hyun Joon
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Gyeongsang Natl Univ, Sch Med, Dept Anat & Convergence Med Sci, Inst Hlth Sci,Bio Antiaging Med Res Ctr, Jinju 52727, South KoreaGyeongsang Natl Univ, Sch Med, Dept Anat & Convergence Med Sci, Inst Hlth Sci,Bio Antiaging Med Res Ctr, Jinju 52727, South Korea
机构:
Chinese Acad Sci, Inst Zool, Lab Mol Toxicol, State Key Lab Integrated Management Pest Insects &, Beijing 100101, Peoples R ChinaChinese Acad Sci, Inst Zool, Lab Mol Toxicol, State Key Lab Integrated Management Pest Insects &, Beijing 100101, Peoples R China
Li, Jing
Wu, Yi-Jun
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Chinese Acad Sci, Inst Zool, Lab Mol Toxicol, State Key Lab Integrated Management Pest Insects &, Beijing 100101, Peoples R China
Chinese Acad Sci, Inst Zool, 1-5 Beichenxilu Rd, Beijing 100101, Peoples R ChinaChinese Acad Sci, Inst Zool, Lab Mol Toxicol, State Key Lab Integrated Management Pest Insects &, Beijing 100101, Peoples R China
机构:
Konkuk Univ, Coll Vet Med, Ctr Hlth 1, Seoul 05029, South KoreaKonkuk Univ, Coll Vet Med, Ctr Hlth 1, Seoul 05029, South Korea
Kim, Dong-Hyeon
Kim, Hyunsook
论文数: 0引用数: 0
h-index: 0
机构:
Hanyang Univ, Coll Human Ecol, Dept Food & Nutr, 222 Wangsimni Ro, Seoul 04763, South KoreaKonkuk Univ, Coll Vet Med, Ctr Hlth 1, Seoul 05029, South Korea
Kim, Hyunsook
Jeong, Dana
论文数: 0引用数: 0
h-index: 0
机构:
Konkuk Univ, Coll Vet Med, Ctr Hlth 1, Seoul 05029, South KoreaKonkuk Univ, Coll Vet Med, Ctr Hlth 1, Seoul 05029, South Korea
Jeong, Dana
Kang, Il-Byeong
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h-index: 0
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Konkuk Univ, Coll Vet Med, Ctr Hlth 1, Seoul 05029, South KoreaKonkuk Univ, Coll Vet Med, Ctr Hlth 1, Seoul 05029, South Korea
Kang, Il-Byeong
Chon, Jung-Whan
论文数: 0引用数: 0
h-index: 0
机构:
Konkuk Univ, Coll Vet Med, Ctr Hlth 1, Seoul 05029, South Korea
US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR USAKonkuk Univ, Coll Vet Med, Ctr Hlth 1, Seoul 05029, South Korea
Chon, Jung-Whan
Kim, Hong-Seok
论文数: 0引用数: 0
h-index: 0
机构:
Konkuk Univ, Coll Vet Med, Ctr Hlth 1, Seoul 05029, South KoreaKonkuk Univ, Coll Vet Med, Ctr Hlth 1, Seoul 05029, South Korea
Kim, Hong-Seok
Song, Kwang-Young
论文数: 0引用数: 0
h-index: 0
机构:
Konkuk Univ, Coll Vet Med, Ctr Hlth 1, Seoul 05029, South KoreaKonkuk Univ, Coll Vet Med, Ctr Hlth 1, Seoul 05029, South Korea
Song, Kwang-Young
Seo, Kun-Ho
论文数: 0引用数: 0
h-index: 0
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Konkuk Univ, Coll Vet Med, Ctr Hlth 1, Seoul 05029, South KoreaKonkuk Univ, Coll Vet Med, Ctr Hlth 1, Seoul 05029, South Korea
机构:
Gyeongsang Natl Univ, Sch Med, Dept Anat & Convergence Med Sci, Inst Hlth Sci,Bio Antiaging Med Res Ctr, Jinju 52727, South KoreaGyeongsang Natl Univ, Sch Med, Dept Anat & Convergence Med Sci, Inst Hlth Sci,Bio Antiaging Med Res Ctr, Jinju 52727, South Korea
Jung, Soonwoong
Son, Hyeonwi
论文数: 0引用数: 0
h-index: 0
机构:
Gyeongsang Natl Univ, Sch Med, Dept Anat & Convergence Med Sci, Inst Hlth Sci,Bio Antiaging Med Res Ctr, Jinju 52727, South KoreaGyeongsang Natl Univ, Sch Med, Dept Anat & Convergence Med Sci, Inst Hlth Sci,Bio Antiaging Med Res Ctr, Jinju 52727, South Korea
Son, Hyeonwi
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Hwang, Chung Eun
Cho, Kye Man
论文数: 0引用数: 0
h-index: 0
机构:
Gyeongnam Natl Univ Sci & Technol, Dept Food Sci, Jinju 52725, South KoreaGyeongsang Natl Univ, Sch Med, Dept Anat & Convergence Med Sci, Inst Hlth Sci,Bio Antiaging Med Res Ctr, Jinju 52727, South Korea
Cho, Kye Man
Park, Sang Won
论文数: 0引用数: 0
h-index: 0
机构:
Gyeongsang Natl Univ, Inst Hlth Sci, Dept Pharmacol & Convergence Med Sci, Bio Antiaging Med Res Ctr,Sch Med, Jinju, South KoreaGyeongsang Natl Univ, Sch Med, Dept Anat & Convergence Med Sci, Inst Hlth Sci,Bio Antiaging Med Res Ctr, Jinju 52727, South Korea
Park, Sang Won
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Kim, Hwajin
Kim, Hyun Joon
论文数: 0引用数: 0
h-index: 0
机构:
Gyeongsang Natl Univ, Sch Med, Dept Anat & Convergence Med Sci, Inst Hlth Sci,Bio Antiaging Med Res Ctr, Jinju 52727, South KoreaGyeongsang Natl Univ, Sch Med, Dept Anat & Convergence Med Sci, Inst Hlth Sci,Bio Antiaging Med Res Ctr, Jinju 52727, South Korea
机构:
Chinese Acad Sci, Inst Zool, Lab Mol Toxicol, State Key Lab Integrated Management Pest Insects &, Beijing 100101, Peoples R ChinaChinese Acad Sci, Inst Zool, Lab Mol Toxicol, State Key Lab Integrated Management Pest Insects &, Beijing 100101, Peoples R China
Li, Jing
Wu, Yi-Jun
论文数: 0引用数: 0
h-index: 0
机构:
Chinese Acad Sci, Inst Zool, Lab Mol Toxicol, State Key Lab Integrated Management Pest Insects &, Beijing 100101, Peoples R China
Chinese Acad Sci, Inst Zool, 1-5 Beichenxilu Rd, Beijing 100101, Peoples R ChinaChinese Acad Sci, Inst Zool, Lab Mol Toxicol, State Key Lab Integrated Management Pest Insects &, Beijing 100101, Peoples R China