Cholic Acid Enhances Visceral Adiposity, Atherosclerosis and Nonalcoholic Fatty Liver Disease in Microminipigs
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- Yamada Sohsuke
- Department of Pathology, Kagoshima University Graduate School of Medical and Dental Sciences
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- Kawaguchi Hiroaki
- Department of Hygiene and Health Promotion Medicine, Kagoshima University Graduate School of Medical and Dental Sciences
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- Yamada Tomonobu
- Shin Nippon Biomedical Laboratories, Ltd.
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- Guo Xin
- Department of Pathology, Kagoshima University Graduate School of Medical and Dental Sciences
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- Matsuo Kei
- Department of Pathology, Kagoshima University Graduate School of Medical and Dental Sciences
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- Hamada Taiji
- Department of Pathology, Kagoshima University Graduate School of Medical and Dental Sciences
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- Miura Naoki
- Veterinary Teaching Hospital, Joint Faculty of Veterinary Medicine, Kagoshima University
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- Tasaki Takashi
- Department of Pathology, Kagoshima University Graduate School of Medical and Dental Sciences
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- Tanimoto Akihide
- Department of Pathology, Kagoshima University Graduate School of Medical and Dental Sciences
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説明
<p>Aim: We have recently established a novel swine model for studies of atherosclerosis using MicrominipigsTM (µMPs) fed a high-fat/high-cholesterol diet (HcD). Using this swine model, we re-evaluated the effects of dietary cholic acid (CA) on serum lipid profile, atherosclerosis and hepatic injuries.</p><p>Methods: The µMPs were fed HcD supplemented with 0.7% CA (HcD＋CA) for eight weeks, and the effect of CA on serum lipoprotein levels, expression of oxidative stress markers, adiposity and lesion formation in the aorta, liver, and other organs was investigated.</p><p>Results: The HcD＋CA-fed group exhibited more visceral adiposity, progression of atherosclerosis and higher serum levels of oxidative stress markers than the HcD-fed group, even though they showed similar serum lipid levels. The liver demonstrated increased lipid accumulation, higher expression of oxidative stress markers, accelerated activation of foamy Kupffer cells and stellate cells, and increased hepatocyte apoptosis, indicating non-alcoholic fatty liver disease (NAFLD). Intriguingly, foamy macrophage mobilization was observed in various organs, including the reticuloendothelial system, pulmonary capillary vessels and skin very often in HcD＋CA-fed µMPs.</p><p>Conclusion: To our knowledge, this is the first large animal model, in which visceral obesity, NAFLD and atherosclerosis are concomitantly induced by dietary manipulation. These data suggest the detrimental effects of CA, potentially through local and systemic activation of oxidative stress-induced signaling to macrophage mobilization, on the acceleration of visceral adiposity, atherosclerosis and NAFLD.</p>
収録刊行物
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- Ｊｏｕｒｎａｌ ｏｆ Ａｔｈｅｒｏｓｃｌｅｒｏｓｉｓ ａｎｄ Ｔｈｒｏｍｂｏｓｉｓ
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Ｊｏｕｒｎａｌ ｏｆ Ａｔｈｅｒｏｓｃｌｅｒｏｓｉｓ ａｎｄ Ｔｈｒｏｍｂｏｓｉｓ 24 (11), 1150-1166, 2017
一般社団法人 日本動脈硬化学会
