{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T01:32:00Z","timestamp":1772760720267,"version":"3.50.1"},"reference-count":41,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T00:00:00Z","timestamp":1627776000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["109-2311-B-492-002-MY3"],"award-info":[{"award-number":["109-2311-B-492-002-MY3"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["109-2327-B-002-005-"],"award-info":[{"award-number":["109-2327-B-002-005-"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Mitochondrial aldehyde dehydrogenase 2 (ALDH2) is a critical enzyme involved in ethanol clearance in acetaldehyde metabolism and plays a key role in protecting the liver. The ALDH2*2 mutation causes a significant decrease in acetaldehyde scavenging capacity, leading to the accumulation of acetaldehyde after consuming alcohol. The prevalence of the ALDH2*2 variant is in 45% of Taiwanese individuals. ALDH2 reportedly has protective properties on myocardial damage, stroke, and diabetic retina damage. However, the effects of ALDH2 in the modulation of metabolic syndromes remain unclear. This study evaluates the roles of ALDH2 in a high-fat-diet-induced metabolic syndrome in mice. Male (M) and female (F) wild-type (WT) and ALDH2 knock-in C57BL\/6J mice (4\u20135 weeks old) were fed a high-fat diet for 16 weeks. Results showed that the body and white-adipose-tissue weights were significantly increased in ALDH2-M compared to those in the other groups. We observed markedly elevated serum levels of alanine transaminase and glucose. Oral glucose-tolerance test and homeostasis-model assessment of insulin resistance (HOMA-IR) values were significantly higher in ALDH2-M mice than those in WT-M mice, with no observable differences in female mice. Abundant steatosis and inflammatory cells were observed in ALDH2-M, with significantly decreased expression of hepatic genes IRS2, GLUT4, and PGC-1\u03b1 compared to that in WT-M. ALDH2 gene mutation also affected the \u03b2-diversity of gut microbiota in ALDH2-M resulting in the decreased abundance of Actinobacteria and an increase in Deferribacteres. Our results suggest that potential changes in gut microbiota may be associated with the defective ALDH2 exacerbation of high-fat-diet-induced liver diseases in male mice. However, female mice were not affected, and sex hormones may be an important factor that requires further investigation.<\/jats:p>","DOI":"10.3390\/biology10080737","type":"journal-article","created":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T21:51:07Z","timestamp":1627854667000},"page":"737","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Aldehyde Dehydrogenase Mutation Exacerbated High-Fat-Diet-Induced Nonalcoholic Fatty Liver Disease with Gut Microbiota Remodeling in Male Mice"],"prefix":"10.3390","volume":"10","author":[{"given":"Sien-Sing","family":"Yang","sequence":"first","affiliation":[{"name":"Liver Center, Cathay General Hospital Medical Center, Taipei 106, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9705-4045","authenticated-orcid":false,"given":"Yi-Hsun","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei 100, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jui-Ting","family":"Hu","sequence":"additional","affiliation":[{"name":"Liver Center, Cathay General Hospital Medical Center, Taipei 106, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5591-0288","authenticated-orcid":false,"given":"Ching-Feng","family":"Chiu","sequence":"additional","affiliation":[{"name":"Graduate Institute of Metabolism and Obesity Sciences, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shao-Wen","family":"Hung","sequence":"additional","affiliation":[{"name":"Division of Animal Industry, Animal Technology Research Center, Agricultural Technology Research Institute, Miaoli 350, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-Chih","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Science and Biotechnology, Asia University, Taichung 413, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chien-Chao","family":"Chiu","sequence":"additional","affiliation":[{"name":"Division of Animal Industry, Animal Technology Research Center, Agricultural Technology Research Institute, Miaoli 350, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3718-9076","authenticated-orcid":false,"given":"Hsiao-Li","family":"Chuang","sequence":"additional","affiliation":[{"name":"National Laboratory Animal Center, National Applied Research Laboratories, Taipei 115, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4445","DOI":"10.1021\/bi9521093","article-title":"Possible role of liver cytosolic and mitochondrial aldehyde dehydrogenases in acetaldehyde metabolism","volume":"35","author":"Klyosov","year":"1996","journal-title":"Biochemistry"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1111\/acer.12215","article-title":"Dominance of the inactive Asian variant over activity and protein contents of mitochondrial aldehyde dehydrogenase 2 in human liver","volume":"38","author":"Lai","year":"2014","journal-title":"Alcohol. 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