Epigenetic Regulation of Hepatic Lipid Metabolism by DNA Methylation
Evidence
Adv Sci (Weinh). 2023 Jun 6:e2206068. doi: 10.1002/advs.202206068. Online ahead of print.
ABSTRACT
While extensive investigations have been devoted to the study of genetic pathways related to fatty liver diseases, much less is known about epigenetic mechanisms underlying these disorders. DNA methylation is an epigenetic link between environmental factors (e.g., diets) and complex diseases (e.g., non-alcoholic fatty liver disease). Here, it is aimed to study the role of DNA methylation in the regulation of hepatic lipid metabolism. A dynamic change in the DNA methylome in the liver of high-fat diet (HFD)-fed mice is discovered, including a marked increase in DNA methylation at the promoter of Beta-klotho (Klb), a co-receptor for the biological functions of fibroblast growth factor (FGF)15/19 and FGF21. DNA methyltransferases (DNMT) 1 and 3A mediate HFD-induced methylation at the Klb promoter. Notably, HFD enhances DNMT1 protein stability via a ubiquitination-mediated mechanism. Liver-specific deletion of Dnmt1 or 3a increases Klb expression and ameliorates HFD-induced hepatic steatosis. Single-nucleus RNA sequencing analysis reveals pathways involved in fatty acid oxidation in Dnmt1-deficient hepatocytes. Targeted demethylation at the Klb promoter increases Klb expression and fatty acid oxidation, resulting in decreased hepatic lipid accumulation. Up-regulation of methyltransferases by HFD may induce hypermethylation of the Klb promoter and subsequent down-regulation of Klb expression, resulting in the development of hepatic steatosis.
Food Res Int. 2024 Sep;192:114748. doi: 10.1016/j.foodres.2024.114748. Epub 2024 Jul 14.ABSTRACTMechanized production of Jiangxiangxing Baijiu (JB) stands as a pivotal trend in today's Baijiu industry....
Food Res Int. 2024 Sep;192:114803. doi: 10.1016/j.foodres.2024.114803. Epub 2024 Jul 19.ABSTRACTMannoproteins have traditionally been recognized as effective wine organoleptic modulators, however, ambiguous understanding of the...
Food Res Int. 2024 Sep;192:114769. doi: 10.1016/j.foodres.2024.114769. Epub 2024 Jul 16.ABSTRACTDeciphering the mechanisms underlying the direct association between fructose consumption and the onset and progression...
Food Res Int. 2024 Sep;192:114807. doi: 10.1016/j.foodres.2024.114807. Epub 2024 Jul 26.ABSTRACTAlternative protein sources have been required to meet the significant plant protein demand. Agro-industrial by-products...
Ann Hepatol. 2024 Aug 13:101534. doi: 10.1016/j.aohep.2024.101534. Online ahead of print.ABSTRACTINTRODUCTION AND OBJECTIVES: Autoimmune liver diseases (AILD) are rare causes hepatocellular carcinoma (HCC). and data...
Daru. 2024 Aug 15. doi: 10.1007/s40199-024-00533-y. Online ahead of print.ABSTRACTBACKGROUND: Loxoprofen has been actively used clinically to relieve musculoskeletal pain and inflammatory symptoms. However, there...
This website uses cookies to improve your experience. We'll assume you're ok with this, but you can opt-out if you wish. Cookie settingsACCEPT
Privacy & Cookies Policy
Privacy Overview
This website uses cookies to improve your experience while you navigate through the website. Out of these cookies, the cookies that are categorized as necessary are stored on your browser as they are essential for the working of basic functionalities of the website. We also use third-party cookies that help us analyze and understand how you use this website. These cookies will be stored in your browser only with your consent. You also have the option to opt-out of these cookies. But opting out of some of these cookies may have an effect on your browsing experience.
Necessary cookies are absolutely essential for the website to function properly. This category only includes cookies that ensures basic functionalities and security features of the website. These cookies do not store any personal information.
Any cookies that may not be particularly necessary for the website to function and is used specifically to collect user personal data via analytics, ads, other embedded contents are termed as non-necessary cookies. It is mandatory to procure user consent prior to running these cookies on your website.