Scholarlink

<p>UbiA prenyltransferase domain containing 1 (<i>Ubiad1</i>) has the potential to affect cholesterol and phospholipid levels in different cell types. We previously identified <i>Ubiad1</i> as a candidate gene for regulating subcutaneous fat pad weight in a mouse genome-wide association study. Here we evaluated the relationship between <i>Ubiad1</i> and obesity-related traits in cohorts of humans and mice, and in <i>Ubiad1</i><sup>+/−</sup> mice fed a high-fat diet. In both humans and mice, adipose tissue <i>Ubiad1</i> mRNA expression correlated negatively with adiposity and positively with mitochondria-related genes. To determine the role of Ubiad1 in high-fat diet-induced obesity, we disrupted the <i>Ubiad1</i> gene in mice. Deletion of <i>Ubiad1</i> was embryonically lethal in C57BL/6&#xa0;N mice, preventing analysis of adult <i>Ubiad1</i><sup>−/−</sup> mice. Thus, male and female <i>Ubiad1</i><sup>+/+</sup> and <i>Ubiad1</i><sup>+/−</sup> mice were fed high-fat diet for 10 weeks, with no difference in weight gain and adipose tissue organ weights observed between the genotypes. Analysis of liver mRNA expression revealed that <i>Ubiad1</i> heterozygosis (<i>Ubiad1</i><sup>+/−</sup>) altered several pathways involved in lipid metabolism. Detailed lipid quantification with HPLC-qTOF/MS showed increased levels of hepatic ceramides in female <i>Ubiad1</i><sup><i>+/−</i></sup> mice, whereas phosphatidylglycerols, phosohatidylinositol and lysophosphatidylethanolamines were reduced in male <i>Ubiad1</i><sup><i>+/−</i></sup> mice. Our findings reveal sex-specific effects of <i>Ubiad1</i> expression on hepatic lipid metabolism.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Hepatic lipid metabolism is altered in Ubiad1+/− mice of both sexes

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年2月27日

查看全文
  • Ryoko Higa,
  • Shirin Pourteymour,
  • Pratibha S. Kolan,
  • Simon N. Dankel,
  • Johan Fernø,
  • Gunnar Mellgren,
  • Calvin Pan,
  • Marcus M. Seldin,
  • Aldons J. Lusis,
  • Christian A. Drevon,
  • Knut T. Dalen,
  • Frode A. Norheim

摘要

UbiA prenyltransferase domain containing 1 (Ubiad1) has the potential to affect cholesterol and phospholipid levels in different cell types. We previously identified Ubiad1 as a candidate gene for regulating subcutaneous fat pad weight in a mouse genome-wide association study. Here we evaluated the relationship between Ubiad1 and obesity-related traits in cohorts of humans and mice, and in Ubiad1+/− mice fed a high-fat diet. In both humans and mice, adipose tissue Ubiad1 mRNA expression correlated negatively with adiposity and positively with mitochondria-related genes. To determine the role of Ubiad1 in high-fat diet-induced obesity, we disrupted the Ubiad1 gene in mice. Deletion of Ubiad1 was embryonically lethal in C57BL/6 N mice, preventing analysis of adult Ubiad1−/− mice. Thus, male and female Ubiad1+/+ and Ubiad1+/− mice were fed high-fat diet for 10 weeks, with no difference in weight gain and adipose tissue organ weights observed between the genotypes. Analysis of liver mRNA expression revealed that Ubiad1 heterozygosis (Ubiad1+/−) altered several pathways involved in lipid metabolism. Detailed lipid quantification with HPLC-qTOF/MS showed increased levels of hepatic ceramides in female Ubiad1+/− mice, whereas phosphatidylglycerols, phosohatidylinositol and lysophosphatidylethanolamines were reduced in male Ubiad1+/− mice. Our findings reveal sex-specific effects of Ubiad1 expression on hepatic lipid metabolism.