Dennd5b-Deficient Mice are Resistant to PCSK9-Induced Hypercholesterolemia and Diet-Induced Hepatic Steatosis.
Dennd5b-Deficient Mice are Resistant to PCSK9-Induced Hypercholesterolemia and Diet-Induced Hepatic Steatosis.
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dennd5b缺陷小鼠对pcsk9诱导的高胆固醇血症和饮食诱导的肝脂肪变性具有抗性。
DOI：
10.1016/j.jlr.2022.100296
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发表时间：
2022-12
影响因子：
6.5
通讯作者：
Gordon, Scott M.
中科院分区：
文献类型：
--
作者：
Mobilia, Maura;Whitus, Callie;Karakashian, Alexander;Lu, Hong S.;Daugherty, Alan;Gordon, Scott M.
关键词：
Dennd5b plays a pivotal role in intestinal absorption of dietary lipids in mice and is associated with body mass index in humans. This study examined the impact of whole-body Dennd5b deletion on plasma lipid concentrations, atherosclerosis, and hepatic lipid metabolism in mice. Hypercholesterolemia was induced in Dennd5b−/− mice by infection with an adeno-associated virus expressing the proprotein convertase subtilisin/kexin type 9 serine protease (PCSK9) gain-of-function mutation (PCSK9D377Y) and feeding a Western diet for 12 weeks. Body weight and plasma lipid concentrations were monitored over 12 weeks, and then aortic atherosclerosis and hepatic lipid content were quantified. Compared to Dennd5b+/+ mice, Dennd5b−/− mice were resistant to diet-induced weight gain and PCSK9-induced hypercholesterolemia. Atherosclerosis quantified by en face analysis and in aortic root sections, revealed significantly smaller lesions in Dennd5b−/− compared to Dennd5b+/+ mice. Additionally, Dennd5b−/− mice had significantly less hepatic lipid content (triglyceride and cholesterol) compared to Dennd5b+/+ mice. To gain insight into the basis for reduced hepatic lipids, quantitative PCR was used to measure mRNA abundance of genes involved in hepatic lipid metabolism. Key genes involved in hepatic lipid metabolism and lipid storage were differentially expressed in Dennd5b−/− liver including Pparg, Cd36, and Pnpla3. These findings demonstrate a significant impact of Dennd5b on plasma and hepatic lipid concentrations and resistance to PCSK9-induced hypercholesterolemia in the absence of Dennd5b.
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DOI：
10.1161/atvbaha.116.307613
发表时间：
2016-09
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Lu H;Howatt DA;Balakrishnan A;Graham MJ;Mullick AE;Daugherty A
通讯作者：
Daugherty A
DOI：
10.2147/hmer.s125718
发表时间：
2017
期刊：
Hepatic medicine : evidence and research
影响因子：
--
作者：
Bruschi FV;Tardelli M;Claudel T;Trauner M
通讯作者：
Trauner M
影响因子：
5.4
作者：
Grygiel-Górniak B
通讯作者：
Grygiel-Górniak B
影响因子：
6.5
作者：
Millar, JS;Cromley, DA;Billheimer, JT
通讯作者：
Billheimer, JT
影响因子：
6.5
作者：
Lake, AC;Sun, Y;Gimeno, RE
通讯作者：
Gimeno, RE