Vascular Disease Is Associated With the Expression of Genes for Intestinal Cholesterol Transport and Metabolism

Widdowson, William M; McGowan, Anne; Phelan, J.J.; Boran, Gerard; Reynolds, John V.; Gibney, James

doi:10.1210/jc.2016-2728

Cited by 3 publications

(2 citation statements)

References 41 publications

(32 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consistent with our findings, expression of Npc1l1 and sterol absorption are increased by glucose 35,40 and nuclear levels of SREBF2 are increased by feeding and insulin 41 . Inhibition by SHP of other known SHPinteracting factors whose binding motifs were detected in the Npc1l1 promoter, such as, LRH-1 or AhR 14,36 , may contribute to Npc1l1 repression, but SHP inhibition of SREBF2 is likely primary, given the importance of SREBF2 in the regulation of Npc1l1 and sterol levels [35][36][37][38] .…”

Section: Discussionmentioning

confidence: 99%

“…Binding motifs for several factors, including SREBFs, were identified in these regions ( Figure 6A, left). Since multiple SREs were detected at the Npc1l1 gene promoter, intestinal expression of Npc1l1 is activated by SREBF2 and to a much lesser extent by SREBF1 [35][36][37] , and SREBF2 expression strongly correlates with NPC1L1 expression in hyperlipidemia patients 38 , we focused mechanistic studies on SREBF2.…”

Section: Srebf2 Activation Of Expression Of Npc1l1 In Intestinal Cellmentioning

confidence: 99%

See 1 more Smart Citation

Small Heterodimer Partner and Fibroblast Growth Factor 19 Inhibit Expression of NPC1L1 in Mouse Intestine and Cholesterol Absorption

et al. 2019

View full text Add to dashboard Cite

Background & Aims: The nuclear receptor subfamily 0 group B member 2 (NR0B2, also called SHP) is expressed at high levels in liver and intestine. Postprandial fibroblast growth factor 19 (human FGF19, mouse FGF15) signaling increases the transcriptional activity of SHP. We studied the functions of SHP and FGF19 in intestines of mice, including their regulation of expression of the cholesterol transporter NPC1-like intracellular cholesterol transporter 1 (NPC1L1) and cholesterol absorption. Methods: We performed histologic and biochemical analyses of intestinal tissues from C57BL/6 and SHP-knockout mice and performed RNA-seq analyses to identify genes regulated by SHP. The effects of fasting and refeeding on intestinal expression of NPC1L1 was examined in C57BL/6, SHP-knockout, and FGF15-knockout mice. Mice were given FGF19 daily for 1 week; fractional cholesterol absorption, cholesterol and bile acid (BA) levels, and composition of BAs were measured. Intestinal organoids were generated from C57BL/6 and SHP-knockout mice and cholesterol uptake was measured. Luciferase reporter assays were performed with HT29 cells.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Srebf2 Activation Of Expression Of Npc1l1 In Intestinal Cellmentioning

confidence: 99%

Small Heterodimer Partner and Fibroblast Growth Factor 19 Inhibit Expression of NPC1L1 in Mouse Intestine and Cholesterol Absorption

et al. 2019

View full text Add to dashboard Cite

show abstract

A single, high-fat meal adversely affects postprandial endothelial function: a systematic review and meta-analysis

Fewkes

Kellow

Cowan

et al. 2022

The American Journal of Clinical Nutrition

View full text Add to dashboard Cite

Background Endothelial dysfunction is a predictive risk factor for the development of atherosclerosis and is assessed by flow-mediated dilation (FMD). Although it is known that nitric oxide-dependent endothelial dysfunction occurs after consuming a high-fat meal, the magnitude of the effect and the factors that affect the response are unquantified. Objectives To conduct a systematic review and meta-analysis exploring the quantitative effect of a single high-fat meal on endothelial function and determine the factors that modify the FMD response. Design Six databases were systematically searched for original research published up to January 2022. Eligible studies measured fasting and postprandial FMD following consumption of a high-fat meal. Meta-regression was used to analyze the effect of moderator variables. The protocol was pre-registered in the Prospero database (ID# CRD42020187244). Results There were 131 studies included of which 90 were suitable for quantitative meta-analysis. A high-fat meal challenge transiently caused endothelial dysfunction, decreasing postprandial FMD at 2-hours: -1.02 percentage points (pp) (95% CI: [-1.34, -0.70], P < 0.01, I2 = 93.3%), 3-hours: -1.04 pp ([-1.48, -0.59], P < 0.001, I2 = 84.5%), and 4-hours: -1.19 pp ([-1.53, -0.84], P < 0.01, I2 = 94.6%). Younger, healthy-weight participants exhibited a greater postprandial reduction in FMD% than older, heavier, at-risk groups after a high-fat meal (P < 0.05). Percent fat of the meals was inversely associated with the magnitude of postprandial change in FMD at 3-hours (P < 0.01). Conclusion A single high-fat meal adversely impacts endothelial function, with the magnitude of the impact on postprandial FMD moderated by fasting FMD, participant age, body mass index, and fat content of the meal. Recommendations are made to standardize the design of future postprandial FMD studies and optimize interpretation of results, as high-fat meals are commonly used in clinical studies as a challenge to assess endothelial function and therapeutics.

show abstract

Control of intestinal lipoprotein secretion by dietary carbohydrates

Stahel

Xiao²,

Lewis³

2018

Current Opinion in Lipidology

View full text Add to dashboard Cite

show abstract

Vascular Disease Is Associated With the Expression of Genes for Intestinal Cholesterol Transport and Metabolism

Cited by 3 publications

References 41 publications

Small Heterodimer Partner and Fibroblast Growth Factor 19 Inhibit Expression of NPC1L1 in Mouse Intestine and Cholesterol Absorption

Small Heterodimer Partner and Fibroblast Growth Factor 19 Inhibit Expression of NPC1L1 in Mouse Intestine and Cholesterol Absorption

A single, high-fat meal adversely affects postprandial endothelial function: a systematic review and meta-analysis

Control of intestinal lipoprotein secretion by dietary carbohydrates

Contact Info

Product

Resources

About