In:
Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 38, No. Suppl_1 ( 2018-05)
Abstract:
Objective: The sorting receptor Sortilin functions in the regulation of glucose and lipid metabolism. Dysfunctional lipid uptake, storage, and metabolism contribute to several major human diseases including atherosclerosis and obesity. Sortilin associates with cardiovascular disease; however, the role of Sortilin in adipose tissue and lipid metabolism remains unclear. Approach and Results: Here we show that in the low-density lipoprotein receptor-deficient (Ldlr -/- ) atherosclerosis model, Sortilin deficiency ( Sort1 -/- ) in female mice inhibits intestinal Niemann-Pick type C1-Like 1 (Npc1l1) expression (-60.6 %, p 〈 0.01), reduces body (-17.2 %, p 〈 0.01) and white adipose tissue weight (-35.2 %, p 〈 0.05), and improves brown adipose tissue function partially via transcriptional downregulation of Krüppel-like factor 4 and Liver X receptor (Figure). Female Ldlr -/- Sort1 -/- mice on a high fat/cholesterol diet had elevated plasma Fibroblast growth factor 21 (+89.1 %, p 〈 0.05) and Adiponectin (+37.7 %, p 〈 0.01), an adipokine that when reduced is associated with obesity and cardiovascular disease related factors. Additionally, Sortilin deficiency suppressed cholesterol absorption in both human colon Caco-2 cells (-16.5 %, p 〈 0.05) and mouse ex vivo intestinal tissue (-16.9 %, p 〈 0.05) in a similar manner to treatment with the Npc1l1 inhibitor - ezetimibe. Conclusions: Together our findings support a novel role of Sortilin in energy regulation and lipid homeostasis in female mice, which may be a potential therapeutic target for obesity and cardiovascular disease.
Type of Medium:
Online Resource
ISSN:
1079-5642
,
1524-4636
DOI:
10.1161/atvb.38.suppl_1.595
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2018
detail.hit.zdb_id:
1494427-3
