Transcriptional control of intestinal cholesterol absorption, adipose energy expenditure and lipid handling by Sortilin.
Sci Rep
; 8(1): 9006, 2018 06 13.
Article
in En
| MEDLINE
| ID: mdl-29899496
ABSTRACT
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. Here we show that in the low-density lipoprotein receptor-deficient (Ldlr-/-) atherosclerosis model, Sortilin deficiency (Sort1-/-) in female mice suppresses Niemann-Pick type C1-Like 1 (Npc1l1) mRNA levels, reduces body and white adipose tissue weight, and improves brown adipose tissue function partially via transcriptional downregulation of Krüppel-like factor 4 and Liver X receptor. Female Ldlr-/-Sort1-/- mice on a high-fat/cholesterol diet had elevated plasma Fibroblast growth factor 21 and Adiponectin, an adipokine that when reduced is associated with obesity and cardiovascular disease-related factors. Additionally, Sort1 deficiency suppressed cholesterol absorption in both female mice ex vivo intestinal tissue and human colon Caco-2 cells in a similar manner to treatment with the NPC1L1 inhibitor ezetimibe. 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Adipose Tissue
/
Gene Expression Regulation
/
Cholesterol
/
Adaptor Proteins, Vesicular Transport
/
Energy Metabolism
/
Lipid Metabolism
Type of study:
Health_economic_evaluation
/
Prognostic_studies
Limits:
Animals
/
Female
/
Humans
/
Male
Language:
En
Journal:
Sci Rep
Year:
2018
Document type:
Article
Affiliation country:
United States