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Sedentary lifestyle related exosomal release of Hotair from gluteal-femoral fat promotes intestinal cell proliferation.

Abstract：

:Pioneering epidemiological work has established strong association of sedentary lifestyle and obesity with the risk of colorectal cancer, while the detailed underlying mechanism remains unknown. Here we show that Hotair (HOX transcript antisense RNA) is a pro-adipogenic long non-coding RNA highly expressed in gluteal-femoral fat over other fat depots. Hotair knockout in adipose tissue results in gluteal-femoral fat defect. Squeeze of the gluteal-femoral fat induces intestinal proliferation in wildtype mice, while not in Hotair knockout mice. Mechanistically, squeeze of the gluteal-femoral fat induces exosomal Hotair secretion mainly by transcriptional upregulation of Hotair via NFκB. And increased exosomal Hotair in turn circulates in the blood and is partially endocytosed by the intestine, finally promoting the stemness and proliferation of intestinal stem/progenitor cells via Wnt activation. Clinically, obese subjects with sedentary lifestyle have much higher exosomal HOTAIR expression in the serum. These findings establish that sedentary lifestyle promotes exosomal Hotair release from the gluteal-femoral fat, which in turn facilitates intestinal stem and/or progenitor proliferation, raising a possible link between sedentary lifestyle with colorectal tumorigenesis.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Lu X,Bai D,Liu X,Zhou C,Yang G

doi

10.1038/srep45648

subject

Has Abstract

pub_date

2017-03-31 00:00:00

pages

45648

issn

2045-2322

pii

srep45648

journal_volume

7

pub_type

杂志文章

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