title: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, 710032, China.|State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an, 710032, China.|The 323rd Hospital, PLA, Xi'an, 710043, China.
authors.forename: Xiaozhao
authors.initials: X
authors.lastname: Lu
authors.affiliation: The 323rd Hospital, PLA, Xi'an, 710043, China.|Department of Physiology, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Danna
authors.initials: D
authors.lastname: Bai
authors.affiliation: Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, 710032, China.|State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an, 710032, China.|State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Xiangwei
authors.initials: X
authors.lastname: Liu
authors.affiliation: Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, 56 Lingyuanxi Road, Guangzhou, 510055, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, 710032, China.|State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Guodong
authors.initials: G
authors.lastname: Yang
mesh_terms: D050156:Adipogenesis; D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D000818:Animals; D002081:Buttocks / Q000196:embryology / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000378:metabolism; D055354:Exosomes / Q000378:metabolism*; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000097:blood; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D057185:Sedentary Behavior
chemical_list: C000608169:HOTAIR long non-coding RNA, mouse; D062085:RNA, Long Noncoding