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Exercise reduces inflammatory cell production and cardiovascular inflammation via instruction of hematopoietic progenitor cells.


ABSTRACT: A sedentary lifestyle, chronic inflammation and leukocytosis increase atherosclerosis; however, it remains unclear whether regular physical activity influences leukocyte production. Here we show that voluntary running decreases hematopoietic activity in mice. Exercise protects mice and humans with atherosclerosis from chronic leukocytosis but does not compromise emergency hematopoiesis in mice. Mechanistically, exercise diminishes leptin production in adipose tissue, augmenting quiescence-promoting hematopoietic niche factors in leptin-receptor-positive stromal bone marrow cells. Induced deletion of the leptin receptor in Prrx1-creERT2; Leprfl/fl mice reveals that leptin's effect on bone marrow niche cells regulates hematopoietic stem and progenitor cell (HSPC) proliferation and leukocyte production, as well as cardiovascular inflammation and outcomes. Whereas running wheel withdrawal quickly reverses leptin levels, the impact of exercise on leukocyte production and on the HSPC epigenome and transcriptome persists for several weeks. Together, these data show that physical activity alters HSPCs via modulation of their niche, reducing hematopoietic output of inflammatory leukocytes.

SUBMITTER: Frodermann V 

PROVIDER: S-EPMC6858591 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Exercise reduces inflammatory cell production and cardiovascular inflammation via instruction of hematopoietic progenitor cells.

Frodermann Vanessa V   Rohde David D   Courties Gabriel G   Severe Nicolas N   Schloss Maximilian J MJ   Amatullah Hajera H   McAlpine Cameron S CS   Cremer Sebastian S   Hoyer Friedrich F FF   Ji Fei F   van Koeverden Ian D ID   Herisson Fanny F   Honold Lisa L   Masson Gustavo Santos GS   Zhang Shuang S   Grune Jana J   Iwamoto Yoshiko Y   Schmidt Stephen P SP   Wojtkiewicz Gregory R GR   Lee I-Hsiu IH   Gustafsson Karin K   Pasterkamp Gerard G   de Jager Saskia C A SCA   Sadreyev Ruslan I RI   MacFadyen Jean J   Libby Peter P   Ridker Paul P   Scadden David T DT   Naxerova Kamila K   Jeffrey Kate L KL   Swirski Filip K FK   Nahrendorf Matthias M  

Nature medicine 20191107 11


A sedentary lifestyle, chronic inflammation and leukocytosis increase atherosclerosis; however, it remains unclear whether regular physical activity influences leukocyte production. Here we show that voluntary running decreases hematopoietic activity in mice. Exercise protects mice and humans with atherosclerosis from chronic leukocytosis but does not compromise emergency hematopoiesis in mice. Mechanistically, exercise diminishes leptin production in adipose tissue, augmenting quiescence-promot  ...[more]

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