Abstract
White adipose tissue (WAT) expansion in obesity occurs through enlargement of preexisting adipocytes (hypertrophy) and through formation of new adipocytes (adipogenesis). Adipogenesis results in WAT hyperplasia, smaller adipocytes and a metabolically more favourable form of obesity. How obesogenic WAT hyperplasia is induced remains, however, poorly understood. Here, we show that the mechanosensitive cationic channel Piezo1 mediates diet-induced adipogenesis. Mice lacking Piezo1 in mature adipocytes demonstrated defective differentiation of preadipocyte into mature adipocytes when fed a high fat diet (HFD) resulting in larger adipocytes, increased WAT inflammation and reduced insulin sensitivity. Opening of Piezo1 in mature adipocytes causes the release of the adipogenic fibroblast growth factor 1 (FGF1), which induces adipocyte precursor differentiation through activation of the FGF-receptor-1. These data identify a central feed-back mechanism by which mature adipocytes control adipogenesis during the development of obesity and suggest Piezo1-mediated adipocyte mechano-signalling as a mechanism to modulate obesity and its metabolic consequences.
Highlights
White adipose tissue (WAT) expansion in obesity occurs through enlargement of preexisting adipocytes and through formation of new adipocytes
In murine adipocytes, Yoda[1] and short term exposure to a hypotonic solution induced a significant increase in the free cytosolic Ca2+-concentration (Fig. 1d, e), an effect which was greatly reduced in adipocytes of tamoxifeninduced adipocyte-specific Piezo1-deficient mice (Ad-Piezo1-KO) (Fig. 1d, e)
Since adipocytes show a significant increase in size already after 2 days of high fat diet (HFD) feeding (Supplementary Fig. 1e, f), we used the fluorescent lipid tension sensor, FliptR29 to determine membrane tension in mature adipocytes
Summary
White adipose tissue (WAT) expansion in obesity occurs through enlargement of preexisting adipocytes (hypertrophy) and through formation of new adipocytes (adipogenesis). Opening of Piezo[1] in mature adipocytes causes the release of the adipogenic fibroblast growth factor 1 (FGF1), which induces adipocyte precursor differentiation through activation of the FGF-receptor-1. These data identify a central feed-back mechanism by which mature adipocytes control adipogenesis during the development of obesity and suggest Piezo1mediated adipocyte mechano-signalling as a mechanism to modulate obesity and its metabolic consequences. Multiple signaling pathways and mediators have been described which regulate pre-adipocyte proliferation and differentiation into mature adipocytes such as bone morphogenetic protein signaling and WNT signaling or insulin-like growth factor 18,16–18 It is, incompletely understood through which mechanisms adipocyte progenitor cell proliferation and differentiation is controlled by systemic and local factors. Since we observed high expression of Piezo[1] in mature white adipocytes we speculated that Piezo1-mediated mechanosignalling is involved in adipose tissue function and remodeling
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