Abstract
White adipose tissue not only serves as a reservoir for energy storage but also secretes a variety of hormonal signals and modulates systemic metabolism. A substantial amount of adipose tissue develops in early postnatal life, providing exceptional access to the formation of this important tissue. Although a number of factors have been identified that can modulate the differentiation of progenitor cells into mature adipocytes in cell-autonomous assays, it remains unclear which are connected to physiological extracellular inputs and are most relevant to tissue formation in vivo. Here, we elucidate that mature adipocytes themselves signal to adipose depot–resident progenitor cells to direct depot formation in early postnatal life and gate adipogenesis when the tissue matures. Our studies revealed that as the adipose depot matures, a signal generated in mature adipocytes is produced, converges on progenitor cells to regulate the cytoskeletal protein MYH9, and attenuates the rate of adipogenesis in vivo.
Highlights
White adipose tissue (WAT) is a dynamic tissue that influences a variety of important physiological processes, including energy storage and insulin signaling, and secretes a number of endocrine and paracrine factors with broad effects [1,2,3,4]
To test whether ADAMTS1 has a role in regulating the development of adipose depots, we took advantage of the fact that a substantial portion of WAT develops during the postnatal period
Given what is known about the influence of ADAMTS1 on adipogenesis [8, 10], these results are consistent with a model where ADAMTS1 coordinates the reduction in adipogenesis that occurs as the WAT depot transitions from developing to homeostasis
Summary
White adipose tissue (WAT) is a dynamic tissue that influences a variety of important physiological processes, including energy storage and insulin signaling, and secretes a number of endocrine and paracrine factors with broad effects [1,2,3,4]. Adipogenesis has been heavily studied using reductionist in vitro and tissue culture model systems. These studies identified a number of factors that can modulate adipogenesis within the context of cell-autonomous in vitro assays [5,6,7]. Advantages of the postnatal timing of the development of adipose tissue have not been fully leveraged to elucidate the in vivo mechanisms that regulate this important developmental process. The relevant intracellular pathways and mechanisms in APCs that respond to extracellular signals and regulate adipogenesis have not been fully defined
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