4.7 Review

FGF10 and Lipofibroblasts in Lung Homeostasis and Disease: Insights Gained From the Adipocytes

Journal

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2021.645400

Keywords

FGF10; adipocytes; adipocyte-like cells; stem cell; lipofibroblast; myofibroblast; lung regeneration; repair

Funding

  1. Wenzhou Medical University
  2. Interventional Pulmonary Key Laboratory of Zhejiang Province
  3. Deutsche Forschungsgemeinschaft (DFG) [BE4443/6-1, KFO309 P7, SFB CRC1213]
  4. National Key Research and Development Program of China [2016YFC1304000]
  5. DZL

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Adipocytes not only store energy and regulate metabolic processes through adipokines, but also influence insulin resistance and obesity. Lipid-laden lipofibroblasts in the lungs share similarities with adipocytes and may impact alveolar lipid homeostasis, with FGF10 playing key roles in adipocyte and lipofibroblast biology.
Adipocytes not only function as energy depots but also secrete numerous adipokines that regulate multiple metabolic processes, including lipid homeostasis. Dysregulation of lipid homeostasis, which often leads to adipocyte hypertrophy and/or ectopic lipid deposition in non-adipocyte cells such as muscle and liver, is linked to the development of insulin resistance. Similarly, an altered secretion profile of adipokines or imbalance between calorie intake and energy expenditure is associated with obesity, among other related metabolic disorders. In lungs, lipid-laden adipocyte-like cells known as lipofibroblasts share numerous developmental and functional similarities with adipocytes, and similarly influence alveolar lipid homeostasis by facilitating pulmonary surfactant production. Unsurprisingly, disruption in alveolar lipid homeostasis may propagate several chronic inflammatory disorders of the lung. Given the numerous similarities between the two cell types, dissecting the molecular mechanisms underlying adipocyte development and function will offer valuable insights that may be applied to, at least, some aspects of lipofibroblast biology in normal and diseased lungs. FGF10, a major ligand for FGFR2b, is a multifunctional growth factor that is indispensable for several biological processes, including development of various organs and tissues such as the lung and WAT. Moreover, accumulating evidence strongly implicates FGF10 in several key aspects of adipogenesis as well as lipofibroblast formation and maintenance, and as a potential player in adipocyte metabolism. This review summarizes our current understanding of the role of FGF10 in adipocytes, while attempting to derive insights on the existing literature and extrapolate the knowledge to pulmonary lipofibroblasts.

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