Galectin-3 promotes the adipogenic differentiation of PDGFRα+ cells and ectopic fat formation in regenerating muscle
| Autor: | Naoki Takada, Masaki Takasugi, Yoshiki Nonaka, Tomonori Kamiya, Kazuaki Takemura, Junko Satoh, Shinji Ito, Kosuke Fujimoto, Satoshi Uematsu, Kayo Yoshida, Takashi Morita, Hiroaki Nakamura, Akiyoshi Uezumi, Naoko Ohtani |
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| Rok vydání: | 2021 |
| Předmět: |
Mice
Knockout Adipogenesis Receptor Platelet-Derived Growth Factor alpha Galectin 3 Cell Differentiation Mesenchymal Stem Cells Diet High-Fat Cardiotoxins Actins Mice Inbred C57BL PPAR gamma Mice Adipose Tissue Animals Regeneration Female Obesity Muscle Skeletal Molecular Biology Cellular Senescence Developmental Biology Signal Transduction |
| Zdroj: | Development (Cambridge, England). 149(3) |
| ISSN: | 1477-9129 |
| Popis: | Worldwide prevalence of obesity is associated with the increase of lifestyle-related diseases. The accumulation of intermuscular adipose tissue (IMAT) is considered a major problem whereby obesity leads to sarcopenia and metabolic disorders and thus is a promising target for treating these pathological conditions. However, whereas obesity-associated IMAT is suggested to originate from PDGFRα+ mesenchymal progenitors, the processes underlying this adipogenesis remain largely unexplored. Here, we comprehensively investigated intra- and extracellular changes associated with these processes using single-cell RNA sequencing and mass spectrometry. Our single-cell RNA sequencing analysis identified a small PDGFRα+ cell population in obese mice directed strongly toward adipogenesis. Proteomic analysis showed that the appearance of this cell population is accompanied by an increase in galectin-3 in interstitial environments, which was found to activate adipogenic PPARγ signals in PDGFRα+ cells. Moreover, IMAT formation during muscle regeneration was significantly suppressed in galectin-3 knockout mice. Our findings, together with these multi-omics datasets, could unravel microenvironmental networks during muscle regeneration highlighting possible therapeutic targets against IMAT formation in obesity. |
| Databáze: | OpenAIRE |
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