Nanoparticle-Mediated Inhibition of Notch Signaling Promotes Mitochondrial Biogenesis and Reduces Subcutaneous Adipose Tissue Expansion in Pigs
Summary: Inhibition of Notch signaling has been shown to induce white to beige transformation of adipocytes and reduce the risk of obesity in mice. However, it remains unknown whether the metabolic benefits of Notch inhibition are dependent on uncoupling protein 1 (UCP1)-mediated thermogenesis and e...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-06-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004220303527 |
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| author | Di Huang Naagarajan Narayanan Mario A. Cano-Vega Zhihao Jia Kolapo M. Ajuwon Shihuan Kuang Meng Deng |
| author_facet | Di Huang Naagarajan Narayanan Mario A. Cano-Vega Zhihao Jia Kolapo M. Ajuwon Shihuan Kuang Meng Deng |
| author_sort | Di Huang |
| collection | DOAJ |
| description | Summary: Inhibition of Notch signaling has been shown to induce white to beige transformation of adipocytes and reduce the risk of obesity in mice. However, it remains unknown whether the metabolic benefits of Notch inhibition are dependent on uncoupling protein 1 (UCP1)-mediated thermogenesis and evolutionarily relevant in other mammalian species. Here we report the effect of Notch inhibition in adipocytes of pigs, which lost the UCP1 gene during evolution. Notch inhibition using a γ-secretase inhibitor dibenzazepine (DBZ) promoted beige adipogenesis and mitochondrial biogenic gene expression in porcine adipocytes. Moreover, encapsulation of DBZ into poly(lactide-co-glycolide) nanoparticles enabled rapid cellular internalization and enhanced bioactivity to achieve sustained Notch inhibition, thereby inducing beige-specific gene expression and reducing subcutaneous adipose tissue expansion in pigs. These results demonstrate for the first time a role of Notch signaling in regulating adipose plasticity in large animals, highlighting the therapeutic potential of targeting Notch signaling in obesity treatment. |
| first_indexed | 2024-12-23T20:46:32Z |
| format | Article |
| id | doaj.art-4e35d8073b7740439097310b39f6ff67 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-23T20:46:32Z |
| publishDate | 2020-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-4e35d8073b7740439097310b39f6ff672022-12-21T17:31:46ZengElsevieriScience2589-00422020-06-01236101167Nanoparticle-Mediated Inhibition of Notch Signaling Promotes Mitochondrial Biogenesis and Reduces Subcutaneous Adipose Tissue Expansion in PigsDi Huang0Naagarajan Narayanan1Mario A. Cano-Vega2Zhihao Jia3Kolapo M. Ajuwon4Shihuan Kuang5Meng Deng6Department of Animal Sciences, Purdue University, West Lafayette, IN 47907, USA; Department of Agricultural and Biological Engineering, Purdue University, West Lafayette, IN 47907, USA; Bindley Bioscience Center, Purdue University, West Lafayette, IN 47907, USADepartment of Agricultural and Biological Engineering, Purdue University, West Lafayette, IN 47907, USA; Bindley Bioscience Center, Purdue University, West Lafayette, IN 47907, USADepartment of Agricultural and Biological Engineering, Purdue University, West Lafayette, IN 47907, USA; Bindley Bioscience Center, Purdue University, West Lafayette, IN 47907, USADepartment of Animal Sciences, Purdue University, West Lafayette, IN 47907, USADepartment of Animal Sciences, Purdue University, West Lafayette, IN 47907, USADepartment of Animal Sciences, Purdue University, West Lafayette, IN 47907, USA; Center for Cancer Research, Purdue University, West Lafayette, IN 47907, USA; Corresponding authorDepartment of Agricultural and Biological Engineering, Purdue University, West Lafayette, IN 47907, USA; Bindley Bioscience Center, Purdue University, West Lafayette, IN 47907, USA; School of Materials Engineering, Purdue University, West Lafayette, IN 47907, USA; Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA; Corresponding authorSummary: Inhibition of Notch signaling has been shown to induce white to beige transformation of adipocytes and reduce the risk of obesity in mice. However, it remains unknown whether the metabolic benefits of Notch inhibition are dependent on uncoupling protein 1 (UCP1)-mediated thermogenesis and evolutionarily relevant in other mammalian species. Here we report the effect of Notch inhibition in adipocytes of pigs, which lost the UCP1 gene during evolution. Notch inhibition using a γ-secretase inhibitor dibenzazepine (DBZ) promoted beige adipogenesis and mitochondrial biogenic gene expression in porcine adipocytes. Moreover, encapsulation of DBZ into poly(lactide-co-glycolide) nanoparticles enabled rapid cellular internalization and enhanced bioactivity to achieve sustained Notch inhibition, thereby inducing beige-specific gene expression and reducing subcutaneous adipose tissue expansion in pigs. These results demonstrate for the first time a role of Notch signaling in regulating adipose plasticity in large animals, highlighting the therapeutic potential of targeting Notch signaling in obesity treatment.http://www.sciencedirect.com/science/article/pii/S2589004220303527Biological SciencesPhysiologyCellular PhysiologyCell Biology |
| spellingShingle | Di Huang Naagarajan Narayanan Mario A. Cano-Vega Zhihao Jia Kolapo M. Ajuwon Shihuan Kuang Meng Deng Nanoparticle-Mediated Inhibition of Notch Signaling Promotes Mitochondrial Biogenesis and Reduces Subcutaneous Adipose Tissue Expansion in Pigs iScience Biological Sciences Physiology Cellular Physiology Cell Biology |
| title | Nanoparticle-Mediated Inhibition of Notch Signaling Promotes Mitochondrial Biogenesis and Reduces Subcutaneous Adipose Tissue Expansion in Pigs |
| title_full | Nanoparticle-Mediated Inhibition of Notch Signaling Promotes Mitochondrial Biogenesis and Reduces Subcutaneous Adipose Tissue Expansion in Pigs |
| title_fullStr | Nanoparticle-Mediated Inhibition of Notch Signaling Promotes Mitochondrial Biogenesis and Reduces Subcutaneous Adipose Tissue Expansion in Pigs |
| title_full_unstemmed | Nanoparticle-Mediated Inhibition of Notch Signaling Promotes Mitochondrial Biogenesis and Reduces Subcutaneous Adipose Tissue Expansion in Pigs |
| title_short | Nanoparticle-Mediated Inhibition of Notch Signaling Promotes Mitochondrial Biogenesis and Reduces Subcutaneous Adipose Tissue Expansion in Pigs |
| title_sort | nanoparticle mediated inhibition of notch signaling promotes mitochondrial biogenesis and reduces subcutaneous adipose tissue expansion in pigs |
| topic | Biological Sciences Physiology Cellular Physiology Cell Biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004220303527 |
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