Preventing diet-induced obesity in mice by adipose tissue transformation and angiogenesis using targeted nanoparticles
The incidence of obesity, which is recognized by the American Medical Association as a disease, has nearly doubled since 1980, and obesity-related comorbidities have become a major threat to human health. Given that adipose tissue expansion and transformation require active growth of new blood vascu...
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| Format: | Article |
| Language: | en_US |
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National Academy of Sciences (U.S.)
2016
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| Online Access: | http://hdl.handle.net/1721.1/105741 https://orcid.org/0000-0002-1634-3329 https://orcid.org/0000-0003-4255-0492 |
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| author | Zhang, Xue-Qing Farokhzad, Omid C. Xu, Xiaoyang Xue, Yuan Langer, Robert S |
| author2 | Massachusetts Institute of Technology. Department of Chemical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Chemical Engineering Zhang, Xue-Qing Farokhzad, Omid C. Xu, Xiaoyang Xue, Yuan Langer, Robert S |
| author_sort | Zhang, Xue-Qing |
| collection | MIT |
| description | The incidence of obesity, which is recognized by the American Medical Association as a disease, has nearly doubled since 1980, and obesity-related comorbidities have become a major threat to human health. Given that adipose tissue expansion and transformation require active growth of new blood vasculature, angiogenesis offers a potential target for the treatment of obesity-associated disorders. Here we construct two peptide-functionalized nanoparticle (NP) platforms to deliver either Peroxisome Proliferator-Activated Receptor gamma (PPARgamma) activator rosiglitazone (Rosi) or prostaglandin E2 analog (16,16-dimethyl PGE2) to adipose tissue vasculature. These NPs were engineered through self-assembly of a biodegradable triblock polymer composed of end-to-end linkages between poly(lactic-coglycolic acid)-b-poly(ethylene glycol) (PLGA-b-PEG) and an endothelial-targeted peptide. In this system, released Rosi promotes both transformation of white adipose tissue (WAT) into brown-like adipose tissue and angiogenesis, which facilitates the homing of targeted NPs to adipose angiogenic vessels, thereby amplifying their delivery. We show that i.v. administration of these NPs can target WAT vasculature, stimulate the angiogenesis that is required for the transformation of adipose tissue, and transform WAT into brown-like adipose tissue, by the up-regulation of angiogenesis and brown adipose tissue markers. In a diet-induced obese mouse model, these angiogenesis-targeted NPs have inhibited body weight gain and modulated several serological markers including cholesterol, triglyceride, and insulin, compared with the control group. These findings suggest that angiogenesis-targeting moieties with angiogenic stimulator-loaded NPs could be incorporated into effective therapeutic regimens for clinical treatment of obesity and other metabolic diseases. |
| first_indexed | 2024-09-23T11:13:46Z |
| format | Article |
| id | mit-1721.1/105741 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:13:46Z |
| publishDate | 2016 |
| publisher | National Academy of Sciences (U.S.) |
| record_format | dspace |
| spelling | mit-1721.1/1057412022-09-27T18:02:01Z Preventing diet-induced obesity in mice by adipose tissue transformation and angiogenesis using targeted nanoparticles Zhang, Xue-Qing Farokhzad, Omid C. Xu, Xiaoyang Xue, Yuan Langer, Robert S Massachusetts Institute of Technology. Department of Chemical Engineering Koch Institute for Integrative Cancer Research at MIT Xu, Xiaoyang Xue, Yuan Langer, Robert S The incidence of obesity, which is recognized by the American Medical Association as a disease, has nearly doubled since 1980, and obesity-related comorbidities have become a major threat to human health. Given that adipose tissue expansion and transformation require active growth of new blood vasculature, angiogenesis offers a potential target for the treatment of obesity-associated disorders. Here we construct two peptide-functionalized nanoparticle (NP) platforms to deliver either Peroxisome Proliferator-Activated Receptor gamma (PPARgamma) activator rosiglitazone (Rosi) or prostaglandin E2 analog (16,16-dimethyl PGE2) to adipose tissue vasculature. These NPs were engineered through self-assembly of a biodegradable triblock polymer composed of end-to-end linkages between poly(lactic-coglycolic acid)-b-poly(ethylene glycol) (PLGA-b-PEG) and an endothelial-targeted peptide. In this system, released Rosi promotes both transformation of white adipose tissue (WAT) into brown-like adipose tissue and angiogenesis, which facilitates the homing of targeted NPs to adipose angiogenic vessels, thereby amplifying their delivery. We show that i.v. administration of these NPs can target WAT vasculature, stimulate the angiogenesis that is required for the transformation of adipose tissue, and transform WAT into brown-like adipose tissue, by the up-regulation of angiogenesis and brown adipose tissue markers. In a diet-induced obese mouse model, these angiogenesis-targeted NPs have inhibited body weight gain and modulated several serological markers including cholesterol, triglyceride, and insulin, compared with the control group. These findings suggest that angiogenesis-targeting moieties with angiogenic stimulator-loaded NPs could be incorporated into effective therapeutic regimens for clinical treatment of obesity and other metabolic diseases. National Institutes of Health (U.S.) (Grants EB016101-01A1 and EB006365) Prostate Cancer Foundation (Award in Nanotherapeutics) Swedish Research Council National Institutes of Health (U.S.) (National Research Service Award 1F32CA168163-03) 2016-12-07T19:26:54Z 2016-12-07T19:26:54Z 2016-05 2016-03 Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 http://hdl.handle.net/1721.1/105741 Xue, Yuan et al. “Preventing Diet-Induced Obesity in Mice by Adipose Tissue Transformation and Angiogenesis Using Targeted Nanoparticles.” Proceedings of the National Academy of Sciences 113.20 (2016): 5552–5557. © 2016 National Academy of Sciences https://orcid.org/0000-0002-1634-3329 https://orcid.org/0000-0003-4255-0492 en_US http://dx.doi.org/10.1073/pnas.1603840113 Proceedings of the National Academy of Sciences Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf National Academy of Sciences (U.S.) PNAS |
| spellingShingle | Zhang, Xue-Qing Farokhzad, Omid C. Xu, Xiaoyang Xue, Yuan Langer, Robert S Preventing diet-induced obesity in mice by adipose tissue transformation and angiogenesis using targeted nanoparticles |
| title | Preventing diet-induced obesity in mice by adipose tissue transformation and angiogenesis using targeted nanoparticles |
| title_full | Preventing diet-induced obesity in mice by adipose tissue transformation and angiogenesis using targeted nanoparticles |
| title_fullStr | Preventing diet-induced obesity in mice by adipose tissue transformation and angiogenesis using targeted nanoparticles |
| title_full_unstemmed | Preventing diet-induced obesity in mice by adipose tissue transformation and angiogenesis using targeted nanoparticles |
| title_short | Preventing diet-induced obesity in mice by adipose tissue transformation and angiogenesis using targeted nanoparticles |
| title_sort | preventing diet induced obesity in mice by adipose tissue transformation and angiogenesis using targeted nanoparticles |
| url | http://hdl.handle.net/1721.1/105741 https://orcid.org/0000-0002-1634-3329 https://orcid.org/0000-0003-4255-0492 |
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