{"id":{"repo_id":"tdl","oai_identifier":"oai:tdl-ir.tdl.org:2346/104567"},"canonical_url":"https://search.dev.ndltd.org/etd/tdl/oai:tdl-ir.tdl.org:2346/104567","repository":{"repo_id":"tdl","name":"Texas Digital Library","base_url":"https://tdl-ir.tdl.org/server/oai/request"},"display":{"title":"Anti-Obesity Effects of Adipose-Targeting Resveratrol Nanocarriers","abstract":"Obesity is an important public health issue in the United States. When energy intake exceeds expenditure, excess energy is stored in the form of fat in adipose tissue, and weight gain occurs. Since induced brown-like/beige adipocytes have the same thermogenesis and metabolic sink functions as classical brown adipocytes, browning subcutaneous white adipose tissue (WAT) might be a practical and efficient approach for combating obesity. Trans-resveratrol (R) has an anti-obesity potential via inducing adipose stromal stem cells (ASC) differentiation into beige adipocytes in WAT. But its low levels of aqueous solubility, bioavailability, and targeting specificity limit its application in obesity. We have successfully synthesized biocompatible and biodegradable R encapsulated lipid nanocarriers (Rnano), and R encapsulated liposomes (Rlipo) (Chapter IV). The mean particle size of Rnano and Rlipo were 140 nm and 110 nm, respectively, and both nanoencapsulation significantly increased aqueous solubility and enhanced chemical stability of R. Further, as compare to the free form of R, Rnano and Rlipo increased cellular R content in 3T3-L1 cells and dose-dependently induced mRNA expression of uncoupling protein 1 (UCP-1) in 3T3-L1 cells under an isoproterenol (ISO)-stimulated condition. To impart ASC target specificity, we have conjugated ASC-targeting peptide (sequence: GSWKYWFGEGGC) to 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[maleimide(polyethylene glycol)-5000] (DSPE-PEG5000-Maleimide) to form DSPE-PEG5000-Peptide conjugate, which is used to synthesize ligand-coated Rnano (L-Rnano). The ASC-targeting peptide and hydrophilic heads of DSPE and phosphatidylcholine face outward (towards the aqueous environment), and their two fatty acid tails are buried inside the hydrophobic core of the L-Rnano. This peptide has a high binding affinity to ASC’s decorin receptor lacking a glycanation site (ΔDCN). (Chapter V). After optimizing the formulae, Rnano and L-Rnano had about 29% and 22% of R loading capacity and 95% and 96% of R encapsulation efficiency, respectively. Compared to non-targeted Rnano, ASC-targeted L-Rnano had significantly higher binding affinity to and uptake by ΔDCN-transduced 3T3-L1 cells (ΔDCN cells) and higher accumulation in WAT of C57BL/6J mice after intravenous administration. We further determine the ASC target specificity of L-Rnano in ΔDCN cells and WAT-derived ASC in mice (Chapter VI). L-Rnano compared to Rnano had higher binding affinity to and uptake by both ΔDCN cells and isolated mouse primary stromal vascular fraction (SVF). As compared to the free form of R and Rnano, L-Rnano increased cellular R content in both ΔDCN cells and primary SVF. In the animal study, Rnano and L-Rnano were injected into the mice intravenously. L-Rnano compared to Rnano had a lower accumulation in the liver and a higher accumulation in WAT depots, primarily inguinal WAT (I-WAT). WAT-derived ASC were identified as CD34+CD29+CD31-CD45- cells and sorted using flow cytometry. L-Rnano compared to Rnano had 7-fold higher ASC target specificity in I-WAT. The ASC target specificity of L-Rnano to other WAT depots was not as dramatic as it to I-WAT. At last, we determined the anti-obesity effects of L-Rnano in C57BL/6J mice (Chapter VII). Male mice were fed with a high-fat diet (HFD) for 9 weeks. After feeding the HFD for 4 weeks, mice received the intravenous injection of saline, free R, Rnano, L-Rnano (15 mg/kg body weight/day), void nanocarriers (Vnano), or ligand-coated Vnano (L-Vnano) for additional 5 weeks. Mice in the L-Rnano treatment group had the lowest body weight and fat mass, and the highest cold resistance, which were correlated with the lowest I-WAT weight, the highest R content in I-WAT, the smallest adipocytes size, the highest UCP-1 mRNA and protein levels in I-WAT, while no significant differences were found in food intake among all treatment groups. In summary, our ASC-targeted nanocarrier system facilitates targeted delivery of R to subcutaneous ASC, which enhances browning of WAT, and subsequently results in body weight and fat loss. This innovative approach may portend a breakthrough in fighting obesity.","abstract_html":"Obesity is an important public health issue in the United States. When energy intake exceeds expenditure, excess energy is stored in the form of fat in adipose tissue, and weight gain occurs. Since induced brown-like/beige adipocytes have the same thermogenesis and metabolic sink functions as classical brown adipocytes, browning subcutaneous white adipose tissue (WAT) might be a practical and efficient approach for combating obesity. Trans-resveratrol (R) has an anti-obesity potential via inducing adipose stromal stem cells (ASC) differentiation into beige adipocytes in WAT. But its low levels of aqueous solubility, bioavailability, and targeting specificity limit its application in obesity. We have successfully synthesized biocompatible and biodegradable R encapsulated lipid nanocarriers (Rnano), and R encapsulated liposomes (Rlipo) (Chapter IV). The mean particle size of Rnano and Rlipo were 140 nm and 110 nm, respectively, and both nanoencapsulation significantly increased aqueous solubility and enhanced chemical stability of R. Further, as compare to the free form of R, Rnano and Rlipo increased cellular R content in 3T3-L1 cells and dose-dependently induced mRNA expression of uncoupling protein 1 (UCP-1) in 3T3-L1 cells under an isoproterenol (ISO)-stimulated condition. To impart ASC target specificity, we have conjugated ASC-targeting peptide (sequence: GSWKYWFGEGGC) to 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[maleimide(polyethylene glycol)-5000] (DSPE-PEG5000-Maleimide) to form DSPE-PEG5000-Peptide conjugate, which is used to synthesize ligand-coated Rnano (L-Rnano). The ASC-targeting peptide and hydrophilic heads of DSPE and phosphatidylcholine face outward (towards the aqueous environment), and their two fatty acid tails are buried inside the hydrophobic core of the L-Rnano. This peptide has a high binding affinity to ASC’s decorin receptor lacking a glycanation site (ΔDCN). (Chapter V). After optimizing the formulae, Rnano and L-Rnano had about 29% and 22% of R loading capacity and 95% and 96% of R encapsulation efficiency, respectively. Compared to non-targeted Rnano, ASC-targeted L-Rnano had significantly higher binding affinity to and uptake by ΔDCN-transduced 3T3-L1 cells (ΔDCN cells) and higher accumulation in WAT of C57BL/6J mice after intravenous administration. We further determine the ASC target specificity of L-Rnano in ΔDCN cells and WAT-derived ASC in mice (Chapter VI). L-Rnano compared to Rnano had higher binding affinity to and uptake by both ΔDCN cells and isolated mouse primary stromal vascular fraction (SVF). As compared to the free form of R and Rnano, L-Rnano increased cellular R content in both ΔDCN cells and primary SVF. In the animal study, Rnano and L-Rnano were injected into the mice intravenously. L-Rnano compared to Rnano had a lower accumulation in the liver and a higher accumulation in WAT depots, primarily inguinal WAT (I-WAT). WAT-derived ASC were identified as CD34+CD29+CD31-CD45- cells and sorted using flow cytometry. L-Rnano compared to Rnano had 7-fold higher ASC target specificity in I-WAT. The ASC target specificity of L-Rnano to other WAT depots was not as dramatic as it to I-WAT. At last, we determined the anti-obesity effects of L-Rnano in C57BL/6J mice (Chapter VII). Male mice were fed with a high-fat diet (HFD) for 9 weeks. After feeding the HFD for 4 weeks, mice received the intravenous injection of saline, free R, Rnano, L-Rnano (15 mg/kg body weight/day), void nanocarriers (Vnano), or ligand-coated Vnano (L-Vnano) for additional 5 weeks. Mice in the L-Rnano treatment group had the lowest body weight and fat mass, and the highest cold resistance, which were correlated with the lowest I-WAT weight, the highest R content in I-WAT, the smallest adipocytes size, the highest UCP-1 mRNA and protein levels in I-WAT, while no significant differences were found in food intake among all treatment groups. In summary, our ASC-targeted nanocarrier system facilitates targeted delivery of R to subcutaneous ASC, which enhances browning of WAT, and subsequently results in body weight and fat loss. This innovative approach may portend a breakthrough in fighting obesity.","abstract_has_math":false,"creators":["Zu, Yujiao"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Wang, Shu","Moustaid-Moussa, Naima","Dhurandhar, Nikhil","Dufour, Jannette M","Zhao, Ling","Hao, Lei"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2018,"date_issued":"2018-12","date_published":"2018-12","updated_at":"2026-07-27T21:19:19Z","subjects":[],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/2346/104567","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Wang, Shu","Moustaid-Moussa, Naima","Dhurandhar, Nikhil","Dufour, Jannette M","Zhao, Ling","Hao, Lei"]},{"key":"dc:creator","label":"Author","values":["Zu, Yujiao"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2026-02-19T18:58:02Z"]},{"key":"dc:date.issued","label":"Date","values":["2018-12"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://hdl.handle.net/2346/104567"]},{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/2346/104567"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Obesity is an important public health issue in the United States. When energy intake exceeds expenditure, excess energy is stored in the form of fat in adipose tissue, and weight gain occurs. Since induced brown-like/beige adipocytes have the same thermogenesis and metabolic sink functions as classical brown adipocytes, browning subcutaneous white adipose tissue (WAT) might be a practical and efficient approach for combating obesity. Trans-resveratrol (R) has an anti-obesity potential via inducing adipose stromal stem cells (ASC) differentiation into beige adipocytes in WAT. But its low levels of aqueous solubility, bioavailability, and targeting specificity limit its application in obesity. We have successfully synthesized biocompatible and biodegradable R encapsulated lipid nanocarriers (Rnano), and R encapsulated liposomes (Rlipo) (Chapter IV). The mean particle size of Rnano and Rlipo were 140 nm and 110 nm, respectively, and both nanoencapsulation significantly increased aqueous solubility and enhanced chemical stability of R. Further, as compare to the free form of R, Rnano and Rlipo increased cellular R content in 3T3-L1 cells and dose-dependently induced mRNA expression of uncoupling protein 1 (UCP-1) in 3T3-L1 cells under an isoproterenol (ISO)-stimulated condition. To impart ASC target specificity, we have conjugated ASC-targeting peptide (sequence: GSWKYWFGEGGC) to 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[maleimide(polyethylene glycol)-5000] (DSPE-PEG5000-Maleimide) to form DSPE-PEG5000-Peptide conjugate, which is used to synthesize ligand-coated Rnano (L-Rnano). The ASC-targeting peptide and hydrophilic heads of DSPE and phosphatidylcholine face outward (towards the aqueous environment), and their two fatty acid tails are buried inside the hydrophobic core of the L-Rnano. This peptide has a high binding affinity to ASC’s decorin receptor lacking a glycanation site (ΔDCN). (Chapter V). After optimizing the formulae, Rnano and L-Rnano had about 29% and 22% of R loading capacity and 95% and 96% of R encapsulation efficiency, respectively. Compared to non-targeted Rnano, ASC-targeted L-Rnano had significantly higher binding affinity to and uptake by ΔDCN-transduced 3T3-L1 cells (ΔDCN cells) and higher accumulation in WAT of C57BL/6J mice after intravenous administration. We further determine the ASC target specificity of L-Rnano in ΔDCN cells and WAT-derived ASC in mice (Chapter VI). L-Rnano compared to Rnano had higher binding affinity to and uptake by both ΔDCN cells and isolated mouse primary stromal vascular fraction (SVF). As compared to the free form of R and Rnano, L-Rnano increased cellular R content in both ΔDCN cells and primary SVF. In the animal study, Rnano and L-Rnano were injected into the mice intravenously. L-Rnano compared to Rnano had a lower accumulation in the liver and a higher accumulation in WAT depots, primarily inguinal WAT (I-WAT). WAT-derived ASC were identified as CD34+CD29+CD31-CD45- cells and sorted using flow cytometry. L-Rnano compared to Rnano had 7-fold higher ASC target specificity in I-WAT. The ASC target specificity of L-Rnano to other WAT depots was not as dramatic as it to I-WAT. At last, we determined the anti-obesity effects of L-Rnano in C57BL/6J mice (Chapter VII). Male mice were fed with a high-fat diet (HFD) for 9 weeks. After feeding the HFD for 4 weeks, mice received the intravenous injection of saline, free R, Rnano, L-Rnano (15 mg/kg body weight/day), void nanocarriers (Vnano), or ligand-coated Vnano (L-Vnano) for additional 5 weeks. Mice in the L-Rnano treatment group had the lowest body weight and fat mass, and the highest cold resistance, which were correlated with the lowest I-WAT weight, the highest R content in I-WAT, the smallest adipocytes size, the highest UCP-1 mRNA and protein levels in I-WAT, while no significant differences were found in food intake among all treatment groups. In summary, our ASC-targeted nanocarrier system facilitates targeted delivery of R to subcutaneous ASC, which enhances browning of WAT, and subsequently results in body weight and fat loss. This innovative approach may portend a breakthrough in fighting obesity."]},{"key":"dc:title","label":"Title","values":["Anti-Obesity Effects of Adipose-Targeting Resveratrol Nanocarriers"]}]}],"canonical_facts":{"dc:contributor":["Wang, Shu","Moustaid-Moussa, Naima","Dhurandhar, Nikhil","Dufour, Jannette M","Zhao, Ling","Hao, Lei"],"dc:creator":["Zu, Yujiao"],"dc:date.accessioned":["2026-02-19T18:58:02Z"],"dc:date.issued":["2018-12"],"dc:description.abstract":["Obesity is an important public health issue in the United States. When energy intake exceeds expenditure, excess energy is stored in the form of fat in adipose tissue, and weight gain occurs. Since induced brown-like/beige adipocytes have the same thermogenesis and metabolic sink functions as classical brown adipocytes, browning subcutaneous white adipose tissue (WAT) might be a practical and efficient approach for combating obesity. Trans-resveratrol (R) has an anti-obesity potential via inducing adipose stromal stem cells (ASC) differentiation into beige adipocytes in WAT. But its low levels of aqueous solubility, bioavailability, and targeting specificity limit its application in obesity. We have successfully synthesized biocompatible and biodegradable R encapsulated lipid nanocarriers (Rnano), and R encapsulated liposomes (Rlipo) (Chapter IV). The mean particle size of Rnano and Rlipo were 140 nm and 110 nm, respectively, and both nanoencapsulation significantly increased aqueous solubility and enhanced chemical stability of R. Further, as compare to the free form of R, Rnano and Rlipo increased cellular R content in 3T3-L1 cells and dose-dependently induced mRNA expression of uncoupling protein 1 (UCP-1) in 3T3-L1 cells under an isoproterenol (ISO)-stimulated condition. To impart ASC target specificity, we have conjugated ASC-targeting peptide (sequence: GSWKYWFGEGGC) to 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[maleimide(polyethylene glycol)-5000] (DSPE-PEG5000-Maleimide) to form DSPE-PEG5000-Peptide conjugate, which is used to synthesize ligand-coated Rnano (L-Rnano). The ASC-targeting peptide and hydrophilic heads of DSPE and phosphatidylcholine face outward (towards the aqueous environment), and their two fatty acid tails are buried inside the hydrophobic core of the L-Rnano. This peptide has a high binding affinity to ASC’s decorin receptor lacking a glycanation site (ΔDCN). (Chapter V). After optimizing the formulae, Rnano and L-Rnano had about 29% and 22% of R loading capacity and 95% and 96% of R encapsulation efficiency, respectively. Compared to non-targeted Rnano, ASC-targeted L-Rnano had significantly higher binding affinity to and uptake by ΔDCN-transduced 3T3-L1 cells (ΔDCN cells) and higher accumulation in WAT of C57BL/6J mice after intravenous administration. We further determine the ASC target specificity of L-Rnano in ΔDCN cells and WAT-derived ASC in mice (Chapter VI). L-Rnano compared to Rnano had higher binding affinity to and uptake by both ΔDCN cells and isolated mouse primary stromal vascular fraction (SVF). As compared to the free form of R and Rnano, L-Rnano increased cellular R content in both ΔDCN cells and primary SVF. In the animal study, Rnano and L-Rnano were injected into the mice intravenously. L-Rnano compared to Rnano had a lower accumulation in the liver and a higher accumulation in WAT depots, primarily inguinal WAT (I-WAT). WAT-derived ASC were identified as CD34+CD29+CD31-CD45- cells and sorted using flow cytometry. L-Rnano compared to Rnano had 7-fold higher ASC target specificity in I-WAT. The ASC target specificity of L-Rnano to other WAT depots was not as dramatic as it to I-WAT. At last, we determined the anti-obesity effects of L-Rnano in C57BL/6J mice (Chapter VII). Male mice were fed with a high-fat diet (HFD) for 9 weeks. After feeding the HFD for 4 weeks, mice received the intravenous injection of saline, free R, Rnano, L-Rnano (15 mg/kg body weight/day), void nanocarriers (Vnano), or ligand-coated Vnano (L-Vnano) for additional 5 weeks. Mice in the L-Rnano treatment group had the lowest body weight and fat mass, and the highest cold resistance, which were correlated with the lowest I-WAT weight, the highest R content in I-WAT, the smallest adipocytes size, the highest UCP-1 mRNA and protein levels in I-WAT, while no significant differences were found in food intake among all treatment groups. In summary, our ASC-targeted nanocarrier system facilitates targeted delivery of R to subcutaneous ASC, which enhances browning of WAT, and subsequently results in body weight and fat loss. This innovative approach may portend a breakthrough in fighting obesity."],"dc:identifier":["https://hdl.handle.net/2346/104567"],"dc:identifier.uri":["https://hdl.handle.net/2346/104567"],"dc:title":["Anti-Obesity Effects of Adipose-Targeting Resveratrol Nanocarriers"],"dc:type":["Thesis"]},"updated_at":"2026-07-27T21:19:19Z"}