2. Academic Validation
  3. Engineering an energy-dissipating hybrid tissue in vivo for obesity treatment

Engineering an energy-dissipating hybrid tissue in vivo for obesity treatment

  • Cell Rep. 2024 Jul 23;43(7):114425. doi: 10.1016/j.celrep.2024.114425.
Lintao Wang 1,  Yajie Sun 2,  Lifang Yang 2,  Shaocong Wang 2,  Chunyan Liu 3,  Yulian Wang 2,  Yiming Niu 4,  Zhen Huang 2,  Junfeng Zhang 5,  Chunming Wang 6,  Lei Dong 7
Affiliations

Affiliations

  • 1 State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 163 Xianlin Avenue, Nanjing 210093, China; School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.
  • 2 State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 163 Xianlin Avenue, Nanjing 210093, China.
  • 3 Medical School, Nanjing University, Nanjing 210093, China.
  • 4 State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau SAR, China.
  • 5 State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 163 Xianlin Avenue, Nanjing 210093, China; School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China; Medical School, Nanjing University, Nanjing 210093, China. Electronic address: jfzhang@nju.edu.cn.
  • 6 State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau SAR, China; Department of Pharmaceutical Sciences, Faculty of Health Science, University of Macau, Taipa, Macau SAR, China. Electronic address: cmwang@umac.mo.
  • 7 State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 163 Xianlin Avenue, Nanjing 210093, China; Chemistry and Biomedicine Innovation Center, Nanjing University, Nanjing 210093, China; National Resource Center for Mutant Mice, Nanjing, Jiangsu 210023, China. Electronic address: leidong@nju.edu.cn.
PMID: 38970789 DOI: 10.1016/j.celrep.2024.114425
Abstract

Obesity is a global health challenge with limited therapeutic solutions. Here, we demonstrate the engineering of an energy-dissipating hybrid tissue (EDHT) in the body for weight control. EDHT is constructed by implanting a synthetic gel matrix comprising immunomodulatory signals and functional cells into the recipient mouse. The immunomodulatory signals induce the host stromal cells to create an immunosuppressive niche that protects the functional cells, which are overexpressing the uncoupling protein 1 (UCP1), from immune rejection. Consequently, these endogenous and exogenous cells co-develop a hybrid tissue that sustainedly produces UCP1 to accelerate the host's energy expenditure. Systematic experiments in high-fat diet (HFD) and transgenic (ob/ob) mice show that EDHT efficiently reduces body weight and relieves obesity-associated pathological conditions. Importantly, an 18-month observation for safety assessment excludes cell leakage from EDHT and reports no adverse physiological responses. Overall, EDHT demonstrates convincing efficacy and safety in controlling body weight.

Keywords

CP: Metabolism; UCP1; artificial organ; diabetes; high-fat diet; obesity; uncoupling.

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