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- Title
Adipocyte-Targeted Nanocomplex with Synergistic Photothermal and Pharmacological Effects for Combating Obesity and Related Metabolic Syndromes.
- Authors
Zhang, Yuanyuan; Zeng, Xiaojiao; Wu, Fan; Yang, Xiaopeng; Che, Tingting; Zheng, Yin; Li, Jie; Zhang, Yufei; Zhang, Xinge; Wu, Zhongming
- Abstract
Obesity is a global epidemic which induces a multitude of metabolic disorders. Browning of white adipose tissue (WAT) has emerged as a promising therapeutic strategy for promoting weight loss and improving associated metabolic syndromes in people with obesity. However, current methods of inducing white adipose tissue browning have limited applicability. We developed a nanocomplex pTSL@(P+I), which is a temperature-sensitive liposome (TSL) surface-conjugated with an adipocyte-targeting peptide (p) and loaded with both browning-promoting agents (P) and photosensitizing agents (I). This nanocomplex exhibits adipocyte targeting, as well as synergistic pharmacological and photothermal properties to promote browning. pTSL@(P+I) effectively upregulates UCP1 and COX5B expression by activating the transcription axis of PPARγ/PGC1α and HSF1/PGC1α, thereby promoting white adipose tissue browning and reducing obesity. This novel nanocomplex exhibited a uniform spherical shape, with an average diameter of approximately 200 nm. Additionally, the nanocomplexes exhibited remarkable photothermal properties and biocompatibility. Further, when adipocytes were treated with pTSL@(P+I), their triglyceride content decreased remarkably and intracellular mitochondrial activity increased significantly. When applied to diet-induced obesity (DIO) mice, the nanocomplex exhibited significant efficacy, demonstrating a notable 14.4% reduction in body weight from the initial measurement, a decreased fat/lean mass ratio of 20.8%, and no statistically significant disparities (p > 0.05) in associated side effects when compared to the control group. In summary, implementation of the targeted nanocomplex pTSL@(P+I) to enhance energy expenditure by stimulating white adipose tissue browning offers a promising therapeutic approach for the treatment of obesity and related metabolic syndromes.
- Subjects
WEIGHT loss; WHITE adipose tissue; BROWN adipose tissue; LEAN body mass; METABOLIC syndrome; ADIPOSE tissues
- Publication
Nanomaterials (2079-4991), 2024, Vol 14, Issue 16, p1363
- ISSN
2079-4991
- Publication type
Article
- DOI
10.3390/nano14161363