A nanoemulsion targeting adipose hypertrophy and hyperplasia shows anti-obesity efficiency in female mice

Yichao Lu, Zhenyu Luo, Huanli Zhou, Yingying Shi, Ying Zhu, Xuemeng Guo, Jiaxin Huang, Junlei Zhang, Xu Liu, Sijie Wang, Xinyu Shan, Hang Yin, Yongzhong Du, Qingpo Li (), Jian You () and Lihua Luo ()
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Yichao Lu: Zhejiang University
Zhenyu Luo: Zhejiang University
Huanli Zhou: Zhejiang University
Yingying Shi: Zhejiang University
Ying Zhu: Zhejiang University
Xuemeng Guo: Zhejiang University
Jiaxin Huang: Zhejiang University
Junlei Zhang: Zhejiang University
Xu Liu: Zhejiang University
Sijie Wang: Zhejiang University
Xinyu Shan: Zhejiang University
Hang Yin: Zhejiang University
Yongzhong Du: Zhejiang University
Qingpo Li: Zhejiang University
Jian You: Zhejiang University
Lihua Luo: Zhejiang University

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: Abstract Obesity often leads to severe medical complications. However, existing FDA-approved medications to combat obesity have limited effectiveness in reducing adiposity and often cause side effects. These medications primarily act on the central nervous system or disrupt fat absorption through the gastrointestinal tract. Adipose tissue enlargement involves adipose hyperplasia and hypertrophy, both of which correlate with increased reactive oxygen species (ROS) and hyperactivated X-box binding protein 1 (XBP1) in (pre)adipocytes. In this study, we demonstrate that KT-NE, a nanoemulsion loaded with the XBP1 inhibitor KIRA6 and α-Tocopherol, simultaneously alleviates aberrant endoplasmic reticulum stress and oxidative stress in (pre)adipocytes. As a result, KT-NE significantly inhibits abnormal adipogenic differentiation, reduces lipid droplet accumulation, restricts lipid droplet transfer, impedes obesity progression, and lowers the risk of obesity-associated non-alcoholic fatty liver disease in female mice with obesity. Furthermore, diverse administration routes of KT-NE impact its in vivo biodistribution and contribute to localized and/or systemic anti-obesity effectiveness.

Date: 2024
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DOI: 10.1038/s41467-023-44416-3

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