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

• Published in: Nature communications Vol. 15; no. 1; p. 72
• Main Authors: Lu, Yichao, Luo, Zhenyu, Zhou, Huanli, Shi, Yingying, Zhu, Ying, Guo, Xuemeng, Huang, Jiaxin, Zhang, Junlei, Liu, Xu, Wang, Sijie, Shan, Xinyu, Yin, Hang, Du, Yongzhong, Li, Qingpo, You, Jian, Luo, Lihua
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 02.01.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 13/1; 14; 14/1; 14/34; 59; 631/154; 64/60; 692/499; 692/699; Activating transcription factor 1; Adipocytes; Adipose tissue; Adipose Tissue - metabolism; Adiposity; Animals; Body fat; Central nervous system; Diet, High-Fat - adverse effects; Droplets; Effectiveness; Emulsions; Endoplasmic reticulum; Enlargement; Fatty liver; Female; Females; Gastrointestinal system; Gastrointestinal tract; Humanities and Social Sciences; Hyperplasia; Hyperplasia - metabolism; Hypertrophy; Hypertrophy - pathology; Inhibitors; Lipids; Liver diseases; Mice; multidisciplinary; Nanoemulsions; Obesity; Obesity - metabolism; Oxidative stress; Reactive oxygen species; Science; Science (multidisciplinary); Side effects; Tissue Distribution; Tocopherol
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-44416-3

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. Adipose tissue enlargement involves adipose hyperplasia and hypertrophy, which correlate with excessive ROS and hyperactivated XBP1. Here, the authors introduce KT-NE, a nanoemulsion combining KIRA6 (an XBP1 inhibitor) and α-Tocopherol, easing ER and oxidative stress in (pre)adipocytes and showing anti-obesity effectiveness.