2. Academic Validation
  3. A nanoemulsion targeting adipose hypertrophy and hyperplasia shows anti-obesity efficiency in female mice

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

  • Nat Commun. 2024 Jan 2;15(1):72. doi: 10.1038/s41467-023-44416-3.
Yichao Lu # 1,  Zhenyu Luo # 1,  Huanli Zhou 1,  Yingying Shi 1,  Ying Zhu 1,  Xuemeng Guo 1,  Jiaxin Huang 1,  Junlei Zhang 1,  Xu Liu 1,  Sijie Wang 1,  Xinyu Shan 1,  Hang Yin 1,  Yongzhong Du 1,  Qingpo Li 2,  Jian You 3 4 5 6,  Lihua Luo 7
Affiliations

Affiliations

  • 1 College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, Zhejiang, 310058, PR China.
  • 2 College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, Zhejiang, 310058, PR China. liqingpo@zju.edu.cn.
  • 3 College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, Zhejiang, 310058, PR China. youjiandoc@zju.edu.cn.
  • 4 State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, 79 Qingchun Road, Shangcheng District, Hangzhou, Zhejiang, 310006, PR China. youjiandoc@zju.edu.cn.
  • 5 The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 QingChun Road, Hangzhou, Zhejiang, 310000, PR China. youjiandoc@zju.edu.cn.
  • 6 Jinhua Institute of Zhejiang University, 498 Yiwu Street, Jinhua, Zhejiang, 321299, PR China. youjiandoc@zju.edu.cn.
  • 7 College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, Zhejiang, 310058, PR China. luolihua@zju.edu.cn.
  • # Contributed equally.
PMID: 38167723 DOI: 10.1038/s41467-023-44416-3
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.

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