Facile adipocyte uptake and liver/adipose tissue delivery of conjugated linoleic acid-loaded tocol nanocarriers for a synergistic anti-adipogenesis effect

Ching Yun Hsu, Chia Chih Liao, Zih Chan Lin, Ahmed Alalaiwe, Erica Hwang, Tzu Wei Lin, Jia You Fang*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

Abstract

Obesity is a major risk to human health. Adipogenesis is blocked by α-tocopherol and conjugated linoleic acid (CLA). However, their effect at preventing obesity is uncertain. The effectiveness of the bioactive agents is associated with their delivery method. Herein, we designed CLA-loaded tocol nanostructured lipid carriers (NLCs) for enhancing the anti-adipogenic activity of α-tocopherol and CLA. Adipogenesis inhibition by the nanocarriers was examined using an in vitro adipocyte model and an in vivo rat model fed a high fat diet (HFD). The targeting of the tocol NLCs into adipocytes and adipose tissues were also investigated. A synergistic anti-adipogenesis effect was observed for the combination of free α-tocopherol and CLA. Nanoparticles with different amounts of solid lipid were developed with an average size of 121‒151 nm. The NLCs with the smallest size (121 nm) showed greater adipocyte internalization and differentiation prevention than the larger size. The small-sized NLCs promoted CLA delivery into adipocytes by 5.5-fold as compared to free control. The nanocarriers reduced fat accumulation in adipocytes by counteracting the expression of the adipogenic transcription factors peroxisome proliferator activated receptor (PPAR)γ and CCAAT/enhancer-binding protein (C/EBP)α, and lipogenic enzymes acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS). Localized administration of CLA-loaded tocol NLCs significantly reduced body weight, total cholesterol, and liver damage indicators in obese rats. The biodistribution study demonstrated that the nanoparticles mainly accumulated in liver and adipose tissues. The NLCs decreased adipocyte hypertrophy and cytokine overexpression in the groin and epididymis to a greater degree than the combination of free α-tocopherol and CLA. In conclusion, the lipid-based nanocarriers were verified to inhibit adipogenesis in an efficient and safe way.

Original languageEnglish
Article number50
Pages (from-to)50
JournalJournal of Nanobiotechnology
Volume22
Issue number1
DOIs
StatePublished - 06 02 2024

Bibliographical note

© 2024. The Author(s).

Keywords

  • Anti-adipogenesis
  • Conjugated linoleic acid
  • Nanostructured lipid carriers
  • Obesity
  • Passive targeting
  • α-tocopherol
  • Humans
  • Adipocytes/metabolism
  • Rats
  • Male
  • Obesity/metabolism
  • Tissue Distribution
  • alpha-Tocopherol/metabolism
  • Animals
  • Adipose Tissue/metabolism
  • Liver/metabolism
  • Linoleic Acids, Conjugated/pharmacology
  • Tocopherols
  • Adipogenesis

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