Nanoparticle-Mediated Inhibition of Notch Signaling Promotes Mitochondrial Biogenesis and Reduces Subcutaneous Adipose Tissue Expansion in Pigs

Di Huang; Naagarajan Narayanan; Mario A. Cano-Vega; Zhihao Jia; Kolapo M. Ajuwon; Shihuan Kuang; Meng Deng

iScience (Jun 2020)

Nanoparticle-Mediated Inhibition of Notch Signaling Promotes Mitochondrial Biogenesis and Reduces Subcutaneous Adipose Tissue Expansion in Pigs

Di Huang,
Naagarajan Narayanan,
Mario A. Cano-Vega,
Zhihao Jia,
Kolapo M. Ajuwon,
Shihuan Kuang,
Meng Deng

Affiliations

Di Huang: Department of Animal Sciences, Purdue University, West Lafayette, IN 47907, USA; Department of Agricultural and Biological Engineering, Purdue University, West Lafayette, IN 47907, USA; Bindley Bioscience Center, Purdue University, West Lafayette, IN 47907, USA
Naagarajan Narayanan: Department of Agricultural and Biological Engineering, Purdue University, West Lafayette, IN 47907, USA; Bindley Bioscience Center, Purdue University, West Lafayette, IN 47907, USA
Mario A. Cano-Vega: Department of Agricultural and Biological Engineering, Purdue University, West Lafayette, IN 47907, USA; Bindley Bioscience Center, Purdue University, West Lafayette, IN 47907, USA
Zhihao Jia: Department of Animal Sciences, Purdue University, West Lafayette, IN 47907, USA
Kolapo M. Ajuwon: Department of Animal Sciences, Purdue University, West Lafayette, IN 47907, USA
Shihuan Kuang: Department of Animal Sciences, Purdue University, West Lafayette, IN 47907, USA; Center for Cancer Research, Purdue University, West Lafayette, IN 47907, USA; Corresponding author
Meng Deng: Department of Agricultural and Biological Engineering, Purdue University, West Lafayette, IN 47907, USA; Bindley Bioscience Center, Purdue University, West Lafayette, IN 47907, USA; School of Materials Engineering, Purdue University, West Lafayette, IN 47907, USA; Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA; Corresponding author

Journal volume & issue: Vol. 23, no. 6
p. 101167

Abstract

Read online

Summary: Inhibition of Notch signaling has been shown to induce white to beige transformation of adipocytes and reduce the risk of obesity in mice. However, it remains unknown whether the metabolic benefits of Notch inhibition are dependent on uncoupling protein 1 (UCP1)-mediated thermogenesis and evolutionarily relevant in other mammalian species. Here we report the effect of Notch inhibition in adipocytes of pigs, which lost the UCP1 gene during evolution. Notch inhibition using a γ-secretase inhibitor dibenzazepine (DBZ) promoted beige adipogenesis and mitochondrial biogenic gene expression in porcine adipocytes. Moreover, encapsulation of DBZ into poly(lactide-co-glycolide) nanoparticles enabled rapid cellular internalization and enhanced bioactivity to achieve sustained Notch inhibition, thereby inducing beige-specific gene expression and reducing subcutaneous adipose tissue expansion in pigs. These results demonstrate for the first time a role of Notch signaling in regulating adipose plasticity in large animals, highlighting the therapeutic potential of targeting Notch signaling in obesity treatment.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

About the journal

Abstract

Keywords