A diethylene glycol oligomer squalene derivative modulates metabolic gene expression in ob/ob mice

Authors

  • Yu Cheng Tsukuba Life Science Innovation (T-LSI) Program, Graduate School of Science and Technology, University of Tsukuba, Tsukuba 305-8577, Japan https://orcid.org/0009-0000-8736-8999
  • Munkhzul Ganbold Alliance for Research on the Mediterranean and North Africa (ARENA), University of Tsukuba, Tsukuba 305-8577, Japan https://orcid.org/0000-0002-1810-804X
  • Elda Nurafnie Binti Ibnu Rasid Tsukuba Life Science Innovation (T-LSI) Program, Graduate School of Science and Technology, University of Tsukuba, Tsukuba 305-8577, Japan https://orcid.org/0000-0002-3570-1208
  • Farhana Ferdousi Tsukuba Life Science Innovation (T-LSI) Program, Graduate School of Science and Technology, University of Tsukuba, Tsukuba 305-8577, Japan; Alliance for Research on the Mediterranean and North Africa (ARENA), University of Tsukuba, Tsukuba 305-8577, Japan; Institute of Life and Environmental Sciences, University of Tsukuba, Tsukuba 305-8577, Japan https://orcid.org/0000-0003-2816-9118
  • Hiroko Isoda Institute of Life and Environmental Sciences, University of Tsukuba, Cooperative Research Building A302, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8572, Japan; Tel: 029-853-3982; Fax: 029-853-5776; E-mail: isoda.hiroko.ga@u.tsukuba.ac.jp https://orcid.org/0000-0002-1399-9541

DOI:

https://doi.org/10.17179/excli2026-9373

Keywords:

squalene, obesity, metabolism, ob/ob mice, mitochondrial function, insulin resistance, transcriptomics, DNA microarray

Abstract

Obesity-related metabolic dysregulation is widespread and often leads to complications such as liver dysfunction. Squalene has long been studied for its potential anti-obesity effects due to its role in lipid metabolism, oxidative stress reduction, and inflammation modulation. However, squalene’s hydrophobic nature has limited its applicability in humans. Recently, an amphiphilic form of squalene, namely diethylene glycol oligomer squalene (di-SQ), has shown promise in improving metabolic functions in preadipocytes. However, the in vivo effects and molecular correlates of di-SQ in obesity remain insufficiently characterized. This study aimed to investigate the metabolic effects of di-SQ in an obese mouse model and to explore transcriptomic changes associated with its administration. Using the leptin-deficient ob/ob mouse model, the study employed microarray analysis, histological examination, and real-time PCR to evaluate the impact of di-SQ on obesity and associated metabolic disturbances. Di-SQ reduced body weight gain without affecting food intake and alleviated hepatic steatosis and epididymal white adipose tissue (eWAT) lipid accumulation in ob/ob mice. In the liver, di-SQ was associated with changes in lipid- and glucose-metabolism-related gene expression, energy balance, and inflammation, potentially involving hepatic Sirt1 and Prkaa1 expression. In eWAT, di-SQ was associated with reduced lipid accumulation, altered lipid-metabolism- and thermogenesis-related gene expression, and suppressed inflammation, thereby suggesting gene expression patterns consistent with improved insulin signaling. Di-SQ was associated with amelioration of hepatic metabolic dysfunction in ob/ob mice, potentially involving Sirt1 and Prkaa1, and showed gene expression patterns consistent with enhanced insulin signaling. These findings support its potential as a novel bioactive molecule derived from natural products for obesity-related metabolic dysregulation.

Published

2026-09-07

How to Cite

Cheng, Y., Ganbold, M., Binti Ibnu Rasid, E. N., Ferdousi, F., & Isoda, H. (2026). A diethylene glycol oligomer squalene derivative modulates metabolic gene expression in ob/ob mice. EXCLI Journal, 25, 1460–1485. https://doi.org/10.17179/excli2026-9373

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