Role of the Wnt/β-Catenin Signaling Pathway in Reducing Lipogenesis of Obese Rats Under Hypoxic Exercise

Abstract

Hypoxic exercise exerts a significant effect on body weight loss and body fat reduction. Methods: In the present study, we constructed an obese rat model and divided rats into the following groups: Normoxic quiet (C), Hypoxic quiet (H), Normoxic Exercise (CE), and Hypoxic Exercise (HE). We employed isobaric tags for relative and absolute quantification (iTRAQ) using proteomic technology to screen the differentially expressed proteins in the four groups. Additionally, we used Reduced-Representation Bisulfite Sequencing (RRBS) to analyze high-throughput DNA methylation profiles in both HE and CE groups. Finally, we screened and analyzed the CpG islands and Differentially Methylated Regions (DMRs) of genes related to the Wnt/β-catenin-signaling pathway. Results: The mRNA levels of gene products related to the Wnt/β-catenin-signaling pathway (i.e., c-myc and β-catenin) were significantly augmented (P<0.05) in the HE group compared to the CE group; the levels of APC and GSK3β were significantly diminished (P<0.05). The expression levels of the Wnt/β-catenin-signaling pathway proteins c-myc and β-catenin were also significantly increased in the HE group relative to the CE group (P<0.05). Among genes related to the Wnt-signaling pathway, the CpG-promoter methylation sites included Fzd2, Fzd9, Wnt16, Wnt2b, Sfrp2, Sfrp1, Sox2, and Sox1; the DMRs included CDC, Fzd10, Gsk-3β, PI3k, Wnt16 and Wnt6. Conclusions: Our present findings provide evidence that hypoxic exercise may inhibit adipogenesis and adipogenesis through canonical Wnt signaling.