A comparative transcriptomics analysis reveals ethylene glycol derivatives of squalene ameliorate excessive lipogenesis and inflammatory response in 3T3-L1 preadipocytes
Yu Cheng,
Farhana Ferdousi,
Bryan Angelo Foronda,
Tran Ngoc Linh,
Munkhzul Ganbold,
Akira Yada,
Takashi Arimura,
Hiroko Isoda
Affiliations
Yu Cheng
Tsukuba Life Science Innovation Program (T-LSI), Graduate School of Science and Technology, University of Tsukuba, Tsukuba, Japan
Farhana Ferdousi
Tsukuba Life Science Innovation Program (T-LSI), Graduate School of Science and Technology, University of Tsukuba, Tsukuba, Japan; Institute of Life and Environmental Sciences, University of Tsukuba, Japan; Alliance of Research on the Mediterranean and North Africa (ARENA), University of Tsukuba, Tsukuba, Japan
Bryan Angelo Foronda
School of Life and Environmental Sciences, University of Tsukuba, Japan
Tran Ngoc Linh
National Institute of Advanced Industrial Science and Technology (AIST)-University of Tsukuba Open Innovation Laboratory for Food and Medicinal Resource Engineering (FoodMed-OIL), University of Tsukuba, Tsukuba, Japan
Munkhzul Ganbold
National Institute of Advanced Industrial Science and Technology (AIST)-University of Tsukuba Open Innovation Laboratory for Food and Medicinal Resource Engineering (FoodMed-OIL), University of Tsukuba, Tsukuba, Japan
Akira Yada
National Institute of Advanced Industrial Science and Technology (AIST)-University of Tsukuba Open Innovation Laboratory for Food and Medicinal Resource Engineering (FoodMed-OIL), University of Tsukuba, Tsukuba, Japan; Interdisciplinary Research Center for Catalytic Chemistry, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba Central 5, 1-1-1 Higashi, Tsukuba, 305-8565, Japan
Takashi Arimura
National Institute of Advanced Industrial Science and Technology (AIST)-University of Tsukuba Open Innovation Laboratory for Food and Medicinal Resource Engineering (FoodMed-OIL), University of Tsukuba, Tsukuba, Japan
Hiroko Isoda
Tsukuba Life Science Innovation Program (T-LSI), Graduate School of Science and Technology, University of Tsukuba, Tsukuba, Japan; Institute of Life and Environmental Sciences, University of Tsukuba, Japan; Alliance of Research on the Mediterranean and North Africa (ARENA), University of Tsukuba, Tsukuba, Japan; National Institute of Advanced Industrial Science and Technology (AIST)-University of Tsukuba Open Innovation Laboratory for Food and Medicinal Resource Engineering (FoodMed-OIL), University of Tsukuba, Tsukuba, Japan; Corresponding author. Faculty of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Squalene (SQ) is a natural compound with anti-inflammatory, anti-cancer, and anti-oxidant effects, but due to its low solubility, its biological properties have been greatly underestimated. This study aims to explore the differences in gene expression patterns of four newly synthesized amphipathic ethylene glycol (EG) derivatives of SQ by whole-genome transcriptomics analysis using DNA microarray to examine the mRNA expression profile of adipocytes differentiated from 3T3-L1 cells treated with SQ and its EG derivatives. Enrichment analyses of the transcriptional data showed that compared with SQ, its EG derivatives exerted different, in most cases desirable, biological responses. EG derivatives showed increased enrichment of mitochondrial functions, lipid and glucose metabolism, and inflammatory response. Mono-, di-, and tetra-SQ showed higher enrichment of the cellular component-ribosome. Histological staining showed EG derivatives prevented excessive lipid accumulation. Additionally, mitochondrial transcription factors showed upregulation in tetra-SQ-treated cells. Notably, EG derivatives showed better anti-inflammatory effects. Further, gene-disease association analysis predicted substantial improvement in the bioactivities of SQ derivatives in metabolic diseases. Cluster analyses revealed di- and tetra-SQ had more functional similarities than others, reflected in their scanning electron microscopy images; both di- and tetra-SQ self-organized into similar sizes and shapes of vesicles, subsequently improving their cation binding activities. Protein-protein interaction networks further revealed that cation binding activity might explain a major part, if not all, of the differences observed in functional analyses. Altogether, the addition of EG derivatives may improve the biological responses of SQ and thus may enhance its health-promoting potential.
