Regulation of De Novo Lipid Synthesis by the Small GTPase Rac1 in the Adipogenic Differentiation of Progenitor Cells from Mouse White Adipose Tissue

• Published in: International journal of molecular sciences 2023-02, Vol.24 (5), p.4608
• Main Authors: Hasegawa, Kiko, Takenaka, Nobuyuki, Yamamoto, Maaya, Sakoda, Yoshiki, Aiba, Atsu, Satoh, Takaya
• Format: Article
• Language: English
• Subjects: 3T3-L1 Cells; Adipocytes; Adipogenesis; adipogenic differentiation; adipose progenitor cell; Adipose tissue; Adipose Tissue - metabolism; Adipose Tissue, White - metabolism; Adipose tissues; Animals; Atrophy; Body fat; C/EBPα; CCAAT/enhancer-binding protein; Cell Differentiation; Cells (biology); Dextrose; Differentiation; DNA binding proteins; Energy balance; Enzymes; Fatty acids; Gene regulation; Genes; Glucose; Glucose metabolism; GTPase; Homeostasis; Insulin; Kinases; Lipids; Lipogenesis; lipogenic enzymes; Mice; Monomeric GTP-Binding Proteins - metabolism; Musculoskeletal system; Progenitor cells; Protein binding; Proteins; Rac1 protein; Scientific equipment and supplies industry; Stem Cells - metabolism; Transcription activation; Transcription factors; Triglycerides; Triglycerides - metabolism
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24054608

White adipocytes act as lipid storage, and play an important role in energy homeostasis. The small GTPase Rac1 has been implicated in the regulation of insulin-stimulated glucose uptake in white adipocytes. Adipocyte-specific -knockout (adipo- -KO) mice exhibit atrophy of subcutaneous and epididymal white adipose tissue (WAT); white adipocytes in these mice are significantly smaller than controls. Here, we aimed to investigate the mechanisms underlying the aberrations in the development of Rac1-deficient white adipocytes by employing in vitro differentiation systems. Cell fractions containing adipose progenitor cells were obtained from WAT and subjected to treatments that induced differentiation into adipocytes. In concordance with observations in vivo, the generation of lipid droplets was significantly attenuated in Rac1-deficient adipocytes. Notably, the induction of various enzymes responsible for de novo synthesis of fatty acids and triacylglycerol in the late stage of adipogenic differentiation was almost completely suppressed in Rac1-deficient adipocytes. Furthermore, the expression and activation of transcription factors, such as the CCAAT/enhancer-binding protein (C/EBP) β, which is required for the induction of lipogenic enzymes, were largely inhibited in Rac1-deficient cells in both early and late stages of differentiation. Altogether, Rac1 is responsible for adipogenic differentiation, including lipogenesis, through the regulation of differentiation-related transcription.