Glucose transporter 10 modulates adipogenesis via an ascorbic acid-mediated pathway to protect mice against diet-induced metabolic dysregulation
Autoři:
Chung-Lin Jiang aff001; Wei-Ping Jen aff001; Chang-Yu Tsao aff001; Li-Ching Chang aff002; Chien-Hsiun Chen aff002; Yi-Ching Lee aff001
Působiště autorů:
Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan
aff001; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
aff002
Vyšlo v časopise:
Glucose transporter 10 modulates adipogenesis via an ascorbic acid-mediated pathway to protect mice against diet-induced metabolic dysregulation. PLoS Genet 16(5): e32767. doi:10.1371/journal.pgen.1008823
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pgen.1008823
Souhrn
The development of type 2 diabetes mellitus (T2DM) depends on interactions between genetic and environmental factors, and a better understanding of gene-diet interactions in T2DM will be useful for disease prediction and prevention. Ascorbic acid has been proposed to reduce the risk of T2DM. However, the links between ascorbic acid and metabolic consequences are not fully understood. Here, we report that glucose transporter 10 (GLUT10) maintains intracellular levels of ascorbic acid to promote adipogenesis, white adipose tissue (WAT) development and protect mice from high-fat diet (HFD)-induced metabolic dysregulation. We found genetic polymorphisms in SLC2A10 locus are suggestively associated with a T2DM intermediate phenotype in non-diabetic Han Taiwanese. Additionally, mice carrying an orthologous human Glut10G128E variant (Glut10G128E mice) with compromised GLUT10 function have reduced adipogenesis, reduced WAT development and increased susceptibility to HFD-induced metabolic dysregulation. We further demonstrate that GLUT10 is highly expressed in preadipocytes, where it regulates intracellular ascorbic acid levels and adipogenesis. In this context, GLUT10 increases ascorbic acid-dependent DNA demethylation and the expression of key adipogenic genes, Cebpa and Pparg. Together, our data show GLUT10 regulates adipogenesis via ascorbic acid-dependent DNA demethylation to benefit proper WAT development and protect mice against HFD-induced metabolic dysregulation. Our findings suggest that SLC2A10 may be an important HFD-associated susceptibility locus for T2DM.
Klíčová slova:
Adipocytes – Adipokines – Adiponectin – Cell differentiation – Gene expression – Inflammation – Type 2 diabetes – vitamin C
Zdroje
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