Adipose tissue is an important metabolic organ that is crucial for whole-body insulin sensitivity and energy homeostasis. Highly refined fructose intake increases visceral adiposity al- though the mechanism(s) remain unclear. Differentiation of preadipocytes to mature adipocytes is a highly regulated process that is associated with characteristic sequential changes in adi- pocyte gene expression. We demonstrate that fructose treat- ment of murine 3T3-L1 cells incubated in standard differentia- tion medium increases adipogenesis and adipocyte-related gene expression. We further show that the key fructose transporter, GluT5, is expressed in early-stage adipocyte differentiation but is not expressed in mature adipocytes. GluT5 overexpression or knockdown increased and decreased adipocyte differentiation, respectively, and treatment of 3T3-L1 cells with a specific GluT5 inhibitor decreased adipocyte differentiation. Epidymal white adipose tissue was reduced in GluT5—/— mice compared with wild-type mice, and mouse embryonic fibroblasts derived from GluT5—/— mice exhibited impaired adipocyte differentiation. Taken together, these results demonstrate that fructose and GluT5 play an important role in regulating adipose differentiation.
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