Regulation of adipose differentiation by fructose and GluT5

Mol Endocrinol. 2012 Oct;26(10):1773-82. doi: 10.1210/me.2012-1122. Epub 2012 Jul 24.

Abstract

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 although the mechanism(s) remain unclear. Differentiation of preadipocytes to mature adipocytes is a highly regulated process that is associated with characteristic sequential changes in adipocyte gene expression. We demonstrate that fructose treatment of murine 3T3-L1 cells incubated in standard differentiation 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / metabolism
  • Adipocytes / physiology
  • Adipogenesis*
  • Adipose Tissue, White / cytology
  • Adipose Tissue, White / physiology
  • Adiposity
  • Animals
  • Fructose / pharmacology
  • Fructose / physiology*
  • Gene Expression
  • Gene Knockdown Techniques
  • Glucose Transport Proteins, Facilitative / genetics
  • Glucose Transport Proteins, Facilitative / metabolism
  • Glucose Transport Proteins, Facilitative / physiology*
  • Glucose Transporter Type 5
  • Mice
  • Mice, Knockout
  • RNA Interference

Substances

  • Glucose Transport Proteins, Facilitative
  • Glucose Transporter Type 5
  • Slc2a5 protein, mouse
  • Fructose