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Induction of Adipocyte Differentiation by a Thiazolidinedione in Cultured, Subepidermal, Fibroblast-Like Cells of an Infant with Congenital Generalized Lipodystrophy

Department of Pediatrics, University of Ulm (P.F., K.M.D., M.W.), D-89075 Ulm, Germany; Department of Pathology, University of Ulm (P.M., I.M.), D-89070 Ulm, Germany; Department of Pediatrics, University of Bonn (L.B.), D-53113 Bonn, Germany; and Department of Diabetes Biology, Novo Nordisk A/S (H.T.), DK-2880 Bagsvaerd, Denmark

Address all correspondence and requests for reprints to: Martin Wabitsch, M.D., Department of Pediatrics, University of Ulm, Prittwitzstrasse 43, 89075 Ulm, Germany. E-mail: . martin.wabitsch{at}medizin.uni-ulm.de

Abstract

Congenital generalized lipodystrophy (CGL) is characterized by the absence of adipose tissue from birth due to a hypothetical differentiation block. The genetic causes of CGL are still not completely understood.

Subepidermal, fibroblast-like cells were prepared from the sc tissue of an infant with CGL. Preadipocytes from sc adipose tissue and foreskin fibroblasts from three healthy patients, respectively, were used as controls. Adipose differentiation was induced in cultured cells by exposure to 10 nM insulin, 200 pM T₃, 1 µM cortisol, and 2 µM rosiglitazone. Under these conditions 42% of the subepidermal, fibroblast-like CGL cells developed into mature adipocytes. Adipogenic differentiation was dependent on rosiglitazone. The differentiation rate was comparable in cultures of preadipocytes from control patients maintained under the same conditions (53%, 38%, and 20%). In contrast, foreskin fibroblasts did not differentiate into adipocytes. Morphological changes in CGL cells during differentiation were associated with the expression of fat cell-specific mRNAs (PPAR, leptin, and glut-4). In addition, these cells revealed characteristic features of mature adipocytes, such as lipogenesis or leptin secretion.

Taken together, we show that adipocyte precursor cells were present in subepidermal tissue of a patient with CGL and were able to differentiate into adipocytes in the presence of a thiazolidinedione. These findings strongly support clinical trials with thiazolidinediones in patients with CGL.

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