Reduced adipogenic gene expression in fibroblasts from a patient with type 2 congenital generalized lipodystrophy

B. Victoria, J. M. Cabezas-Agrícola, B. González-Méndez, G. Lattanzi, R. Del Coco, L. Loidi, F. Barreiro, C. Calvo, J. Lado-Abeal, D. Araújo-Vilar

Research output: Contribution to journalArticle

Abstract

Diabet. Med. 27, 1178-1187 (2010) AbstractAims Beradinelli-Seip congenital generalized lipodystrophy is a rare autosomal recessive disorder characterized by near-complete absence of adipose tissue, Herculean appearance, insulin resistance, hypoleptinaemia and diabetes mellitus. The aim of this study was to investigate the in vitro effects of pioglitazone on the expression of genes involved in adipogenesis in fibroblasts from a patient with this condition due to a seipin mutation. Methods Primary cultures of fibroblasts from the skin of the patient were obtained. Fibroblasts were treated with classic adipose differentiation medium, with and without pioglitazone. Several adipogenes were evaluated by real-time reverse transcriptase-polymerase chain reaction and western blotting. Intracellular localization of prelamin A was studied by immunofluorescence microscopy. Results The expression of the adipogenic genes PPARG, LPL, LEP and SLC2A4 was reduced in lipodystrophic fibroblasts, while treatment with pioglitazone increased the expression of these genes. Moreover, and unexpectedly, we found an accumulation of farnesylated prelamin A in lipodystrophic fibroblasts. Conclusions The process of adipocyte differentiation is compromised in patients with Beradinelli-Seip congenital lipodystrophy owing to diminished expression of the regulatory genes involved, which pioglitazone treatment partially rescues. Prelamin A accumulation establishes a link with other types of familial lipodystrophies, as familial partial lipodystrophy.

Original languageEnglish
Pages (from-to)1178-1187
Number of pages10
JournalDiabetic Medicine
Volume27
Issue number10
DOIs
Publication statusPublished - Oct 2010

Fingerprint

pioglitazone
Congenital Generalized Lipodystrophy
Fibroblasts
Gene Expression
Lipodystrophy
Familial Partial Lipodystrophy
Adipogenesis
Regulator Genes
Reverse Transcriptase Polymerase Chain Reaction
Fluorescence Microscopy
Adipocytes
Insulin Resistance
Adipose Tissue
Real-Time Polymerase Chain Reaction
Diabetes Mellitus
Western Blotting
Skin
Mutation
Therapeutics

Keywords

  • Beradinelli-Seip syndrome
  • fibroblast
  • gene expression
  • glitazone
  • seipin

ASJC Scopus subject areas

  • Endocrinology
  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Victoria, B., Cabezas-Agrícola, J. M., González-Méndez, B., Lattanzi, G., Del Coco, R., Loidi, L., ... Araújo-Vilar, D. (2010). Reduced adipogenic gene expression in fibroblasts from a patient with type 2 congenital generalized lipodystrophy. Diabetic Medicine, 27(10), 1178-1187. https://doi.org/10.1111/j.1464-5491.2010.03052.x

Reduced adipogenic gene expression in fibroblasts from a patient with type 2 congenital generalized lipodystrophy. / Victoria, B.; Cabezas-Agrícola, J. M.; González-Méndez, B.; Lattanzi, G.; Del Coco, R.; Loidi, L.; Barreiro, F.; Calvo, C.; Lado-Abeal, J.; Araújo-Vilar, D.

In: Diabetic Medicine, Vol. 27, No. 10, 10.2010, p. 1178-1187.

Research output: Contribution to journalArticle

Victoria, B, Cabezas-Agrícola, JM, González-Méndez, B, Lattanzi, G, Del Coco, R, Loidi, L, Barreiro, F, Calvo, C, Lado-Abeal, J & Araújo-Vilar, D 2010, 'Reduced adipogenic gene expression in fibroblasts from a patient with type 2 congenital generalized lipodystrophy', Diabetic Medicine, vol. 27, no. 10, pp. 1178-1187. https://doi.org/10.1111/j.1464-5491.2010.03052.x
Victoria, B. ; Cabezas-Agrícola, J. M. ; González-Méndez, B. ; Lattanzi, G. ; Del Coco, R. ; Loidi, L. ; Barreiro, F. ; Calvo, C. ; Lado-Abeal, J. ; Araújo-Vilar, D. / Reduced adipogenic gene expression in fibroblasts from a patient with type 2 congenital generalized lipodystrophy. In: Diabetic Medicine. 2010 ; Vol. 27, No. 10. pp. 1178-1187.
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abstract = "Diabet. Med. 27, 1178-1187 (2010) AbstractAims Beradinelli-Seip congenital generalized lipodystrophy is a rare autosomal recessive disorder characterized by near-complete absence of adipose tissue, Herculean appearance, insulin resistance, hypoleptinaemia and diabetes mellitus. The aim of this study was to investigate the in vitro effects of pioglitazone on the expression of genes involved in adipogenesis in fibroblasts from a patient with this condition due to a seipin mutation. Methods Primary cultures of fibroblasts from the skin of the patient were obtained. Fibroblasts were treated with classic adipose differentiation medium, with and without pioglitazone. Several adipogenes were evaluated by real-time reverse transcriptase-polymerase chain reaction and western blotting. Intracellular localization of prelamin A was studied by immunofluorescence microscopy. Results The expression of the adipogenic genes PPARG, LPL, LEP and SLC2A4 was reduced in lipodystrophic fibroblasts, while treatment with pioglitazone increased the expression of these genes. Moreover, and unexpectedly, we found an accumulation of farnesylated prelamin A in lipodystrophic fibroblasts. Conclusions The process of adipocyte differentiation is compromised in patients with Beradinelli-Seip congenital lipodystrophy owing to diminished expression of the regulatory genes involved, which pioglitazone treatment partially rescues. Prelamin A accumulation establishes a link with other types of familial lipodystrophies, as familial partial lipodystrophy.",
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AU - Cabezas-Agrícola, J. M.

AU - González-Méndez, B.

AU - Lattanzi, G.

AU - Del Coco, R.

AU - Loidi, L.

AU - Barreiro, F.

AU - Calvo, C.

AU - Lado-Abeal, J.

AU - Araújo-Vilar, D.

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N2 - Diabet. Med. 27, 1178-1187 (2010) AbstractAims Beradinelli-Seip congenital generalized lipodystrophy is a rare autosomal recessive disorder characterized by near-complete absence of adipose tissue, Herculean appearance, insulin resistance, hypoleptinaemia and diabetes mellitus. The aim of this study was to investigate the in vitro effects of pioglitazone on the expression of genes involved in adipogenesis in fibroblasts from a patient with this condition due to a seipin mutation. Methods Primary cultures of fibroblasts from the skin of the patient were obtained. Fibroblasts were treated with classic adipose differentiation medium, with and without pioglitazone. Several adipogenes were evaluated by real-time reverse transcriptase-polymerase chain reaction and western blotting. Intracellular localization of prelamin A was studied by immunofluorescence microscopy. Results The expression of the adipogenic genes PPARG, LPL, LEP and SLC2A4 was reduced in lipodystrophic fibroblasts, while treatment with pioglitazone increased the expression of these genes. Moreover, and unexpectedly, we found an accumulation of farnesylated prelamin A in lipodystrophic fibroblasts. Conclusions The process of adipocyte differentiation is compromised in patients with Beradinelli-Seip congenital lipodystrophy owing to diminished expression of the regulatory genes involved, which pioglitazone treatment partially rescues. Prelamin A accumulation establishes a link with other types of familial lipodystrophies, as familial partial lipodystrophy.

AB - Diabet. Med. 27, 1178-1187 (2010) AbstractAims Beradinelli-Seip congenital generalized lipodystrophy is a rare autosomal recessive disorder characterized by near-complete absence of adipose tissue, Herculean appearance, insulin resistance, hypoleptinaemia and diabetes mellitus. The aim of this study was to investigate the in vitro effects of pioglitazone on the expression of genes involved in adipogenesis in fibroblasts from a patient with this condition due to a seipin mutation. Methods Primary cultures of fibroblasts from the skin of the patient were obtained. Fibroblasts were treated with classic adipose differentiation medium, with and without pioglitazone. Several adipogenes were evaluated by real-time reverse transcriptase-polymerase chain reaction and western blotting. Intracellular localization of prelamin A was studied by immunofluorescence microscopy. Results The expression of the adipogenic genes PPARG, LPL, LEP and SLC2A4 was reduced in lipodystrophic fibroblasts, while treatment with pioglitazone increased the expression of these genes. Moreover, and unexpectedly, we found an accumulation of farnesylated prelamin A in lipodystrophic fibroblasts. Conclusions The process of adipocyte differentiation is compromised in patients with Beradinelli-Seip congenital lipodystrophy owing to diminished expression of the regulatory genes involved, which pioglitazone treatment partially rescues. Prelamin A accumulation establishes a link with other types of familial lipodystrophies, as familial partial lipodystrophy.

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