Mesodermal developmental gene Tbx15 impairs adipocyte differentiation and mitochondrial respiration

Increased intraabdominal (visceral) fat is associated with a high risk of diabetes and metabolic syndrome. We have previously shown that the mesodermal developmental transcription factor Tbx15 is highly differentially expressed between visceral and subcutaneous (s.c.) fat in both humans and rodents,...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2011-02, Vol.108 (7), p.2771-2776
Main Authors: Gesta, Stephane, Bezy, Olivier, Mori, Marcelo A, Macotela, Yazmin, Lee, Kevin Y, Kahn, C. Ronald
Format: Article
Language:English
Subjects:
3T3-L1 Cells
Adenosine triphosphatase
Adenosine Triphosphate - metabolism
Adipocytes
Adipocytes - physiology
Adipose tissues
Animals
ATP
Azo Compounds
Biological Sciences
Cell Differentiation - drug effects
Cell Differentiation - genetics
Cell Differentiation - physiology
Cell Respiration - genetics
Cell Respiration - physiology
Cells
Cloning, Molecular
Developmental genes
Diabetes
Diabetes mellitus
Differentiation
DNA Primers - genetics
Electron transport
Energy Metabolism - physiology
Fatty acids
Gene expression
Genes
Male
Messenger RNA
Metabolic disorders
Metabolic syndrome
Mice
Mice, Inbred C57BL
Mitochondria
Mitochondria - physiology
Obesity
Oxygen Consumption - physiology
Peroxisome proliferator-activated receptors
Polymerase Chain Reaction
PPAR gamma - agonists
Preadipocytes
Respiration
Risk factors
Rodents
rosiglitazone
Subcutaneous Fat - metabolism
T-Box Domain Proteins - genetics
T-Box Domain Proteins - metabolism
Thiazolidinediones - pharmacology
Transcription factors
Triglycerides
Visceral fat
White adipose tissue
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Summary:Increased intraabdominal (visceral) fat is associated with a high risk of diabetes and metabolic syndrome. We have previously shown that the mesodermal developmental transcription factor Tbx15 is highly differentially expressed between visceral and subcutaneous (s.c.) fat in both humans and rodents, and in humans visceral fat Tbx15 expression is decreased in obesity. Here we show that, in mice, Tbx15 is 260-fold more highly expressed in s.c. preadipocytes than in epididymal preadipocytes. Overexpression of Tbx15 in 3T3-L1 preadipocytes impairs adipocyte differentiation and decreases triglyceride content. This defect in differentiation can be corrected by stimulating cells with the PPARĪ³ agonist rosiglitazone (Rosi). However, triglyceride accumulation remains decreased by ~50%, due to a decrease in basal lipogenic rate and increase in basal lipolytic rate. 3T3-L1 preadipocytes overexpressing Tbx15 also have a 15% reduction in mitochondrial mass and a 28% reduction in basal mitochondrial respiration (P = 0.004) and ATP turnover (P = 0.02), and a 45% (P = 0.003) reduction in mitochondrial respiratory capacity. Thus, differential expression of Tbx15 between fat depots plays an important role in the interdepot differences in adipocyte differentiation, triglyceride accumulation, and mitochondrial function that may contribute to the risk of diabetes and metabolic disease.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1019704108