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- Title
Regulation of Fat Accumulation by Tbx15.
- Authors
Gesta, Stephane; Bezy, Olivier; Kahn, C. Ronald
- Abstract
Accumulation of intra-abdominal adipose tissue is associated with a higher risk for development of type 2 diabetes and metabolic syndrome. In addition, intra-abdominal adipocytes differ from subcutaneous adipocytes in a variety of biochemical and cell biological properties including lipogenic and lipolytic activities. In a previous study, we reported that body fat accumulation and distribution appeared to be regulated by a number of developmental and patterning genes. One of the strongest correlations was a decrease in expression of the mesodermal developmental transcription factor Tbx15 in intra-abdominal and increase expression in subcutaneous adipose tissue. To understand the possible role of Tbx15 in adipocyte biology, we stably overexpressed Tbx 15 in 3T3-L1 preadipocytes and the plutipotent mesnchymal cell line C3H10T1/2, using retroviral transduction. In 3T3-L1 cells, when adipocyte differentiation was induced in absence of the PPARTγ agonist rosiglitazone, cells overexpressing Tbx15 showed a marked decrease in triglycerides accumulation and reduced expression of adipocytes marker CEBPα, PPARγ and aP2. Addition of rosiglitazone reversed this blockade allowing normal adipocyte differentiation and gene expression in Tbx15-overexpressing cells. Despite this normal level, of differentiation, Tbx15 overexpressing cells demonstrated a decrease in triglycerides accumulation. This was due to a decrease in basal lipogenic activity and an increase in basal lipolytic activity, similar to that seen normally in adipose of intra-abdominal depots. Maximal lipogenic and lipolytic responses to insulin and the βadrenergic agonist isoproterenol, on the other hand, were normal. In C3H10T1/2, Tbx 15 overexpression also lead to a marked decrease in triglycerides accumulation despite a normal expression of adipocyte markers. In summary, our data suggest that the developmental transcription factor Tbx15 can modulate the ability of preadipocytes to differentiate and accumulate triglycerides. These results suggest that a decrease of Tbx15 expression in intra-abdominal adipose tissue depots of obese patient with visceral adiposity could contribute to development and enlargement of adipocytes within this depot. This opens a new avenue of understanding fat accumulation and distribution, and its incidence on distinct risks associated to obesity, like diabetes. These findings also present new therapeutic target to modify obesity and the development of metabolic syndrome.
- Subjects
ADIPOSE tissues; TRANSCRIPTION factors; TYPE 2 diabetes; METABOLIC syndrome; GENE expression
- Publication
Diabetes, 2007, Vol 56, pA6
- ISSN
0012-1797
- Publication type
Article