Deleted in Breast Cancer 1 limits adipose tissue fat accumulation and plays a key role in the development of metabolic syndrome phenotype.
- Carlos Escande1,2,3,
- Veronica Nin1,2,
- Tamar Pirtskhalava1,
- Claudia C.S. Chini1,2,
- Tamar Tchkonia1,
- James L. Kirkland1 and
- Eduardo N. Chini1,2,*
- 1Kogod Aging Center, Mayo Clinic, Rochester, MN, USA
- 2Department of Anesthesiology, Mayo Clinic, Rochester, MN, USA
- 3Institut Pasteur Montevideo, Montevideo, Uruguay.
- *Corresponding Author: Eduardo Nunes Chini, E-mail:
Obesity is often regarded as the primary cause of metabolic syndrome. However, many lines of evidence suggest that obesity may develop as a protective mechanism against tissue damage during caloric surplus, and it is only when the maximum fat accumulation capacity is reached and fatty acid spillover occurs into to peripheral tissues, that metabolic diseases develop. In this regard it is imperative to identify the molecular mechanisms that modulate adipocyte fat accumulation and fatty acid spillover. Here we identify the protein Deleted in Breast Cancer 1 (DBC1) as a key regulator of fat storage capacity of adipocytes. We found that knockout of DBC1 facilitates fat cell differentiation, lipid accumulation, and increases fat storage capacity of adipocytes in vitro and in vivo. This effect resulted in a “healthy obesity” phenotype. DBC1 KO mice in a high fat diet, although obese, remained insulin sensitive, had lower FFA in plasma, were protected against atherosclerosis, liver steatosis and lived longer. We propose that DBC1 is part of the molecular machinery that regulates fat storage capacity in adipocytes and participates in the “turn-off” switch that limits adipocyte fat accumulation and leads to fat spillover into peripheral tissues, leading to the deleterious effects of caloric surplus.
- Received February 3, 2014.
- Accepted July 15, 2014.
- © 2014 by the American Diabetes Association.
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