title: Deleted in breast cancer 1 limits adipose tissue fat accumulation and plays a key role in the development of metabolic syndrome phenotype.
abstract: 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 that 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, identifying the molecular mechanisms that modulate adipocyte fat accumulation and fatty acid spillover is imperative. Here we identify the deleted in breast cancer 1 (DBC1) protein as a key regulator of fat storage capacity of adipocytes. We found that knockout (KO) of DBC1 facilitated fat cell differentiation and lipid accumulation and increased fat storage capacity of adipocytes in vitro and in vivo. This effect resulted in a "healthy obesity" phenotype. DBC1 KO mice fed a high-fat diet, although obese, remained insulin sensitive, had lower free fatty acid in plasma, were protected against atherosclerosis and 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.
authors: Kogod Aging Center, Mayo Clinic, Rochester, MN Department of Anesthesiology, Mayo Clinic, Rochester, MN Institut Pasteur Montevideo, Montevideo, Uruguay.
authors: Carlos
authors: C
authors: Escande
authors: Kogod Aging Center, Mayo Clinic, Rochester, MN Department of Anesthesiology, Mayo Clinic, Rochester, MN.
authors: Veronica
authors: V
authors: Nin
authors: Kogod Aging Center, Mayo Clinic, Rochester, MN.
authors: Tamar
authors: T
authors: Pirtskhalava
authors: Kogod Aging Center, Mayo Clinic, Rochester, MN Department of Anesthesiology, Mayo Clinic, Rochester, MN.
authors: Claudia C S
authors: CC
authors: Chini
authors: Kogod Aging Center, Mayo Clinic, Rochester, MN.
authors: Tamar
authors: T
authors: Tchkonia
authors: Kogod Aging Center, Mayo Clinic, Rochester, MN.
authors: James L
authors: JL
authors: Kirkland
authors: Kogod Aging Center, Mayo Clinic, Rochester, MN Department of Anesthesiology, Mayo Clinic, Rochester, MN chini.eduardo@mayo.edu.
authors: Eduardo N
authors: EN
authors: Chini
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D001011:Aorta / Q000166:cytology; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005234:Fatty Liver / Q000235:genetics / Q000378:metabolism; D005260:Female; D005990:Glycerol / Q000378:metabolism; D006801:Humans; D024821:Metabolic Syndrome / Q000235:genetics / Q000378:metabolism*; D018345:Mice, Knockout; D009765:Obesity / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D056564:Sirtuin 1 / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology; D017154:Stromal Cells / Q000166:cytology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C527450:CCAR2 protein, human; D005230:Fatty Acids, Nonesterified; C000595916:KIAA1967 protein, mouse; C447939:SIRT1 protein, human; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; D005990:Glycerol