Breast cancer 1 (BrCa1) may be behind decreased lipogenesis in adipose tissue from obese subjects.
BACKGROUND
Expression and activity of the main lipogenic enzymes is paradoxically decreased in obesity, but the mechanisms behind these findings are poorly known. Breast Cancer 1 (BrCa1) interacts with acetyl-CoA carboxylase (ACC) reducing the rate of fatty acid biosynthesis. In this study, we aimed to evaluate BrCa1 in human adipose tissue according to obesity and insulin resistance, and in vitro cultured adipocytes.


METHODS
BrCa1 gene expression, total and phosphorylated (P-) BrCa1, and ACC were analyzed in adipose tissue samples obtained from a total sample of 133 subjects. BrCa1 expression was also evaluated during in vitro differentiation of human adipocytes and 3T3-L1 cells.


RESULTS
BrCa1 gene expression was significantly up-regulated in both omental (OM; 1.36-fold, p = 0.002) and subcutaneous (SC; 1.49-fold, p = 0.001) adipose tissue from obese subjects. In parallel with increased BrCa1 mRNA, P-ACC was also up-regulated in SC (p = 0.007) as well as in OM (p = 0.010) fat from obese subjects. Consistent with its role limiting fatty acid biosynthesis, both BrCa1 mRNA (3.5-fold, p<0.0001) and protein (1.2-fold, p = 0.001) were increased in pre-adipocytes, and decreased during in vitro adipogenesis, while P-ACC decreased during differentiation of human adipocytes (p = 0.005) allowing lipid biosynthesis. Interestingly, BrCa1 gene expression in mature adipocytes was restored by inflammatory stimuli (macrophage conditioned medium), whereas lipogenic genes significantly decreased.


CONCLUSIONS
The specular findings of BrCa1 and lipogenic enzymes in adipose tissue and adipocytes reported here suggest that BrCa1 might help to control fatty acid biosynthesis in adipocytes and adipose tissue from obese subjects.
Service of Diabetes, Endocrinology and Nutrition, Institut d'Investigació Biomèdica de Girona, CIBER de la Fisiopatología de la Obesidad y Nutrición, and Instituto de Salud Carlos III, Girona, Spain.
Francisco J
FJ
Ortega
José M
JM
Moreno-Navarrete
Dolores
D
Mayas
Eva
E
García-Santos
María
M
Gómez-Serrano
José I
JI
Rodriguez-Hermosa
Bartomeu
B
Ruiz
Wifredo
W
Ricart
Francisco J
FJ
Tinahones
Gema
G
Frühbeck
Belen
B
Peral
José M
JM
Fernández-Real
D041721:3T3-L1 Cells; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D000818:Animals; D019313:BRCA1 Protein / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D006801:Humans; D050155:Lipogenesis; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D009765:Obesity / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D019313:BRCA1 Protein; D012333:RNA, Messenger; D000103:Acetyl-CoA Carboxylase