title: Decreased RB1 mRNA, protein, and activity reflect obesity-induced altered adipogenic capacity in human adipose tissue.
abstract: Retinoblastoma (Rb1) has been described as an essential player in white adipocyte differentiation in mice. No studies have been reported thus far in human adipose tissue or human adipocytes. We aimed to investigate the possible role and regulation of RB1 in adipose tissue in obesity using human samples and animal and cell models. Adipose RB1 (mRNA, protein, and activity) was negatively associated with BMI and insulin resistance (HOMA-IR) while positively associated with the expression of adipogenic genes (PPARγ and IRS1) in both visceral and subcutaneous human adipose tissue. BMI increase was the main contributor to adipose RB1 downregulation. In rats, adipose Rb1 gene expression and activity decreased in parallel to dietary-induced weight gain and returned to baseline with weight loss. RB1 gene and protein expression and activity increased significantly during human adipocyte differentiation. In fully differentiated adipocytes, transient knockdown of Rb1 led to loss of the adipogenic phenotype. In conclusion, Rb1 seems to play a permissive role for human adipose tissue function, being downregulated in obesity and increased during differentiation of human adipocytes. Rb1 knockdown findings further implicate Rb1 as necessary for maintenance of adipogenic characteristics in fully differentiated adipocytes.
authors: Service of Diabetes, Endocrinology and Nutrition, Institut d'Investigació Biomèdica de Girona and CIBER Fisiopatología de la Obesidad y Nutrición CB06/03/010, Girona, Spain.
authors: José María
authors: JM
authors: Moreno-Navarrete
authors: Petar
authors: P
authors: Petrov
authors: Marta
authors: M
authors: Serrano
authors: Francisco
authors: F
authors: Ortega
authors: Estefanía
authors: E
authors: García-Ruiz
authors: Paula
authors: P
authors: Oliver
authors: Joan
authors: J
authors: Ribot
authors: Wifredo
authors: W
authors: Ricart
authors: Andreu
authors: A
authors: Palou
authors: M Luisa
authors: ML
authors: Bonet
authors: José Manuel
authors: JM
authors: Fernández-Real
mesh_terms: D050156:Adipogenesis / Q000235:genetics / Q000502:physiology; D000273:Adipose Tissue / Q000378:metabolism*; D050154:Adiposity / Q000235:genetics / Q000502:physiology; D000328:Adult; D005260:Female; D006801:Humans; D015151:Immunoblotting; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics*; D012175:Retinoblastoma / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger