title: Loss of coiled-coil domain containing 80 negatively modulates glucose homeostasis in diet-induced obese mice.
abstract: Coiled-coil domain containing 80 (Ccdc80) is a secreted protein highly enriched in mouse and human white adipose tissue (WAT) that plays an important role during adipocyte differentiation in vitro. To investigate the physiological function of Ccdc80 in energy and glucose homeostasis, we generated mice in which the gene encoding Ccdc80 was disrupted. Mice lacking Ccdc80 showed increased sensitivity to diet-induced hyperglycemia and glucose intolerance while displaying reduced glucose-stimulated insulin secretion in vivo. Gene expression analysis by microarray revealed that only 10 transcripts were simultaneously altered in pancreas, skeletal muscle, and WAT from Ccdc80(-/-) mice, including some components of the circadian clock. Expression of the core clock member Arntl/Bmal1 was reduced whereas that of the oscillating transcription factors Dbp and Tef was increased in all tissues examined. Furthermore, knockdown of Ccdc80 in 3T3-L1 cells led to an increase of Dbp mRNA levels during adipocyte differentiation, suggesting that Ccdc80 might be involved in the regulation of this gene in a cell-autonomous manner. Importantly, transcriptional alterations in Ccdc80(-/-) mice were associated with changes in feeding behavior, increased caloric intake, decreased energy expenditure, and obesity. Taken together, our results suggest that Ccdc80 is a novel modulator of glucose and energy homeostasis during diet-induced obesity.
authors: Centers for Therapeutic Innovation, Pfizer Inc., 3 Blackfan Circle, Boston, Massachusetts 02115, USA. frederic.tremblay@pfizer.com
authors: Frédéric
authors: F
authors: Tremblay
authors: Christine
authors: C
authors: Huard
authors: Jessie
authors: J
authors: Dow
authors: Tiffany
authors: T
authors: Gareski
authors: Sarah
authors: S
authors: Will
authors: Ann-Marie
authors: AM
authors: Richard
authors: Jameel
authors: J
authors: Syed
authors: Steven
authors: S
authors: Bailey
authors: Karrie A
authors: KA
authors: Brenneman
authors: Robert V
authors: RV
authors: Martinez
authors: Mylène
authors: M
authors: Perreault
authors: Qingcong
authors: Q
authors: Lin
authors: Ruth E
authors: RE
authors: Gimeno
mesh_terms: D041721:3T3-L1 Cells; D056930:ARNTL Transcription Factors / Q000235:genetics / Q000378:metabolism; D052436:Adipose Tissue, White / Q000378:metabolism; D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D016326:Extracellular Matrix Proteins; D005947:Glucose / Q000378:metabolism*; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008820:Mice, Obese; D018482:Muscle, Skeletal / Q000378:metabolism; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D010179:Pancreas / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D056930:ARNTL Transcription Factors; C538961:Bmal1 protein, mouse; D050976:Basic-Leucine Zipper Transcription Factors; C448780:Ccdc80 protein, mouse; D004268:DNA-Binding Proteins; C498260:Dbp protein, mouse; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; C489491:Tef protein, mouse; D014157:Transcription Factors; D005947:Glucose