Loss of DRO1/CCDC80 results in obesity and promotes adipocyte differentiation

Grill, Jessica I.; Neumann, Jens; Herbst, Andreas; Ofner, Andrea; Hiltwein, Felix; Marschall, Maximilian K.; Zierahn, Heike; Wolf, Eckhard; Schneider, Marlon R.; Kolligs, Frank T.

doi:10.1016/j.mce.2016.09.014

Cited by 20 publications

(18 citation statements)

References 24 publications

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“…Interestingly, Ccdc80-null mice on a high-fat diet show exacerbated glucose intolerance and hyperglycemia (9,29), leading to the proposal that CCDC80 might contribute to limiting some of the metabolic dysfunctions associated with diet-induced obesity. However, as the authors point out (29), some criticism can arise from this interpretation, considering that changes in glucose metabolism in ccdc80-null mice could develop secondary to the early increment in fat mass compared with controls, and likely due to loss of inhibition of adipogenesis. Glucose-stimulated insulin secretion in high-fat diets is impaired in Ccdc80-null mice, although the ability of isolated islets to secrete insulin is unaltered (9).…”

Section: Relationship Of Circulating Ccdc80 Protein To Obesity In Humansmentioning

confidence: 99%

“…Although the precise role of CCDC80 is not yet clear, results from mouse models suggest that CCDC80 might function to modulate glucose and energy homeostasis (9,29). The high expression of CCDC80 in WAT might point to a role as a local adipose factor inhibiting adipocyte differentiation (29); alternatively, CCDC80 might act as a circulating factor.…”

Section: Relationship Of Circulating Ccdc80 Protein To Obesity In Humansmentioning

confidence: 99%

“…The high expression of CCDC80 in WAT might point to a role as a local adipose factor inhibiting adipocyte differentiation (29); alternatively, CCDC80 might act as a circulating factor. Previous studies in mice have failed to detect CCDC80 protein in serum (9).…”

Section: Relationship Of Circulating Ccdc80 Protein To Obesity In Humansmentioning

confidence: 99%

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Adipose Tissue and Serum CCDC80 in Obesity and Its Association with Related Metabolic Disease

Osorio-Conles

Guitart

Moreno-Navarrete

et al. 2017

Mol Med

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Section: Relationship Of Circulating Ccdc80 Protein To Obesity In Humansmentioning

confidence: 99%

Section: Relationship Of Circulating Ccdc80 Protein To Obesity In Humansmentioning

confidence: 99%

See 1 more Smart Citation

Adipose Tissue and Serum CCDC80 in Obesity and Its Association with Related Metabolic Disease

Osorio-Conles

Guitart

Moreno-Navarrete

et al. 2017

Mol Med

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“…Glucose is a pivotal source of cellular energy from food digestion (Yang, 2014). In this study, we identified expression of the hub genes associated with multiple feed efficiency-related traits involved in glucose homeostasis, e.g., the CCDC80 gene, a potential negative regulator of adipogenesis whose dysfunction can lead to excessive body fat in mice (Grill et al, 2017). The hub gene OGN encodes a putative humoral anabolic bone factor protein produced in muscle tissue (Kaji, 2014) and previously identified as DE in liver samples from pigs divergent for RFI (Vigors et al, 2019).…”

Section: Energy Balancementioning

confidence: 99%

Potential Biomarkers for Feed Efficiency-Related Traits in Nelore Cattle Identified by Co-expression Network and Integrative Genomics Analyses

Lima

Diniz

et al. 2020

Front. Genet.

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Feed efficiency helps to reduce environmental impacts from livestock production, improving beef cattle profitability. We identified potential biomarkers (hub genes) for feed efficiency, by applying co-expression analysis in Longissimus thoracis RNA-Seq data from 180 Nelore steers. Six co-expression modules were associated with six feed efficiency-related traits (p-value ≤ 0.05). Within these modules, 391 hub genes were enriched for pathways as protein synthesis, muscle growth, and immune response. Trait-associated transcription factors (TFs) ELF1, ELK3, ETS1, FLI1, and TCF4, were identified with binding sites in at least one hub gene. Gene expression of CCDC80, FBLN5, SERPINF1, and OGN was associated with multiple feed efficiency-related traits (FDR ≤ 0.05) and were previously related to glucose homeostasis, oxidative stress, fat mass, and osteoblastogenesis, respectively. Potential regulatory elements were identified, integrating the hub genes with previous studies from our research group, such as the putative cis-regulatory elements (eQTLs) inferred as affecting the PCDH18 and SPARCL1 hub genes related to immune system and adipogenesis, respectively. Therefore, our analyses contribute to a better understanding of the biological mechanisms underlying feed efficiency in bovine and the hub genes disclosed can be used as biomarkers for feed efficiency-related traits in Nelore cattle.

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“…Collectively, these findings suggest that CCDC80 might participate in the underlying mechanism of combination treatment of vactosertib with nal-IRI/5-FU/LV in suppressing invasiveness and subsequent pancreatic cancer progression.Scientific RepoRtS | (2020) 10:2935 | https://doi.According to previous studies, CCDC80 (Dro1) is a secreted protein induced by oestrogen 43 . It plays a role in osteoblast and adipocyte differentiation, embryonic skeletal development, and glucose homeostasis 44,45 . In regard to cancer, mRNA expression of CCDC80 is often down-regulated in various cancer cell lines and tumour tissues, suggesting the tumour-suppressive role of CCDC80 24,43,46,47 .…”

mentioning

confidence: 99%

Inhibition of TGF-β signalling in combination with nal-IRI plus 5-Fluorouracil/Leucovorin suppresses invasion and prolongs survival in pancreatic tumour mouse models

Hong

Park

Ooshima

et al. 2020

Sci Rep

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Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies. TGF-β is strongly expressed in both the epithelial and stromal compartments of PDAC, and dysregulation of TGF-β signalling is a frequent molecular disturbance in PDAC progression and metastasis. In this study, we investigated whether blockade of TGF-β signalling synergizes with nal-IRI/5-FU/LV, a chemotherapy regimen for malignant pancreatic cancer, in an orthotopic pancreatic tumour mouse model. Compared to nal-IRI/5-FU/LV treatment, combining nal-IRI/5-FU/LV with vactosertib, a TGF-β signalling inhibitor, significantly improved long-term survival rates and effectively suppressed invasion to surrounding tissues. Through RNA-sequencing analysis, we identified that the combination treatment results in robust abrogation of tumour-promoting gene signatures and positive enrichment of tumoursuppressing and apoptotic gene signatures. Particularly, the expression of tumour-suppressing gene Ccdc80 was induced by vactosertib and further induced by vactosertib in combination with nal-IRI/5-FU/ LV. Ectopic expression of CCDC80 suppressed migration and colony formation concomitant with decreased expression of epithelial-to-mesenchymal transition (EMT) markers in pancreatic cancer cells. Collectively, these results indicate that combination treatment of vactosertib with nal-IRI/5-FU/LV improves overall survival rates in a mouse model of pancreatic cancer by suppressing invasion through CCDC80. Therefore, combination therapy of nal-IRI/5-FU/LV with vactosertib could provide clinical benefits to pancreatic cancer patients.Pancreatic cancer is one of the leading causes of cancer-related mortality in the world. The 5-year relative survival rate of pancreatic ductal adenocarcinoma (PDAC) patients was only 8% for all stages combined data in 2018 1 . Although 5-year relative survival rates in other cancer types have steadily increased over the years, improvement in pancreatic cancer is very slow because patients with pancreatic cancer are often diagnosed at advanced stages due to absence of noticeable symptoms in the early stages 2,3 . Moreover, control of pancreatic cancer is difficult owing to its aggressiveness, distal metastasis, resistance to most common treatments, and genetic and epigenetic alterations 4-6 .The pancreatic cancer treatment paradigm has improved in the last 20 years. In clinical trials in the 1970s, 5-fluorouracil (5-FU) was used after resection 7 . Nowadays, the combination treatments such as FOLFIRINOX (oxaliplatin, irinotecan, fluorouracil (5-FU), and leucovorin (LV)) and gemcitabine plus nab-paclitaxel are the novel chemotherapy regimens used for patients with metastatic pancreatic adenocarcinoma (mPAC), displaying significantly better patient outcomes compared to the commonly used gemcitabine and providing the chance for salvage chemotherapy [8][9][10] . Nanoliposomal irinotecan (nal-IRI) has different pharmacokinetic properties from irinotecan owing to the outer PEGylated liposomes encapsulating the irinotecan sucrosofate ...

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Loss of DRO1/CCDC80 results in obesity and promotes adipocyte differentiation

Cited by 20 publications

References 24 publications

Adipose Tissue and Serum CCDC80 in Obesity and Its Association with Related Metabolic Disease

Adipose Tissue and Serum CCDC80 in Obesity and Its Association with Related Metabolic Disease

Potential Biomarkers for Feed Efficiency-Related Traits in Nelore Cattle Identified by Co-expression Network and Integrative Genomics Analyses

Inhibition of TGF-β signalling in combination with nal-IRI plus 5-Fluorouracil/Leucovorin suppresses invasion and prolongs survival in pancreatic tumour mouse models

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