The primary cilium undergoes dynamic size modifications during adipocyte differentiation of human adipose stem cells

Forcioli-Conti, Nicolas; Lacas‐Gervais, Sandra; Dani, Christian; Peraldi, Pascal

doi:10.1016/j.bbrc.2015.01.078

Cited by 48 publications

(64 citation statements)

References 31 publications

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“…Vismodegib has also been reported to suppress Gli1, a transcription factor of Ihh (54). Similarly, increase in primary cilium length is also known to inhibit Hh signaling (55) and Dexa increases cilium length (56). This may explain the possible connection between the use of GCs and decreased Hh signaling.…”

Section: Discussionmentioning

confidence: 99%

Humanin is a novel regulator of Hedgehog signaling and prevents glucocorticoid‐induced bone growth impairment

et al. 2019

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Glucocorticoids (GCs) are frequently used to treat chronic disorders in children, including inflammation and cancer. Prolonged treatment with GCs is well known to impair bone growth, an effect linked to increased apoptosis and suppressed proliferation in growth plate chondrocytes. We hypothesized that the endogenous antiapoptotic protein humanin (HN) may prevent these effects. Interestingly, GC‐induced bone growth impairment and chondrocyte apoptosis was prevented in HN overexpressing mice, HN‐treated wild‐type mice, and in HN‐treated cultured rat metatarsal bones. GC‐induced suppression of chondrocyte proliferation was also prevented by HN. Furthermore, GC treatment reduced Indian Hedgehog expression in growth plates of wild‐type mice but not in HN overexpressing mice or HN‐treated wild‐type animals. A Hedgehog (Hh) antagonist, vismodegib, was found to suppress the growth of cultured rat metatarsal bones, and this effect was also prevented by HN. Importantly, HN did not interfere with the desired anti‐inflammatory effects of GCs. We conclude that HN is a novel regulator of Hh signaling preventing GC‐induced bone growth impairment without interfering with desired effects of GCs. Our data may open for clinical studies exploring a new possible strategy to prevent GC‐induced bone growth impairment by cotreating with HN.—Zaman, F., Zhao, Y., Celvin, B., Mehta, H. H., Wan, J., Chrysis, D., Ohlsson, C, Fadeel, B., Cohen, P., Sävendahl, L. Humanin is a novel regulator of Hedgehog signaling and prevents glucocorticoid‐induced bone growth impairment. FASEB J. 33, 4962–4974 (2019). http://www.fasebj.org

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Section: Discussionmentioning

confidence: 99%

Humanin is a novel regulator of Hedgehog signaling and prevents glucocorticoid‐induced bone growth impairment

et al. 2019

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“…Studies by Forcioli-Conti and colleagues corroborate this work and show the importance of HDAC6. The importance of HDAC6 in regulating the cilium in this process is shown, but mechanisms involving other HDAC6 targets and interacting proteins cannot be ruled out 26, 27 . Our data support the possible involvement of improved adipocyte differentiation in the absence of HDAC6 as a means for increased fat deposition and weight gain in CF/HDA mice.…”

Section: Discussionmentioning

confidence: 99%

Improved Growth Patterns in Cystic Fibrosis Mice after Loss of Histone Deacetylase 6

Rymut

Corey

Valerio

et al. 2017

Sci Rep

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Growth failure in cystic fibrosis (CF) patients has been well-documented and shown to correlate with poorer disease outcomes. This observation is also true in CF animal models, including mouse, pig, rat, and ferret. The etiology underlying growth deficits is unknown, and our previous work demonstrated reduced tubulin acetylation in CF cell models and tissue that is correctable by inhibition of histone deacetylase-6 (HDAC6). Here, we hypothesize that loss of HDAC6 will improve growth phenotype in a CF mouse model. Hdac6 knockout mice were crossed with F508del (CF) mice to generate F508del/Hdac6 (CF/HDA) mice. Growth, fat deposits, survival, and bioelectric measurements were analyzed. CF/HDA mice displayed improvements in length and weight with no correction of CFTR function. Mechanistically, Igf1 levels likely account for increased length and improvements in fertility. Weight gain is attributed to increased fat deposits potentially mediated by increased adipocyte differentiation. CF-related growth deficits can be improved via inhibition of HDAC6, further implicating it as a potential therapeutic target for CF.

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“…During adipocyte differentiation of human adipose stem cells, the primary cilium goes through dynamic size modifications. This suggests that the cilium has various functions during adipogenesis [85]. A recent study by Seo S. et al [86] has shown that proteins distorted in the human ciliary disorder Bardet-Biedl syndrome (BBS proteins) are required for leptin receptor (LepR) signaling in the hypothalamus: (1) Bbs2(−/−), Bbs4(−/−) and Bbs6(−/−) mice are resistant to the action of leptin to reduce food intake and body weight; (2) BBS1 protein physically interacts with the leptin receptor (LepR).…”

Section: Discussionmentioning

confidence: 99%

A compendium of human genes regulating feeding behavior and body weight, its functional characterization and identification of GWAS genes involved in brain-specific PPI network

et al. 2016

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BackgroundObesity is heritable. It predisposes to many diseases. The objectives of this study were to create a compendium of genes relevant to feeding behavior (FB) and/or body weight (BW) regulation; to construct and to analyze networks formed by associations between genes/proteins; and to identify the most significant genes, biological processes/pathways, and tissues/organs involved in BW regulation.ResultsThe compendium of genes controlling FB or BW includes 578 human genes. Candidate genes were identified from various sources, including previously published original research and review articles, GWAS meta-analyses, and OMIM (Online Mendelian Inheritance in Man). All genes were ranked according to knowledge about their biological role in body weight regulation and classified according to expression patterns or functional characteristics. Substantial and overrepresented numbers of genes from the compendium encoded cell surface receptors, signaling molecules (hormones, neuropeptides, cytokines), transcription factors, signal transduction proteins, cilium and BBSome components, and lipid binding proteins or were present in the brain-specific list of tissue-enriched genes identified with TSEA tool. We identified 27 pathways from KEGG, REACTOME and BIOCARTA whose genes were overrepresented in the compendium. Networks formed by physical interactions or homological relationships between proteins or interactions between proteins involved in biochemical/signaling pathways were reconstructed and analyzed. Subnetworks and clusters identified by the MCODE tool included genes/proteins associated with cilium morphogenesis, signal transduction proteins (particularly, G protein–coupled receptors, kinases or proteins involved in response to insulin stimulus) and transcription regulation (particularly nuclear receptors). We ranked GWAS genes according to the number of neighbors in three networks and revealed 22 GWAS genes involved in the brain-specific PPI network. On the base of the most reliable PPIs functioning in the brain tissue, new regulatory schemes interpreting relevance to BW regulation are proposed for three GWAS genes (ETV5, LRP1B, and NDUFS3). ConclusionsA compendium comprising 578 human genes controlling FB or BW was designed, and the most significant functional groups of genes, biological processes/pathways, and tissues/organs involved in BW regulation were revealed. We ranked genes from the GWAS meta-analysis set according to the number and quality of associations in the networks and then according to their involvement in the brain-specific PPI network and proposed new regulatory schemes involving three GWAS genes (ETV5, LRP1B, and NDUFS3) in BW regulation. The compendium is expected to be useful for pathology risk estimation and for design of new pharmacological approaches in the treatment of human obesity.Electronic supplementary materialThe online version of this article (doi:10.1186/s12863-016-0466-2) contains supplementary material, which is available to authorized users.

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The primary cilium undergoes dynamic size modifications during adipocyte differentiation of human adipose stem cells

Cited by 48 publications

References 31 publications

Humanin is a novel regulator of Hedgehog signaling and prevents glucocorticoid‐induced bone growth impairment

Humanin is a novel regulator of Hedgehog signaling and prevents glucocorticoid‐induced bone growth impairment

Improved Growth Patterns in Cystic Fibrosis Mice after Loss of Histone Deacetylase 6

A compendium of human genes regulating feeding behavior and body weight, its functional characterization and identification of GWAS genes involved in brain-specific PPI network

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