Soluble CRTC3: A Newly Identified Protein Released by Adipose Tissue That Is Associated with Childhood Obesity

Prats‐Puig, Anna; Soriano-Rodríguez, Pilar; Oliveras, Glòria; Carreras‐Badosa, Gemma; Espuña, Sílvia; Díaz-Roldán, Ferran; Zegher, Francis de; Ibáñez, Lourdes; Bassols, Judit; Puig, Teresa; López‐Bermejo, Abel

doi:10.1373/clinchem.2015.249136

Cited by 11 publications

(10 citation statements)

References 37 publications

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“…From the whole transcriptome analysis, we found 1 upregulated gene and 8 downregulated genes in Wilson's disease-HLCs, and these findings might provide invaluable information in future research for developing new therapeutics of Wilson's disease. For example, several studies showed that the CRTC3, a commonly upregulated gene in Wilson's disease HLCs of this study, is linked with obesity [43] and hepatic steatosis [44]. Because the fat accumulation is frequently observed in the liver of Wilson's disease patients, targeting CRTC3 possibly provides a new concurrent treatment with existing medications (e.g., copper chelators) for Wilson's disease patients.…”

Section: Discussionmentioning

confidence: 80%

Human Embryonic Stem Cell-Derived Wilson’s Disease Model for Screening Drug Efficacy

Kim¹,

Kim²,

Ryu³

et al. 2020

Cells

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Human pluripotent stem cells (hPSCs) including human embryonic stem cells (hESCs) and human-induced pluripotent stem cells (hiPSCs) have been extensively studied as an alternative cellular model for recapitulating phenotypic and pathophysiologic characters of human diseases. Particularly, hiPSCs generated from the genetic disease somatic cells could provide a good cellular model to screen potential drugs for treating human genetic disorders. However, the patient-derived cellular model has a limitation when the patient samples bearing genetic mutations are difficult to obtain due to their rarity. Thus, in this study, we explored the potential use of hPSC-derived Wilson’s disease model generated without a patient sample to provide an alternative approach for modeling human genetic disease by applying gene editing technology. Wilson’s disease hPSCs were generated by introducing a R778L mutation in the ATP7B gene (c.2333G>T) using Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 system into wildtype hESCs. Established Wilson’s disease hESCs were further differentiated into hepatocyte-like cells (HLCs) and analyzed for disease phenotypes and responses against therapeutic agent treatment. R778L mutation in the ATP7B gene was successfully introduced into wildtype hESCs, and the introduction of the mutation neither altered the self-renewal ability of hESCs nor the differentiation capability into HLCs. However, R778L mutation-introduced HLCs exhibited higher vulnerability against excessive copper supplementation than wildtype HLCs. Finally, the applicability of the R778L mutation introduced HLCs in drug screening was further demonstrated using therapeutic agents against the Wilson’s diseases. Therefore, the established model in this study could effectively mimic the Wilson’s disease without patient’s somatic cells and could provide a reliable alternative model for studying and drug screening of Wilson’s disease.

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Section: Discussionmentioning

confidence: 80%

Human Embryonic Stem Cell-Derived Wilson’s Disease Model for Screening Drug Efficacy

Kim¹,

Kim²,

Ryu³

et al. 2020

Cells

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“…Polymorphisms of CRTC1 and CRTC3 are associated with total cholesterol level in plasma, as well as high BMI, obesity and hypertriglyceridemia in Mexican-Americans, Chinese populations and psychiatric patients [14,36,37]. In addition, CRTC3 is found in circulation, partly as a result of adipose tissue secretion in childhood obesity [38], suggesting CRTC3 might have effects in other tissues beyond adipose and act as a “physiological messenger” during obesity. Most recently, polymorphisms in the CRTC1 loci show a significance genome-wide association with body fat percentage.…”

Section: Crtcs and Metabolic Disordersmentioning

confidence: 99%

Deregulation of CRTCs in Aging and Age-Related Disease Risk

2017

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Advances in public health in the last century have seen a sharp increase in human life expectancy. With these changes have come increased incidence of age-related pathologies and health burdens in the elderly. Patient age is the biggest risk factor for multiple chronic conditions that often occur simultaneously within one individual. An alternative to disease centric therapeutic approaches is that of ‘geroscience’, which aims to define molecular mechanisms that link age to overall disease risk. One such mechanism is deregulation of CREB-regulated transcriptional coactivators, CRTCs. Initially identified for their role in modulating CREB transcription, the last five years has seen an expansion in knowledge of new cellular regulators and roles of CRTCs beyond CREB. CRTCs have been shown to modulate organismal aging in C. elegans and to impact age-related diseases in humans. Here, we discuss CRTC deregulation as a new driver of aging, and integrating link between age and disease risk.

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“…Indeed, CRTC3 is associated with increased obesity risk in Mexican–Americans (Song et al, ). In addition, the serum concentration of CRTC3 has been identified as a new metabolic marker that is related to childhood obesity (Prats‐Puig et al, ). Thus, CRTC3 might be a promising target for the treatment of obesity and related disorders.…”

Section: Role Of Crtc3 In Adipocytementioning

confidence: 99%

Regulation role of CRTC3 in skeletal muscle and adipose tissue

Liu

et al. 2017

Journal Cellular Physiology

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The cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) signaling pathway plays important role in regulating energy homeostasis. Many of the effects of the cAMP-PKA signaling is mediated through the cAMP responsive element binding protein (CREB) and its coactivator CREB-regulated transcription coactivators (CRTCs). CRTC3 is a member of CRTCs family proteins and plays important roles in glucose and energy metabolism. Previous studies show that global knockout of CRTC3 enhances oxygen consumption and energy expenditure and subsequently protects the knockout animal against obesity. In skeletal muscle, CRTC3 affects lipid and glycogen metabolism and mitochondrial biogenesis. In white adipocytes, CRTC3 regulates GLUT4 expression and glucose uptake. More recently, the localization and function of CRTC3 in brown fat have been reported. In this review, we mainly discuss the regulatory role of CRTC3 in skeletal muscle and adipose tissues.

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Soluble CRTC3: A Newly Identified Protein Released by Adipose Tissue That Is Associated with Childhood Obesity

Cited by 11 publications

References 37 publications

Human Embryonic Stem Cell-Derived Wilson’s Disease Model for Screening Drug Efficacy

Human Embryonic Stem Cell-Derived Wilson’s Disease Model for Screening Drug Efficacy

Deregulation of CRTCs in Aging and Age-Related Disease Risk

Regulation role of CRTC3 in skeletal muscle and adipose tissue

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