CGI-58: Versatile Regulator of Intracellular Lipid Droplet Homeostasis

Yu, Liqing; Li, Yang; Grisé, Alison; Wang, Huan

doi:10.1007/978-981-15-6082-8_13

Cited by 20 publications

(21 citation statements)

References 266 publications

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“…HSL is additionally phosphorylated (S600) and activated by ERK1/2 in response to mitogens, growth factors or cytokine signalling via the mitogen-activated protein kinase (MAPK) pathway 79 . Perilipin-1 phosphorylation is required for HSL translocation, but also triggers its dissociation from CGI-58, thereby enabling CGI-58 to interact with ATGL and to activate enzyme activity 112 (Fig. 3).…”

Section: Adiposementioning

confidence: 99%

Lipolysis: cellular mechanisms for lipid mobilization from fat stores

et al. 2021

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Section: Adiposementioning

confidence: 99%

Lipolysis: cellular mechanisms for lipid mobilization from fat stores

et al. 2021

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“…Recent studies have characterized another LDAP, ABHD5, also known as CGI-58. ABHD5 localized at cytosolic LDs [111]. PKA phosphorylates both ABHD5 and PLIN5, subsequently dissociating ABHD5 from PLIN5, resulting in the activation of ATGL [112, 113].…”

Section: Ldaps and Cardiomyopathymentioning

confidence: 99%

“…In humans, mutations in genes encoding ABHD5 can lead to a rare and fatal syndrome called the Chanarin-Dorfman syndrome (CDS), also neutral lipid storage disease (NLSD) [114, 115]. CDS is characterized by the accumulation of TAG-rich cytoplasmic LDs in most cell types including the cardiomyocytes, and the patients often manifest cardiomyopathy [111]. Although both ABHD5 and ATGL are associated with TAG accumulation in tissues, studies have revealed that their functions are not entirely bound together.…”

Section: Ldaps and Cardiomyopathymentioning

confidence: 99%

“…On the one hand, patients with impaired ATGL function develop more severe myopathy, whereas mutations in the genes encoding ABHD5 are more associated with the development of ichthyosis, which was unobservable in patients with ATGL deficiency [116]. On the other hand, ABHD5 is found to interact with numerous other lipolysis-regulatory proteins, including PLIN1, PLIN2, PLIN3, and PLIN5 in the PAT family and the FA-binding protein [111]. Patients with NLSD exhibit severe cardiomyopathy, which requires heart transplantation.…”

Section: Ldaps and Cardiomyopathymentioning

confidence: 99%

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Lipid Droplet-Associated Proteins in Cardiomyopathy

et al. 2021

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Background: The heart requires a high rate of fatty-acid oxidation (FAO) to meet its energy needs. Neutral lipids are the main source of energy for the heart and are stored in lipid droplets (LDs), which are cytosolic organelles that primarily serve to store neutral lipids and regulate cellular lipid metabolism. LD-associated proteins (LDAPs) are proteins either located on the surface of the LDs or reside in the cytosol and contribute to lipid metabolism. Therefore, abnormal cardiac lipid accumulation or FAO can alter the redox state of the heart, resulting in cardiomyopathy, a group of diseases that negatively affect the myocardial function, thereby leading to heart failure and even cardiac death. Summary: LDs, along with LDAPs, are pivotal for modulating heart lipid homeostasis. The proper cardiac development and the maintenance of its normal function depend largely on lipid homeostasis regulated by LDs and LDAPs. Overexpression or deletion of specific LDAPs can trigger myocardial dysfunction and may contribute to the development of cardiomyopathy. Extensive connections and interactions may also exist between LDAPs. Key Message: In this review, the various mechanisms involved in LDAP-mediated regulation of lipid metabolism, the association between cardiac development and lipid metabolism, as well as the role of LDAPs in cardiomyopathy progression are discussed.

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“…Both bioinformatics analysis and literature review suggested a possible role of ABHD4 mRNA in ACS. Afterwards, we retrieved data about miRNA regulation of ABHD4 mRNA and identified ( miRNA-197-5p and miRNA-221-3p ) based on both in silico data and literature review [ 28 , 29 , 30 , 31 , 32 , 33 ] that affirm that the chosen miRNAs were linked to lipid metabolism regulation as previously confirmed in ACS, targeting ABHD4 mRNA. Lastly, we aim to construct an integrated and genetically linked mRNA–miRNA–lncRNA panel to increase the chance of usefulness of the chosen panel in ACS management and novel implications for targeting ABHD enzymes in the treatment or prevention of lipid-metabolism-related disease, especially ACS.…”

Section: Introductionmentioning

confidence: 95%

ABHD4-Regulating RNA Panel: Novel Biomarkers in Acute Coronary Syndrome Diagnosis

Agwa

Elzahwy

Meteini

et al. 2021

Cells

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Background: Acute coronary syndrome (ACS) is a major cause of death all over the world. STEMI represents a type of myocardial infarction with acute ST elevation. We aimed to assess the predictive power of potential RNA panel expression in acute coronary syndrome. Method: We used in silico data analysis to retrieve RNAs related to glycerophospholipid metabolism dysregulation and specific to ACS that results in the selection of Alpha/Beta hydrolase fold domain4 (ABHD4) mRNA and its epigenetic regulators (Foxf1 adjacent noncoding developmental regulatory RNA (FENDRR) lncRNA, miRNA-221, and miRNA-197). We assessed the expression of the serum RNA panel in 68 patients with ACS, 21 patients with chest pain due to non-cardiac causes, and 21 healthy volunteers by quantitative real-time polymerase chain reaction. Results: The study data showed significant down regulation in the expression of the serum levels of FENDRR lncRNA and miRNA-221-3p by 120-fold and 22-fold in Unstable angina (UA) in comparison with healthy volunteers, and by 8.6-fold and 2-fold in ST segment elevation myocardial infarction (STEMI) patients versus UA; concomitant upregulation in the expression of ABHD4 mRNA and miRNA-197-5p by 444-fold and 10-fold in UA compared with healthy volunteers, and by 1.54-fold and 4.5-fold in STEMI versus unstable angina. Performance characteristics analysis showed that the ABHD4-regulating RNA panel were potential biomarkers for prediction of ACS. Moreover, there was a significant association between the 2 miRNAs and ABHD4 mRNA and the regulating FENDRR lncRNA. Conclusion: Collectively, ABHD4 mRNA regulating RNA panel based on putative interactions seems to be novel non-invasive biomarkers that could detect ACS early and stratify severity of the condition that could improve health outcome.

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CGI-58: Versatile Regulator of Intracellular Lipid Droplet Homeostasis

Cited by 20 publications

References 266 publications

Lipolysis: cellular mechanisms for lipid mobilization from fat stores

Lipolysis: cellular mechanisms for lipid mobilization from fat stores

Lipid Droplet-Associated Proteins in Cardiomyopathy

ABHD4-Regulating RNA Panel: Novel Biomarkers in Acute Coronary Syndrome Diagnosis

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