Cover Story Current Issue

White adipose tissue (WAT) is a complex organ that plays a central role in systemic energy balance through its interrelated metabolic, endocrine, and immune functions. Adipocytes, the parenchymal cells of adipose tissue, have diverse functions that include storage and mobilization of lipids. They also release endocrine signals that report energy status to the brain, regulating metabolic functions in peripheral organs. Importantly, the metabolic character of white adipocytes is flexible, with cells capable of assuming distinct anabolic and catabolic/thermogenic phenotypes, often within the same adipose tissue depot

Elizabeth A. Rondini, Vanesa D. Ramseyer, Rayanne B. Burl, Roger Pique-Regi, James G. Granneman

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Current Issue

Novel noncoding RNA CircPTK2 regulates lipolysis and adipogenesis in cachexia

Zuoyou Ding, Diya Sun, Jun Han, Lei Shen, ... Guohao Wu

Objective

Cancer-associated cachexia is a devastating pathological disorder characterized by skeletal muscle wasting and fat storage depletion. Circular RNA, a newly discovered class of noncoding RNAs with important roles in regulating lipid metabolism, has not been fully understood in the pathology of cachexia. We aimed to identify circular RNAs that are upregulated in adipose tissues from cachectic patients and explore their function and mechanism in lipid metabolism.

Methods

Whole transcriptome RNA sequencing was used to screen for differentially expressed circRNAs. Quantitative reverse transcription PCR was applied to detect the expression level of circPTK2 in adipose tissues. The diagnostic value of circPTK2 was evaluated in adipose tissues from patients with and without cachexia. Then, function experiments in vitro and in vivo were performed to evaluate the effects of circPTK2 on lipolysis and adipogenesis. Mechanistically, luciferasereporter assay, RNA immunoprecipitation, and fluorescent in situ hybridizationwere performed to confirm the interaction between circPTK2 and miR-182-5p in adipocytes.

Results

We detected 66 differentially expressed circular RNA candidates and proved that circPTK2 was upregulated in adipose tissues from cachectic patients. Then we identified that circPTK2 was closely related to the pathological process of cachexia and could be used as a diagnostic marker. Mechanistically, circPTK2 bound competitively to miR-182-5p and abrogated the suppression on its target gene JAZF1, which finally led to promotion of lipolysis and inhibition of adipogenesis. In vivo experiments demonstrated that overexpression of circPTK2 inhibited adipogenesis and enhanced lipolysis.

Conclusions

Our findings reveal the novel role of circPTK2 in promoting lipolysis and reducing adipogenesis via a ceRNA mechanism and provide a potential diagnostic biomarker and therapeutic target for cancer-associated cachexia.

Novel noncoding RNA CircPTK2 regulates lipolysis and adipogenesis in cachexia

Zuoyou Ding, Diya Sun, Jun Han, Lei Shen, ... Guohao Wu

Objective

Cancer-associated cachexia is a devastating pathological disorder characterized by skeletal muscle wasting and fat storage depletion. Circular RNA, a newly discovered class of noncoding RNAs with important roles in regulating lipid metabolism, has not been fully understood in the pathology of cachexia. We aimed to identify circular RNAs that are upregulated in adipose tissues from cachectic patients and explore their function and mechanism in lipid metabolism.

Methods

Whole transcriptome RNA sequencing was used to screen for differentially expressed circRNAs. Quantitative reverse transcription PCR was applied to detect the expression level of circPTK2 in adipose tissues. The diagnostic value of circPTK2 was evaluated in adipose tissues from patients with and without cachexia. Then, function experiments in vitro and in vivo were performed to evaluate the effects of circPTK2 on lipolysis and adipogenesis. Mechanistically, luciferasereporter assay, RNA immunoprecipitation, and fluorescent in situ hybridizationwere performed to confirm the interaction between circPTK2 and miR-182-5p in adipocytes.

Results

We detected 66 differentially expressed circular RNA candidates and proved that circPTK2 was upregulated in adipose tissues from cachectic patients. Then we identified that circPTK2 was closely related to the pathological process of cachexia and could be used as a diagnostic marker. Mechanistically, circPTK2 bound competitively to miR-182-5p and abrogated the suppression on its target gene JAZF1, which finally led to promotion of lipolysis and inhibition of adipogenesis. In vivo experiments demonstrated that overexpression of circPTK2 inhibited adipogenesis and enhanced lipolysis.

Conclusions

Our findings reveal the novel role of circPTK2 in promoting lipolysis and reducing adipogenesis via a ceRNA mechanism and provide a potential diagnostic biomarker and therapeutic target for cancer-associated cachexia.

2020 impact factor: 7.4

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