Cachexia, a Systemic Disease beyond Muscle Atrophy

Wyart, Elisabeth; Bindels, Laure B.; Mina, Erica; Menga, Alessio; Stanga, Serena; Porporato, Paolo E.

doi:10.3390/ijms21228592

Cited by 29 publications

(35 citation statements)

References 154 publications

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“…The mechanisms as well as the significance of skeletal muscle wasting and fat loss in cancer cachexia have been identified. However, whether bone metastasis-free tumor growth is associated with bone loss in cancer cachexia remains unclear [ 60 ]. Importantly, muscle loss is associated with bone dysfunction, which reduces mobility and quality of life [ 48 , 60 ] and this association was also found in cancer patients [ 61 ].…”

Section: Discussionmentioning

confidence: 99%

“…However, whether bone metastasis-free tumor growth is associated with bone loss in cancer cachexia remains unclear [ 60 ]. Importantly, muscle loss is associated with bone dysfunction, which reduces mobility and quality of life [ 48 , 60 ] and this association was also found in cancer patients [ 61 ]. Therefore, it is important to determine whether tumor growth is associated with the occurrence of bone loss in cancer cachexia and identify mechanisms underlying bone loss.…”

Section: Discussionmentioning

confidence: 99%

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Bone Marrow Homeostasis Is Impaired via JAK/STAT and Glucocorticoid Signaling in Cancer Cachexia Model

Choi

Park

et al. 2021

Cancers

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Cancer cachexia is a multifactorial systemic inflammation disease caused by complex interactions between the tumor and host tissues via soluble factors. However, whether cancer cachexia affects the bone marrow, in particular the hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs), remains unclear. Here, we investigated the bone marrow and bone in a cancer cachexia animal model generated by transplanting Lewis lung carcinoma cells. The number of bone marrow mononuclear cells (BM-MNCs) started to significantly decrease in the cancer cachectic animal model prior to the discernable loss of muscle and fat. This decrease in BM-MNCs was associated with myeloid skewing in the circulation and the expansion of hematopoietic progenitors in the bone marrow. Bone loss occurred in the cancer cachexia animal model and accompanied the decrease in the bone marrow MSCs that play important roles in both supporting HSCs and maintaining bone homeostasis. Glucocorticoid signaling mediated the decrease in bone marrow MSCs in the cancer cachectic environment. The cancer cachexia environment also skewed the differentiation of the bone marrow MSCs toward adipogenic fate via JAK/STAT as well as glucocorticoid signaling. Our results suggest that the bone loss induced in cancer cachexia is associated with the depletion and the impaired differentiation capacity of the bone marrow MSCs.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Bone Marrow Homeostasis Is Impaired via JAK/STAT and Glucocorticoid Signaling in Cancer Cachexia Model

Choi

Park

et al. 2021

Cancers

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“…Muscle loss in cachexia is due to both reduced protein synthesis and increased catabolism (proteolysis) due to multiple factors including reduced oral intake, high levels of inflammation, tumor-mediated effects, low physical activity, and endocrine and metabolic disturbances [96]. Some studies have demonstrated that CR can have an effect on the majority of these mechanisms; however, PLA-controlled studies have shown mixed results.…”

Section: Potential Of Creatine Supplementation For Cachexiamentioning

confidence: 99%

Current Evidence and Possible Future Applications of Creatine Supplementation for Older Adults

et al. 2021

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Sarcopenia, defined as age-related reduction in muscle mass, strength, and physical performance, is associated with other age-related health conditions such as osteoporosis, osteosarcopenia, sarcopenic obesity, physical frailty, and cachexia. From a healthy aging perspective, lifestyle interventions that may help overcome characteristics and associated comorbidities of sarcopenia are clinically important. One possible intervention is creatine supplementation (CR). Accumulating research over the past few decades shows that CR, primarily when combined with resistance training (RT), has favourable effects on aging muscle, bone and fat mass, muscle and bone strength, and tasks of physical performance in healthy older adults. However, research is very limited regarding the efficacy of CR in older adults with sarcopenia or osteoporosis and no research exists in older adults with osteosarcopenia, sarcopenic obesity, physical frailty, or cachexia. Therefore, the purpose of this narrative review is (1) to evaluate and summarize current research involving CR, with and without RT, on properties of muscle and bone in older adults and (2) to provide a rationale and justification for future research involving CR in older adults with osteosarcopenia, sarcopenic obesity, physical frailty, or cachexia.

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“…Hence, to heighten the awareness of conditions potentially inducing cachexia, it is essential to speed up the identification of novel diagnostic markers to improve the diagnosis of cachexia. The onset of cachexia has been proven to occur before evident weight loss and muscle wasting; thus, it is critical to search for adipose-related biomarkers to facilitate early diagnosis and an appropriate therapy response [ 38 ]. It has been suggested that non-coding RNAs, with their conserved structure and stable expression in the cytoplasm, are ideal biomarkers [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

Novel noncoding RNA CircPTK2 regulates lipolysis and adipogenesis in cachexia

Ding

Sun

Han

et al. 2021

Molecular Metabolism

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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, luciferase reporter assay, RNA immunoprecipitation, and fluorescent in situ hybridization were 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.

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Cachexia, a Systemic Disease beyond Muscle Atrophy

Cited by 29 publications

References 154 publications

Bone Marrow Homeostasis Is Impaired via JAK/STAT and Glucocorticoid Signaling in Cancer Cachexia Model

Bone Marrow Homeostasis Is Impaired via JAK/STAT and Glucocorticoid Signaling in Cancer Cachexia Model

Current Evidence and Possible Future Applications of Creatine Supplementation for Older Adults

Novel noncoding RNA CircPTK2 regulates lipolysis and adipogenesis in cachexia

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