Fat Wasting Is Damaging: Role of Adipose Tissue in Cancer-Associated Cachexia

Sun, Xiaoting; Feng, Xiaogang; Wu, Xiaojing; Lu, Yongtian; Chen, Kaihong; Ye, Ying

doi:10.3389/fcell.2020.00033

Cited by 47 publications

(36 citation statements)

References 98 publications

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“…Adipogenesis, the formation of adipocytes from stem cells, is important for energy homeostasis and is involved in processing triglycerol, the largest energy reserve in the body. 17 IL-1β inhibits adipogenesis as suggested by the finding that potential of adipogenic progenitor cells isolated from patients with DMD are significantly reduced when co-cultured with IL-1β-secreting macrophages. 18 We showed that anakinra normalized fat content in CKD mice (Figure 2E).…”

Section: Discussionmentioning

confidence: 99%

The role of IL-1 in adipose browning and muscle wasting in CKD-associated cachexia

Cheung

Zheng

Sheng

et al. 2021

Preprint

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Cytokines such as IL-6, TNF-αand IL-1β trigger inflammatory cascades which may play a role in the pathogenesis of chronic kidney disease (CKD)-associated cachexia. CKD was induced by 5/6 nephrectomy in mice. We studied energy homeostasis in Il1β -/-/CKD, Il6-/-/CKD and Tnfα -/-/CKD mice and compared with wild type (WT)/CKD controls. Parameters of cachexia phenotype were completely normalized in Il1β -/-/CKD mice but were only partially rescued in Il6-/-/CKD and Tnfα -/-/CKD mice. We tested the effects of anakinra, an IL-1 receptor antagonist, on CKD-associated cachexia. WT/CKD mice were treated with anakinra (2.5 mg.kg.day, IP) or saline for 6 weeks and compared with WT/sham controls. Anakinra normalized food intake and weight gain, fat and lean mass content, metabolic rate and muscle function, and also attenuated molecular perturbations of energy homeostasis in adipose tissue and muscle in WT/CKD mice. Anakinra attenuated browning of white adipose tissue in WT/CKD mice. Moreover, anakinra normalized gastrocnemius weight and fiber size as well as attenuated muscle fat infiltration in WT/CKD mice. This was accompanied by correcting the increased muscle wasting signaling pathways while promoting the decreased myogenesis process in gastrocnemius of WT/CKD mice. We performed qPCR analysis for the top 20 differentially expressed muscle genes previously identified via RNAseq analysis in WT/CKD mice versus controls. Importantly, 17 differentially expressed muscle genes were attenuated in anakinra treated WT/CKD mice. In conclusion, IL-1 receptor antagonism may represent a novel targeted treatment for adipose tissue browning and muscle wasting in CKD.

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Section: Discussionmentioning

confidence: 99%

The role of IL-1 in adipose browning and muscle wasting in CKD-associated cachexia

Cheung

Zheng

Sheng

et al. 2021

Preprint

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“…According to morphologic modifications, decreased lipid content and a proinflammatory phenotype, cachectic adipocytes are similar to TAAs (Rybinska et al, 2020). As recently demonstrated, the downregulation of adipogenic and lipogenic genes is affected early in AT, resulting in lipolysis and AT remodeling during CC (Batista et al, 2013;Sun et al, 2020). Also, CC is associated with fibrosis and inflammatory cell infiltration in SAT (Batista et al, 2016), while VAT shows a low lipolysis rate in the early stage of CC and a low de novo lipogenesis rate in later stages.…”

Section: Tumor-induced Adipose Tissue Remodelingmentioning

confidence: 86%

Adipogenesis in Different Body Depots and Tumor Development

Trivanović¹,

Petrinović

Djordjević

et al. 2020

Front. Cell Dev. Biol.

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Adipose tissue (AT) forms depots at different anatomical locations throughout the body, being in subcutaneous and visceral regions, as well as the bone marrow. These ATs differ in the adipocyte functional profile, their insulin sensitivity, adipokines' production, lipolysis, and response to pathologic conditions. Despite the recent advances in lineage tracing, which have demonstrated that individual adipose depots are composed of adipocytes derived from distinct progenitor populations, the cellular and molecular dissection of the adipose clonogenic stem cell niche is still a great challenge. Additional complexity in AT regulation is associated with tumor-induced changes that affect adipocyte phenotype. As an integrative unit of cell differentiation, AT microenvironment regulates various phenotype outcomes of differentiating adipogenic lineages, which consequently may contribute to the neoplastic phenotype manifestations. Particularly interesting is the capacity of AT to impose and support the aberrant potency of stem cells that accompanies tumor development. In this review, we summarize the current findings on the communication between adipocytes and their progenitors with tumor cells, pointing out to the coexistence of healthy and neoplastic stem cell niches developed during tumor evolution. We also discuss tumor-induced adaptations in mature adipocytes and the involvement of alternative differentiation programs.

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“…The presence of the tumor may have affected the food intake of the isolated OSCC rats that in turn showed larger tumors when compared to control rats. Furthermore, this loss of body weight may be derived from the tumor-induced cachexia [ 48 ]. Tumor-induced cachexia achieves up to 80% of the advanced-stage cancer patients, including those with head and neck cancer malignancies [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

“…These patients exhibit significant weight loss and some of them report concerns about eating, especially when receiving palliative care [ 49 ]. Although the food consumption during carcinogenesis period was not measured in the current study, isolated rats could have lost body weight due to a lower food intake and by losing adipose tissue and skeletal muscle mass, required in the increased metabolic waste [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

Social isolation stress facilitates chemically induced oral carcinogenesis

et al. 2021

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Social isolation has affected a large number of people and may lead to impairment of physical and mental health. Although stress resulting from social isolation may increase cancer progression, its interference on tumorigenesis is poorly known. In this study, we used a preclinical model to evaluate the effects of social isolation stress on chemically induced oral carcinogenesis. Sixty-two 21-day-old male Wistar rats were divided into isolated and grouped groups. After 90 days of age, the rats from both groups underwent oral carcinogenesis with 4-nitroquinoline 1-oxide (4NQO) for 20 weeks. All rats were assessed for depressive-like behavior and euthanized for oral squamous cell carcinoma (OSCC) diagnosis and measurement of inflammatory mediators in the tumor microenvironment. Social isolation stress increased the OSCC occurrence by 20.4% when compared to control. Isolated rats also showed higher tumor volume and cachexia than the grouped rats. Social isolation did not induce changes in the depressive-like behavior after carcinogenic induction. Tumors from stressed rats had increased levels of the inflammatory mediators, TNF-alpha, IL1-beta and MCP-1. The concentrations of TNF-alpha and MCP-1 were significantly increased in the large tumors from isolated animals. Higher tumor levels of TNF-alpha, IL-6, IL1-beta and MCP-1 were positively correlated with OSCC growth. This study provides the first evidence that social isolation stress may facilitate OSCC occurrence and tumor progression, an event accompanied by increased local levels of inflammatory mediators.

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Fat Wasting Is Damaging: Role of Adipose Tissue in Cancer-Associated Cachexia

Cited by 47 publications

References 98 publications

The role of IL-1 in adipose browning and muscle wasting in CKD-associated cachexia

The role of IL-1 in adipose browning and muscle wasting in CKD-associated cachexia

Adipogenesis in Different Body Depots and Tumor Development

Social isolation stress facilitates chemically induced oral carcinogenesis

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