Molecular Pathways Leading to Cancer Cachexia

Physiology ◽  
2005 ◽  
Vol 20 (5) ◽  
pp. 340-348 ◽  
Author(s):  
Michael J. Tisdale
Keyword(s):  
Skeletal Muscle ◽  
Body Weight ◽  
Adipose Tissue ◽  
Cancer Patients ◽  
Cancer Cachexia ◽  
Host Factors ◽  
Morbidity And Mortality ◽  
Molecular Pathways

Loss of body weight in cancer patients strongly influences morbidity and mortality. Recent studies have suggested that both tumor and host factors play a major role in tissue catabolism in cachexia, leading to upregulation of degradative pathways in both skeletal muscle and adipose tissue.

scholarly journals Molecular pathways behind acquired obesity: adipose tissue and skeletal muscle multiomics in monozygotic twin pairs discordant for BMI

2021 ◽  
pp. 100226
Author(s):  
Birgitta W. van der Kolk ◽  
Sina Saari ◽  
Alen Lovric ◽  
Muhammad Arif ◽  
Marcus Alvarez ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Monozygotic Twin ◽  
Molecular Pathways

Influence of diet and exercise on skeletal muscle and visceral adipose tissue in men

1996 ◽  
Vol 81 (6) ◽  
pp. 2445-2455 ◽  
Author(s):  
Robert Ross ◽  
John Rissanen ◽  
Heather Pedwell ◽  
Jennifer Clifford ◽  
Peter Shragge
Keyword(s):  
Skeletal Muscle ◽  
Body Weight ◽  
Adipose Tissue ◽  
Visceral Adipose Tissue ◽  
Whole Body ◽  
Relative Reduction ◽  
Body Regions ◽  
Diet And Exercise ◽  
Magnetic Resonance Imaging Mri ◽  
Visceral Adipose

Ross, Robert, John Rissanen, Heather Pedwell, Jennifer Clifford, and Peter Shragge. Influence of diet and exercise on skeletal muscle and visceral adipose tissue in men. J. Appl. Physiol. 81(6): 2445–2455, 1996.—The effects of diet only (DO) and diet combined with either aerobic (DA) or resistance (DR) exercise on subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), lean tissue (LT), and skeletal muscle (SM) tissue were evaluated in 33 obese men (DO, n= 11; DA, n = 11; DR, n = 11). All tissues were measured by using a whole body multislice magnetic resonance imaging (MRI) model. Within each group, significant reductions were observed for body weight, SAT, and VAT ( P < 0.05). The reductions in body weight (∼10%) and SAT (∼25%) and VAT volume (∼35%) were not different between groups ( P > 0.05). For all treatments, the relative reduction in VAT was greater than in SAT ( P < 0.05). For the DA and DR groups only, the reduction in abdominal SAT (∼27%) was greater ( P < 0.05) than that observed for the gluteal-femoral region (∼20%). Conversely, the reduction in VAT was uniform throughout the abdomen regardless of treatment ( P > 0.05). MRI-LT and MRI-SM decreased both in the upper and lower body regions for the DO group alone ( P < 0.05). Peak O2 uptake (liters) was significantly improved (∼14%) in the DA group as was muscular strength (∼20%) in the DR group ( P< 0.01). These findings indicate that DA and DR result in a greater preservation of MRI-SM, mobilization of SAT from the abdominal region, by comparison with the gluteal-femoral region, and improved functional capacity when compared with DO in obese men.

scholarly journals The Adipokines in Cancer Cachexia

2020 ◽  
Vol 21 (14) ◽  
pp. 4860 ◽  
Author(s):  
Michele Mannelli ◽  
Tania Gamberi ◽  
Francesca Magherini ◽  
Tania Fiaschi
Keyword(s):  
Insulin Resistance ◽  
Cardiovascular Disease ◽  
Skeletal Muscle ◽  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
Cancer Cachexia ◽  
Muscle Wasting ◽  
Therapeutic Strategies ◽  
Skeletal Muscle Wasting ◽  
Circulating Levels

Cachexia is a devastating pathology induced by several kinds of diseases, including cancer. The hallmark of cancer cachexia is an extended weight loss mainly due to skeletal muscle wasting and fat storage depletion from adipose tissue. The latter exerts key functions for the health of the whole organism, also through the secretion of several adipokines. These hormones induce a plethora of effects in target tissues, ranging from metabolic to differentiating ones. Conversely, the decrease of the circulating level of several adipokines positively correlates with insulin resistance, metabolic syndrome, diabetes, and cardiovascular disease. A lot of findings suggest that cancer cachexia is associated with changed secretion of adipokines by adipose tissue. In agreement, cachectic patients show often altered circulating levels of adipokines. This review reported the findings of adipokines (leptin, adiponectin, resistin, apelin, and visfatin) in cancer cachexia, highlighting that to study in-depth the involvement of these hormones in this pathology could lead to the development of new therapeutic strategies.

scholarly journals Molecular pathways leading to loss of skeletal muscle mass in cancer cachexia – can findings from animal models be translated to humans?

BMC Cancer ◽  
2016 ◽  
Vol 16 (1) ◽  
Author(s):  
Tara C. Mueller ◽  
Jeannine Bachmann ◽  
Olga Prokopchuk ◽  
Helmut Friess ◽  
Marc E. Martignoni
Keyword(s):  
Skeletal Muscle ◽  
Animal Models ◽  
Muscle Mass ◽  
Skeletal Muscle Mass ◽  
Cancer Cachexia ◽  
Molecular Pathways

Changes in body weight, skeletal muscle and adipose tissue after gastrectomy: a comparison between proximal gastrectomy and total gastrectomy

2019 ◽  
Vol 89 (1-2) ◽  
pp. 79-83 ◽  
Author(s):  
Raito Asaoka ◽  
Tomoyuki Irino ◽  
Rie Makuuchi ◽  
Yutaka Tanizawa ◽  
Etsuro Bando ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Body Weight ◽  
Adipose Tissue ◽  
Total Gastrectomy ◽  
Proximal Gastrectomy

scholarly journals The Extract of Arctium lappa L. Fruit (Arctii Fructus) Improves Cancer-Induced Cachexia by Inhibiting Weight Loss of Skeletal Muscle and Adipose Tissue

Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3195
Author(s):  
Yo-Han Han ◽  
Jeong-Geon Mun ◽  
Hee Dong Jeon ◽  
Dae Hwan Yoon ◽  
Byung-Min Choi ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Weight Loss ◽  
Adipose Tissue ◽  
Cancer Cachexia ◽  
Uncoupling Protein ◽  
Body Weight Loss ◽  
In Vivo Experiments ◽  
Wasting Syndrome

Background: Cachexia induced by cancer is a systemic wasting syndrome and it accompanies continuous body weight loss with the exhaustion of skeletal muscle and adipose tissue. Cancer cachexia is not only a problem in itself, but it also reduces the effectiveness of treatments and deteriorates quality of life. However, effective treatments have not been found yet. Although Arctii Fructus (AF) has been studied about several pharmacological effects, there were no reports on its use in cancer cachexia. Methods: To induce cancer cachexia in mice, we inoculated CT-26 cells to BALB/c mice through subcutaneous injection and intraperitoneal injection. To mimic cancer cachexia in vitro, we used conditioned media (CM), which was CT-26 colon cancer cells cultured medium. Results: In in vivo experiments, AF suppressed expression of interleukin (IL)-6 and atrophy of skeletal muscle and adipose tissue. As a result, the administration of AF decreased mortality by preventing weight loss. In adipose tissue, AF decreased expression of uncoupling protein 1 (UCP1) by restoring AMP-activated protein kinase (AMPK) activation. In in vitro model, CM increased muscle degradation factors and decreased adipocytes differentiation factors. However, these tendencies were ameliorated by AF treatment in C2C12 myoblasts and 3T3-L1 cells. Conclusion: Taken together, our study demonstrated that AF could be a therapeutic supplement for patients suffering from cancer cachexia.

Growth differentiation factor 15 (GDF-15) inhibition to increase muscle mass and function in cancer cachexia.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15633-e15633
Author(s):  
Matthew Peloquin ◽  
Brianna LaCarubba ◽  
Stephanie Joaqium ◽  
Gregory Weber ◽  
John Stansfield ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Body Weight ◽  
Muscle Mass ◽  
Muscle Function ◽  
Skeletal Muscle Mass ◽  
Cancer Cachexia ◽  
Tumor Model ◽  
Growth Differentiation Factor 15 ◽  
Myostatin Inhibition ◽  
And Function

e15633 Background: Almost half of cancer deaths are attributed to cancers most frequently associated with cachexia. Cachexia is a complex metabolic disease characterized by anorexia and unintentional weight loss. Skeletal muscle depletion has been recognized as a key feature of the disease, however muscle anabolic therapies have not been successful, suggesting that treatments that target multiple aspects of the disease will be most effective. Growth differentiation factor 15 (GDF-15) is a cytokine that induces anorexia and weight loss and is associated with cachexia in cancer patients. In preclinical cancer cachexia models, GDF-15 inhibition is sufficient to normalize food intake and body weight, including skeletal muscle mass. However, it remains to be determined whether the increased skeletal muscle mass also results in restoration of muscle function. Therefore, we examined the effect of GDF-15 inhibition on muscle mass and function in mouse models of cancer cachexia in comparison with myostatin inhibition, an established muscle anabolic pathway. Methods: Cachectic mouse tumor models were established with subcutaneous implantation of tumor cell lines reported to be GDF-15-dependent; mouse renal cell carcinoma (RENCA) and human ovarian cancer (TOV-21G) cell lines. Mice were treated with anti-GDF-15 (mAB2) or anti-myostatin (RK35) monoclonal antibodies and skeletal muscle function was assessed in vivo via maximum force, maximum rate of contraction and half relax time. In the RENCA tumor model, GDF-15 inhibition fully restored body weight and skeletal muscle mass whereas myostatin inhibition showed only a modest effect. Results: Consistent with the muscle mass improvement, GDF-15 inhibition dramatically increased functional muscle endpoints compared to the partial effect of myostatin inhibition. Interestingly, in the TOV-21G tumor model GDF-15 inhibition only partially restored body weight, however skeletal muscle mass and muscle function were completely normalized. Consistent with the functional assessment, GDF-15 inhibition in the RENCA tumor model decreased the expression of several catabolic genes (i.e. Trim63, Fbxo32, Myh7 and Myh2). The GDF-15 effect is likely to be secondary to the reversal of anorexia since wildtype mice pair-fed to Fc-GDF-15-treated mice demonstrated equivalent muscle mass loss. Conclusions: Taken together these data suggest that GDF-15 inhibition holds potential as an effective therapeutic approach to alleviate multiple aspects of cachexia.

scholarly journals A combination of exercise and capsinoid supplementation additively suppresses diet-induced obesity by increasing energy expenditure in mice

2015 ◽  
Vol 308 (4) ◽  
pp. E315-E323 ◽  
Author(s):  
Kana Ohyama ◽  
Yoshihito Nogusa ◽  
Katsuya Suzuki ◽  
Kosaku Shinoda ◽  
Shingo Kajimura ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Body Weight ◽  
Adipose Tissue ◽  
Weight Gain ◽  
Energy Expenditure ◽  
Body Weight Gain ◽  
Whole Body ◽  
Voluntary Running ◽  
Running Wheel Exercise ◽  
Body Energy

Exercise effectively prevents the development of obesity and obesity-related diseases such as type 2 diabetes. Capsinoids (CSNs) are capsaicin analogs found in a nonpungent pepper that increase whole body energy expenditure. Although both exercise and CSNs have antiobesity functions, the effectiveness of exercise with CSN supplementation has not yet been investigated. Here, we examined whether the beneficial effects of exercise could be further enhanced by CSN supplementation in mice. Mice were randomly assigned to four groups: 1) high-fat diet (HFD, Control), 2) HFD containing 0.3% CSNs, 3) HFD with voluntary running wheel exercise (Exercise), and 4) HFD containing 0.3% CSNs with voluntary running wheel exercise (Exercise + CSN). After 8 wk of ingestion, blood and tissues were collected and analyzed. Although CSNs significantly suppressed body weight gain under the HFD, CSN supplementation with exercise additively decreased body weight gain and fat accumulation and increased whole body energy expenditure compared with exercise alone. Exercise together with CSN supplementation robustly improved metabolic profiles, including the plasma cholesterol level. Furthermore, this combination significantly prevented diet-induced liver steatosis and decreased the size of adipocyte cells in white adipose tissue. Exercise and CSNs significantly increased cAMP levels and PKA activity in brown adipose tissue (BAT), indicating an increase of lipolysis. Moreover, they significantly activated both the oxidative phosphorylation gene program and fatty acid oxidation in skeletal muscle. These results indicate that CSNs efficiently promote the antiobesity effect of exercise, in part by increasing energy expenditure via the activation of fat oxidation in skeletal muscle and lipolysis in BAT.

Upregulation of uncoupling proteins by oral administration of capsiate, a nonpungent capsaicin analog

2003 ◽  
Vol 95 (6) ◽  
pp. 2408-2415 ◽  
Author(s):  
Yoriko Masuda ◽  
Satoshi Haramizu ◽  
Kasumi Oki ◽  
Koichiro Ohnuki ◽  
Tatsuo Watanabe ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Body Weight ◽  
Adipose Tissue ◽  
Single Dose ◽  
Thyroid Hormones ◽  
Brown Adipose Tissue ◽  
Uncoupling Proteins ◽  
Brown Adipose ◽  
Pepper Cultivar ◽  
Ucp2 Mrna

Capsiate is a nonpungent capsaicin analog, a recently identified principle of the nonpungent red pepper cultivar CH-19 Sweet. In the present study, we report that 2-wk treatment of capsiate increased metabolic rate and promoted fat oxidation at rest, suggesting that capsiate may prevent obesity. To explain these effects, at least in part, we examined uncoupling proteins (UCPs) and thyroid hormones. UCPs and thyroid hormones play important roles in energy expenditure, the maintenance of body weight, and thermoregulation. Two-week treatment of capsiate increased the levels of UCP1 protein and mRNA in brown adipose tissue and UCP2 mRNA in white adipose tissue. This dose of capsiate did not change serum triiodothyronine or thyroxine levels. A single dose of capsiate temporarily raised both UCP1 mRNA in brown adipose tissue and UCP3 mRNA in skeletal muscle. These results suggest that UCP1 and UCP2 may contribute to the promotion of energy metabolism by capsiate, but that thyroid hormones do not.

scholarly journals Cancer Cachexia and Related Metabolic Dysfunction

2020 ◽  
Vol 21 (7) ◽  
pp. 2321 ◽  
Author(s):  
Guilherme Wesley Peixoto da Fonseca ◽  
Jerneja Farkas ◽  
Eva Dora ◽  
Stephan von Haehling ◽  
Mitja Lainscak
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Physical Function ◽  
Nutritional Support ◽  
Cancer Cachexia ◽  
Metabolic Dysfunction ◽  
Pharmacological Agents ◽  
Patients With Cancer ◽  
Reasonable Approach ◽  
Body Compartments

Cancer cachexia is a complex multifactorial syndrome marked by a continuous depletion of skeletal muscle mass associated, in some cases, with a reduction in fat mass. It is irreversible by nutritional support alone and affects up to 74% of patients with cancer—dependent on the underlying type of cancer—and is associated with physical function impairment, reduced response to cancer-related therapy, and higher mortality. Organs, like muscle, adipose tissue, and liver, play an important role in the progression of cancer cachexia by exacerbating the pro- and anti-inflammatory response initially activated by the tumor and the immune system of the host. Moreover, this metabolic dysfunction is produced by alterations in glucose, lipids, and protein metabolism that, when maintained chronically, may lead to the loss of skeletal muscle and adipose tissue. Although a couple of drugs have yielded positive results in increasing lean body mass with limited impact on physical function, a single therapy has not lead to effective treatment of this condition. Therefore, a multimodal intervention, including pharmacological agents, nutritional support, and physical exercise, may be a reasonable approach for future studies to better understand and prevent the wasting of body compartments in patients with cancer cachexia.

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