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 Exercise as an anti-inflammatory therapy for cancer cachexia: a focus on interleukin-6 regulation

2020 ◽  
Vol 318 (2) ◽  
pp. R296-R310 ◽  
Author(s):  
Hélène N. Daou
Keyword(s):  
Skeletal Muscle ◽  
Systemic Inflammation ◽  
Cancer Cachexia ◽  
Muscle Wasting ◽  
Skeletal Muscle Atrophy ◽  
Ampk Signaling ◽  
Skeletal Muscle Wasting ◽  
Skeletal Muscle Loss ◽  
Anti Inflammatory ◽  
Tumor Growth And Metastasis

Cancer cachexia is a complicated disorder of extreme, progressive skeletal muscle wasting. It is directed by metabolic alterations and systemic inflammation dysregulation. Numerous studies have demonstrated that increased systemic inflammation promotes this type of cachexia and have suggested that cytokines are implicated in the skeletal muscle loss. Exercise is firmly established as an anti-inflammatory therapy that can attenuate or even reverse the process of muscle wasting in cancer cachexia. The interleukin IL-6 is generally considered to be a key player in the development of the microenvironment of malignancy; it promotes tumor growth and metastasis by acting as a bridge between chronic inflammation and cancerous tissue and it also induces skeletal muscle atrophy and protein breakdown. Paradoxically, a beneficial role for IL-6 has also been identified recently, and that is its status as a “founding member” of the myokine class of proteins. Skeletal muscle is an important source of circulating IL-6 in people who participate in exercise training. IL-6 acts as an anti-inflammatory myokine by inhibiting TNFα and improving glucose uptake through the stimulation of AMPK signaling. This review discusses the action of IL-6 in skeletal muscle tissue dysfunction and the role of IL-6 as an “exercise factor” that modulates the immune system. This review also sheds light on the main considerations related to the treatment of muscle wasting in cancer cachexia.

scholarly journals JNK signaling contributes to skeletal muscle wasting and protein turnover in pancreatic cancer cachexia

2020 ◽  
Vol 491 ◽  
pp. 70-77 ◽  
Author(s):  
Scott E. Mulder ◽  
Aneesha Dasgupta ◽  
Ryan J. King ◽  
Jaime Abrego ◽  
Kuldeep S. Attri ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Pancreatic Cancer ◽  
Protein Turnover ◽  
Cancer Cachexia ◽  
Muscle Wasting ◽  
Jnk Signaling ◽  
Skeletal Muscle Wasting

scholarly journals Reduced Levels of Circulating 7α-Hydroxy-Dehydroepiandrosterone in Treated Adolescent Obese Patients

2014 ◽  
pp. 95-101
Author(s):  
L. MÁČOVÁ ◽  
M. BIČÍKOVÁ ◽  
H. ZAMRAZILOVÁ ◽  
M. HILL ◽  
H. KAZIHNITKOVÁ ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Body Mass Index ◽  
Adipose Tissue ◽  
Hydroxysteroid Dehydrogenase ◽  
Obese Patients ◽  
Significant Difference ◽  
Before And After ◽  
Reductive Treatment ◽  
Circulating Levels

Elevated levels of glucocorticoids lead to the development of obesity and metabolic syndrome. Local glucocorticoid levels are regulated through the enzyme 11β-hydroxysteroid dehydrogenase 1 (11β-HSD 1), an enzyme that regenerates active cortisol from inert cortisone. Increased expression of 11β-HSD 1 in adipose tissue promotes higher body mass index (BMI), insulin resistance, hypertension, and dyslipidemia. Human 11β-HSD 1 is also responsible for inter-conversion of 7-hydroxylate metabolites of dehydroepiandrosterone (7-OH-DHEA) to their 7-oxo-form. To better understanding the mechanism of the action, we focused on 7-OH- and 7-oxo-DHEA, and their circulating levels during the reductive treatment in adolescent obese patients. We determined plasma levels of 7α-OH-DHEA, 7β-OH-DHEA, and 7-oxo-DHEA in 55 adolescent patients aged 13.04-15.67 years, BMI greater than 90th percentile. Samples were collected before and after one month of reductive therapy. Circulating levels of 7α-OH-DHEA decreased during the reductive therapy from 1.727 (1.614; 1.854, transformed mean with 95 % confidence interval) to 1.530 nmol/l (1.435; 1.637, p<0.05) in girls and from 1.704 (1.583; 1.842) to 1.540 nmol/l (1.435; 1.659, p<0.05) in boys. With regard to the level of 7-oxo-DHEA, a significant reduction from 1.132 (1.044; 1.231) to 0.918 nmol/l (0.844; 1.000, p<0.05) was found after the treatment, but only in boys. No significant difference in 7β-OH-DHEA levels was observed. In conclusions, diminished levels of 7α-OH-DHEA indicate its possible effect on activity of 11β-HSD 1. Further studies are necessary to clarify whether competitive substrates for 11β-HSD 1 such as 7α-OH-DHEA could inhibit production of glucocorticoids and may be involved in metabolic processes leading to reduction of obesity.

scholarly journals Insights Into the Controversial Aspects of Adiponectin in Cardiometabolic Disorders

2020 ◽  
Vol 52 (10) ◽  
pp. 695-707
Author(s):  
Emilio Antonio Francischetti ◽  
Rômulo Sperduto Dezonne ◽  
Cláudia Maria Pereira ◽  
Cyro José de Moraes Martins ◽  
Bruno Miguel Jorge Celoria ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Metabolic Syndrome ◽  
Type 2 Diabetes Mellitus ◽  
Overweight And Obesity ◽  
Adiponectin Receptors ◽  
Circulating Levels

AbstractIn 2016, the World Health Organization estimated that more than 1.9 billion adults were overweight or obese. This impressive number shows that weight excess is pandemic. Overweight and obesity are closely associated with a high risk of comorbidities, such as insulin resistance and its most important outcomes, including metabolic syndrome, type 2 diabetes mellitus, and cardiovascular disease. Adiponectin has emerged as a salutary adipocytokine, with insulin-sensitizing, anti-inflammatory, and cardiovascular protective properties. However, under metabolically unfavorable conditions, visceral adipose tissue-derived inflammatory cytokines might reduce the transcription of the adiponectin gene and consequently its circulating levels. Low circulating levels of adiponectin are negatively associated with various conditions, such as insulin resistance, type 2 diabetes mellitus, metabolic syndrome, and cardiovascular disease. In contrast, several recent clinical trials and meta-analyses have reported high circulating adiponectin levels positively associated with cardiovascular mortality and all-cause mortality. These results are biologically intriguing and counterintuitive, and came to be termed “the adiponectin paradox”. Adiponectin paradox is frequently associated with adiponectin resistance, a concept related with the downregulation of adiponectin receptors in insulin-resistant states. We review this contradiction between the apparent role of adiponectin as a health promoter and the recent evidence from Mendelian randomization studies indicating that circulating adiponectin levels are an unexpected predictor of increased morbidity and mortality rates in several clinical conditions. We also critically review the therapeutic perspective of synthetic peptide adiponectin receptors agonist that has been postulated as a promising alternative for the treatment of metabolic syndrome and type 2 diabetes mellitus.

scholarly journals Mitofusin-2 prevents skeletal muscle wasting in cancer cachexia

2016 ◽  
Vol 12 (5) ◽  
pp. 4013-4020 ◽  
Author(s):  
Qiu-Lei Xi ◽  
Bo Zhang ◽  
Yi Jiang ◽  
Hai-Sheng Zhang ◽  
Qing-Yang Meng ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Cancer Cachexia ◽  
Muscle Wasting ◽  
Mitofusin 2 ◽  
Skeletal Muscle Wasting

scholarly journals Myostatin is a novel tumoral factor that induces cancer cachexia

2012 ◽  
Vol 446 (1) ◽  
pp. 23-36 ◽  
Author(s):  
Sudarsanareddy Lokireddy ◽  
Isuru Wijerupage Wijesoma ◽  
Sabeera Bonala ◽  
Meng Wei ◽  
Siu Kwan Sze ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Growth Factor ◽  
Skeletal Muscles ◽  
Cancer Cachexia ◽  
Muscle Wasting ◽  
Transforming Growth Factor ◽  
C2c12 Myotubes ◽  
E3 Ligases ◽  
Molecular Features ◽  
Skeletal Muscle Wasting

Humoral and tumoral factors collectively promote cancer-induced skeletal muscle wasting by increasing protein degradation. Although several humoral proteins, namely TNFα (tumour necrosis factor α) and IL (interleukin)-6, have been shown to induce skeletal muscle wasting, there is a lack of information regarding the tumoral factors that contribute to the atrophy of muscle during cancer cachexia. Therefore, in the present study, we have characterized the secretome of C26 colon cancer cells to identify the tumoral factors involved in cancer-induced skeletal muscle wasting. In the present study, we show that myostatin, a procachectic TGFβ (transforming growth factor β) superfamily member, is abundantly secreted by C26 cells. Consistent with myostatin signalling during cachexia, treating differentiated C2C12 myotubes with C26 CM (conditioned medium) resulted in myotubular atrophy due to the up-regulation of muscle-specific E3 ligases, atrogin-1 and MuRF1 (muscle RING-finger protein 1), and enhanced activity of the ubiquitin–proteasome pathway. Furthermore, the C26 CM also activated ActRIIB (activin receptor type II B)/Smad and NF-κB (nuclear factor κB) signalling, and reduced the activity of the IGF-I (insulin-like growth factor 1)/PI3K (phosphoinositide 3-kinase)/Akt pathway, three salient molecular features of myostatin action in skeletal muscles. Antagonists to myostatin prevented C26 CM-induced wasting in muscle cell cultures, further confirming that tumoral myostatin may be a key contributor in the pathogenesis of cancer cachexia. Finally, we show that treatment with C26 CM induced the autophagy–lysosome pathway and reduced the number of mitochondria in myotubes. These two previously unreported observations were recapitulated in skeletal muscles collected from C26 tumour-bearing mice.

scholarly journals Glycogen Synthase Kinase-3β Inhibitor Lithium Chloride Protects Against Inflammation-Mediated Skeletal Muscle Wasting

2021 ◽  
Author(s):  
Ji-Hyung Lee ◽  
Seon-Wook Kim ◽  
Jun-Hyeong Kim ◽  
Hyung-Jun Kim ◽  
JungIn Um ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Mass ◽  
Lithium Chloride ◽  
Cancer Cachexia ◽  
Muscle Wasting ◽  
Glycogen Synthase ◽  
Conditioned Media ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3Β ◽  
Skeletal Muscle Wasting

Abstract Inflammation-mediated skeletal muscle wasting is induced by inflammatory cytokines. It occurs in critically ill patients with sepsis (termed intensive care unit acquired weakness) and patients with advanced metastasis (termed cancer cachexia). Both conditions severely impact on patient morbidity and mortality. Lithium chloride has been investigated as a drug repurposing candidate for numerous diseases. In this study, we assessed whether lithium chloride affects inflammation-mediated muscle wasting, using in vitro and in vivo models of cancer cachexia and sepsis. Lithium chloride prevented wasting in myotubes cultured with cancer cell conditioned media, maintained expression of the muscle fiber contractile protein, myosin heavy chain 2 and blocked upregulation of the E3 ubiquitin ligase, Atrogin-1. Glycogen synthase kinase-3β inhibition was indicated as the target mechanism, due to the following observations: 1) β-catenin was upregulated in the myotubes and 2) inhibition of IMPA1, the secondary biological target of lithium chloride, did not inhibit the effects of cancer conditioned media. Lithium chloride inhibited upregulation of the inflammation-associated cytokines Il-1β, Il-6 and inos in macrophages treated with lipopolysaccharide. Lithium chloride treatment in an animal model of sepsis improved body weight, increased muscle mass, preserved the survival of larger fibers and decreased expression of the wasting effector genes, Atrogin-1 and Murf-1. In a model of cancer cachexia, lithium chloride increased muscle mass, enhanced muscle strength and increased fiber cross sectional area, with no significant effect on tumorigenesis. These results indicate that lithium chloride could be repurposed as a drug to treat patients with inflammation-mediated skeletal muscle wasting.

scholarly journals Inflammation Based Regulation of Cancer Cachexia

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Jill K. Onesti ◽  
Denis C. Guttridge
Keyword(s):  
Quality Of Life ◽  
Skeletal Muscle ◽  
Cancer Cachexia ◽  
Molecular Mechanisms ◽  
Muscle Wasting ◽  
Nutritional Intake ◽  
Clinical Implications ◽  
Life Outcomes ◽  
Skeletal Muscle Wasting

Cancer cachexia, consisting of significant skeletal muscle wasting independent of nutritional intake, is a major concern for patients with solid tumors that affects surgical, therapeutic, and quality of life outcomes. This review summarizes the clinical implications, background of inflammatory cytokines, and the origin and sources of procachectic factors including TNF-α, IL-6, IL-1, INF-γ, and PIF. Molecular mechanisms and pathways are described to elucidate the link between the immune response caused by the presence of the tumor and the final result of skeletal muscle wasting.

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