Volume 3 (2012)
Page 1 - 4
Mitja Lainscak, Stephan von Haehling, Wolfram Doehner and Stefan D. Anker
The obesity paradox in chronic disease: facts and numbersBody size, particularly large, is a matter of concern among the lay public. Whether this is justified depends upon the state of health and should be judged individually. For patients with established chronic disease, there is sufficient evidence to support the benefits of large body size, i.e., the obesity paradox. This uniform finding is shared over a variety of cardiovascular, pulmonary, and renal diseases and is counterintuitive to the current concepts on ideal body weight. The scientific community has to increase the awareness about differences for optimal body size in health and disease. Simultaneously, clinicians have to be aware about body weight dynamics implications and should interpret the changes in the context of an underlying disease in order to implement the best available management.
Lainscak M., von Haehling S., Doehner W. and Anker S.D. The obesity paradox in chronic disease: facts and numbers. J Cachex Sarcopenia Muscle 2012;1:1-4.
Page 5 - 11
Mary A. Honors and Kimberly P. Kinzig
The role of insulin resistance in the development of muscle wasting during cancer cachexiaBackground
Cancer cachexia is a complex syndrome associated with multiple metabolic abnormalities. Insulin resistance is present in many cancer patients and may be one mechanism through which muscle wasting occurs.
Methods and results
The present review examines evidence in support of a role for insulin resistance in the development of muscle wasting during cancer cachexia and identifies areas for future research. Patients suffering from cancer cachexia tend to exhibit insulin resistance and improvements in insulin resistance have the potential to improve cachexia symptoms. In addition, evidence suggests that insulin resistance may occur prior to the onset of cachexia symptoms.
Further investigation of the role of insulin resistance in cancer cachexia is needed. The use of translational research in this area is strongly encouraged, and has important implications for clinical research and the treatment and prevention of cancer cachexia.
Honors M.A., Kinzig K.P. The role of insulin resistance in the development of muscle wasting during cancer cachexia J Cachex Sarcopenia Muscle 2012;1:5-11.
Page 13 - 23
Elisabetta Ferraro, Francesca Molinari and Libera Berghella
Molecular control of neuromuscular junction developmentSkeletal muscle innervation is a multi-step process leading to the neuromuscular junction (NMJ) apparatus formation. The transmission of the signal from nerve to muscle occurs at the NMJ level. The molecular mechanism that orchestrates the organization and functioning of synapses is highly complex, and it has not been completely elucidated so far. Neuromuscular junctions are assembled on the muscle fibers at very precise locations called end plates (EP). Acetylcholine receptor (AChR) clusterization at the end plates is required for an accurate synaptic transmission. This review will focus on some mechanisms responsible for accomplishing the correct distribution of AChRs at the synapses. Recent evidences support the concept that a dual transcriptional control of AChR genes in subsynaptic and extrasynaptic nuclei is crucial for AChR clusterization. Moreover, new players have been discovered in the agrin–MuSK pathway, the master organizer of postsynaptical differentiation. Mutations in this pathway cause neuromuscular congenital disorders. Alterations of the postynaptic apparatus are also present in physiological conditions characterized by skeletal muscle wasting. Indeed, recent evidences demonstrate how NMJ misfunctioning has a crucial role at the onset of age-associated sarcopenia.
Ferraro E., Molinari F., Berghella L. Molecular control of neuromuscular junction development J Cachex Sarcopenia Muscle 2012;1:13-23.
Page 25 - 29
Colin E. Webber and Ronald D. Barr
Skeletal muscle mass (SMM) can be extracted from whole-body scans obtained by X-ray-based dual-photon absorptiometry (DXA). There is a need to establish expected age-dependent values for children and adolescents.
Appendicular lean tissue mass (ALM) was extracted from whole-body DXA scans in 140 healthy children and adolescents (68 females and 72 males). Whole-body SMM was calculated from ALM using equations developed by Kim et al. (Am J Clin Nutr 84:1014–1020, 2006). Age-dependent patterns of increase in SMM were derived by fitting SMM values to equations that consisted of the sum of two logistic expressions, one accounting for SMM changes during growth and the other for SMM changes during puberty. Normal ranges were defined so that 95% of the SMM values were included.
The reproducibility of SMM measurements was obtained from whole-body DXA scans repeated on three occasions in each of a separate group of 32 normal children with repositioning between scans.
Normal ranges are presented as equations describing the age-dependent pattern of increase in SMM as well as population standard deviations that increased steadily with age. For 15 children below age 10, SMM reproducibility (95% CI) was 149 g (119–199 g) while for 17 children and adolescents over age 10, reproducibility was 170 g (138–223 g).
DXA-based measurements of SMM in children and adolescents are reproducible and can be expressed in terms of age-dependent Z scores.
Webber C.E.,Barr R.D. Age- and gender-dependent values of skeletal muscle mass in healthy children and adolescents J Cachex Sarcopenia Muscle 2012;1:25-29.
Page 31 - 36
Anika Tschirner, Stephan von Haehling, Sandra Palus, Wolfram Doehner, Stefan D. Anke and Jochen Springer
Ursodeoxycholic acid treatment in a rat model of cancer cachexiaBackground
Cancer cachexia is characterized by loss of both adipose and skeletal muscle tissue and by an increased production of proinflammatory cytokines. Ursodeoxycholic acid (UDCA), a bile acid used for centuries in the treatment of liver disease, is known to confer anti-inflammatory and anti-apoptotic effects as well as beneficial effects on mitochondrial integrity and cell signaling. We hypothesized that UDCA ameliorates the wasting process in the Yoshida hepatoma tumor model. In addition, we sought to establish if UDCA exerts beneficial effects on survival in this model.
Methods and results
Forty-seven male rats were inoculated intraperitoneally with 108 Yoshida hepatoma AH-130 cells and treated with placebo or one of two different doses of UDCA, 25 or 100 mg/kg daily. Body weight, body composition, and activity indicators were measured over the course of study up to day 16. UDCA treatment had no effect on tumor growth, loss of body weight, and loss of fat mass. Compared with placebo, low-dose UDCA improved tissue loss in the lung (p = 0.022) and tended to reduce tissue loss in brown adipocytes (p = 0.06), gastrocnemius muscle (p = 0.06), extensor digitorum longus muscle (p = 0.09), and soleus muscle (p = 0.07). Compared with placebo, high-dose UDCA tended to reduce the loss of lean body mass (p = 0.06), lung tissue (p = 0.1), white adipose tissue (p = 0.11), and gastrocnemius muscle (p = 0.11). The activity and food intake were not altered in tumor-bearing rats by either dose of UDCA. Both doses tended to decrease the mortality rate in tumor-bearing rats, (hazard ratio (HR), 0.42; 95% confidence interval (CI), 0.17–1.04; p = 0.061 for low-dose UDCA; HR, 0.44; 95% CI, 0.18–1.05; p = 0.065 for high-dose UDCA).
UDCA treatment in the Yoshida hepatoma model showed a trend towards attenuation of tissue loss in animals with progressive weight loss in cancer cachexia. Tumor growth and activity indicators were not altered. Both doses of UDCA tended to reduce the mortality rates in tumor-bearing animals. Larger studies with longer follow-up are required to verify these findings.
Tschirner A., von Haehling S., Palus S., Doehner W., Anker S.D., Springer J. Ursodeoxycholic acid treatment in a rat model of cancer cachexia J Cachex Sarcopenia Muscle 2012;1:31-36.
Page 37 - 43
Sílvia Busquets, Míriam Toledo, Marcel Orpí, David Massa, Maria Porta, Eva Capdevila, Núria Padilla, Valentina Frailis, Francisco J. López-Soriano, H. Q. Han and Josep M. Argilés
Myostatin blockage using actRIIB antagonism in mice bearing the Lewis lung carcinoma results in the improvement of muscle wasting and physical performanceBackground
Cachexia is a multiorganic syndrome associated with cancer, characterized by body weight loss, muscle and adipose tissue wasting and inflammation.
The aim of this investigation was to examine the effect of the soluble receptor antagonist of myostatin (sActRIIB) in cachectic tumor-bearing animals analyzing
changes in muscle proteolysis and in quality of life.
Administration of sActRIIB resulted in an improvement in body and muscle weights.
Administration of the soluble receptor antagonist of myostatin also resulted in an improvement in the muscle force.
These results suggest that blocking myostatin pathway could be a promising therapeutic strategy for the treatment of cancer cachexia.
Busquets S., Toledo M., Orpí M., Massa D., Porta M., Capdevila E., Padilla N., Frailis V., López-Soriano F.J., Han H. Q., Argilés J.M. Ursodeoxycholic acid treatment in a rat model of cancer cachexia J Cachex Sarcopenia Muscle 2012;1:37-43.
Page 45 - 50
Nicole Ebner, Claudia G. Werner, Wolfram Doehner, Stefan D. Anker and Stephan von Haehling
Ebner N., Werner C.G., Doehner W., Anker S.D., von Haehling S. Recent developments in the treatment of cachexia: highlights from the 6th Cachexia Conference J Cachex Sarcopenia Muscle 2012;1:45-50.
Page 51 - 68
Letter to the Editor Page 69 - 70
Christopher J. Oliver
Letter to the Editor Page 71 - 70
Nima Alamdari and Per-Olof Hasselgren