Journal: Journal of Cachexia, Sarcopenia and Muscle

Abbreviation

J Cachexia Sarcopenia Muscle

Publisher

Wiley

Journal Volumes

ISSN

2190-5991
2190-6009

Description

Filters

2017 - 20205
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Publications 1 - 5 of 5
  • Premorbid obesity, but not nutrition, prevents critical illness-induced muscle wasting and weakness
    Item type: Journal Article
    Goossens, Chloë; Bastos Marques, Mirna; Derde, Sarah; et al. (2017)
    Journal of Cachexia, Sarcopenia and Muscle
    Background The ‘obesity paradox’ of critical illness refers to better survival with a higher body mass index. We hypothesized that fat mobilized from excess adipose tissue during critical illness provides energy more efficiently than exogenous macronutrients and could prevent lean tissue wasting. Methods In lean and premorbidly obese mice, the effect of 5 days of sepsis-induced critical illness on body weight and composition, muscle wasting, and weakness was assessed, each with fasting and parenteral feeding. Also, in lean and overweight/obese prolonged critically ill patients, markers of muscle wasting and weakness were compared. Results In mice, sepsis reduced body weight similarly in the lean and obese, but in the obese with more fat loss and less loss of muscle mass, better preservation of myofibre size and muscle force, and less loss of ectopic lipids, irrespective of administered feeding. These differences between lean and obese septic mice coincided with signs of more effective hepatic fatty acid and glycerol metabolism, and ketogenesis in the obese. Also in humans, better preservation of myofibre size and muscle strength was observed in overweight/obese compared with lean prolonged critically ill patients. Conclusions During critical illness premorbid obesity, but not nutrition, optimized utilization of stored lipids and attenuated muscle wasting and weakness.
  • Hallmarks of Frailty and Osteosarcopenia in Prematurely Aged PolgA (D257A/D257A) Mice
    Item type: Journal Article
    Scheuren, Ariane; D'Hulst, Gommaar; Kuhn, Gisela; et al. (2020)
    Journal of Cachexia, Sarcopenia and Muscle
    Background Frailty is a geriatric syndrome characterized by increased susceptibility to adverse health outcomes. One major determinant thereof is the gradual weakening of the musculoskeletal system and the associated osteosarcopenia. To improve our understanding of the underlying pathophysiology and, more importantly, to test potential interventions aimed at counteracting frailty, suitable animal models are needed. Methods To evaluate the relevance of prematurely aged PolgA(D257A/D257A) mice as a model for frailty and osteosarcopenia, we quantified the clinical mouse frailty index in PolgA(D257A/D257A) and wild‐type littermates (PolgA(+/+), WT) with age and concertedly assessed the quantity and quality of bone and muscle tissue. Lastly, the anabolic responsiveness of skeletal muscle, muscle progenitors, and bone was assessed. Results PolgA(D257A/D257A) accumulated health deficits at a higher rate compared with WT, resulting in a higher frailty index at 40 and 46 weeks of age (+166%, +278%, P < 0.0001), respectively, with no differences between genotypes at 34 weeks. Concomitantly, PolgA(D257A/D257A) displayed progressive musculoskeletal deterioration such as reduced bone and muscle mass as well as impaired functionality thereof. In addition to lower muscle weights (−14%, P < 0.05, −23%, P < 0.0001) and fibre area (−20%, P < 0.05, −22%, P < 0.0001) at 40 and 46 weeks, respectively, PolgA(D257A/D257A) showed impairments in grip strength and concentric muscle forces (P < 0.05). PolgA(D257A/D257A) mutation altered the acute response to various anabolic stimuli in skeletal muscle and muscle progenitors. While PolgA(D257A/D257A) muscles were hypersensitive to eccentric contractions as well as leucine administration, shown by larger downstream signalling response of the mechanistic target of rapamycin complex 1, myogenic progenitors cultured in vitro showed severe anabolic resistance to leucine and robust impairments in cell proliferation. Longitudinal micro‐computed tomography analysis of the sixth caudal vertebrae showed that PolgA(D257A/D257A) had lower bone morphometric parameters (e.g. bone volume fraction, trabecular, and cortical thickness, P < 0.05) as well as reduced remodelling activities (e.g. bone formation and resorption rate, P < 0.05) compared with WT. When subjected to 4 weeks of cyclic loading, young but not aged PolgA(D257A/D257A) caudal vertebrae showed load‐induced bone adaptation, suggesting reduced mechanosensitivity with age. Conclusions PolgA(D257A/D257A) mutation leads to hallmarks of age‐related frailty and osteosarcopenia and provides a powerful model to better understand the relationship between frailty and the aging musculoskeletal system.
  • Comprehensive proteome analysis of human skeletal muscle in cachexia and sarcopenia: A pilot study
    Item type: Journal Article
    Ebhardt, Holger A.; Degen, Simone; Tadini, Valentina; et al. (2017)
    Journal of Cachexia, Sarcopenia and Muscle
    Background Cancer cachexia (cancer‐induced muscle wasting) is found in a subgroup of cancer patients leaving the patients with a poor prognosis for survival due to a lower tolerance of the chemotherapeutic drug. The cause of the muscle wasting in these patients is not fully understood, and no predictive biomarker exists to identify these patients early on. Skeletal muscle loss is an inevitable consequence of advancing age. As cancer frequently occurs in old age, identifying and differentiating the molecular mechanisms mediating muscle wasting in cancer cachexia vs. age‐related sarcopenia are a challenge. However, the ability to distinguish between them is critical for early intervention, and simple measures of body weight may not be sufficiently sensitive to detect cachexia early. Methods We used a range of omics approaches: (i) undepleted proteome was quantified using advanced high mass accuracy mass spectrometers in SWATH‐MS acquisition mode; (ii) phospho epitopes were quantified using protein arrays; and (iii) morphology was assessed using fluorescent microscopy. Results We quantified the soluble proteome of muscle biopsies from cancer cachexia patients and compared them with cohorts of cancer patients and healthy individuals with and without age‐related muscle loss (aka age‐related sarcopenia). Comparing the proteomes of these cohorts, we quantified changes in muscle contractile myosins and energy metabolism allowing for a clear identification of cachexia patients. In an in vitro time lapse experiment, we mimicked cancer cachexia and identified signal transduction pathways governing cell fusion to play a pivotal role in preventing muscle regeneration. Conclusions The work presented here lays the foundation for further understanding of muscle wasting diseases and holds the promise of overcoming ambiguous weight loss as a measure for defining cachexia to be replaced by a precise protein signature.
  • Uncoupling protein 1 expression in adipocytes derived from skeletal muscle fibro/adipogenic progenitors is under genetic and hormonal control
    Item type: Journal Article
    Gorski, Tatiane; Mathes, Sebastian; Krützfeldt, Jan (2018)
    Journal of Cachexia, Sarcopenia and Muscle
  • Anorexia-cachexia syndrome in hepatoma tumour-bearing rats requires the area postrema but not vagal afferents and is paralleled by increased MIC-1/GDF15
    Item type: Journal Article
    Borner, Tito; Arnold, Myrtha; Ruud, Johan; et al. (2017)
    Journal of Cachexia, Sarcopenia and Muscle
    Background The cancer-anorexia-cachexia syndrome (CACS) negatively affects survival and therapy success in cancer patients. Inflammatory mediators and tumour-derived factors are thought to play an important role in the aetiology of CACS. However, the central and peripheral mechanisms contributing to CACS are insufficiently understood. The area postrema (AP) and the nucleus tractus solitarii are two important brainstem centres for the control of eating during acute sickness conditions. Recently, the tumour-derived macrophage inhibitory cytokine-1 (MIC-1) emerged as a possible mediator of cancer anorexia because lesions of these brainstem areas attenuated the anorectic effect of exogenous MIC-1 in mice. Methods Using a rat hepatoma tumour model, we examined the roles of the AP and of vagal afferents in the mediation of CACS. Specifically, we investigated whether a lesion of the AP (APX) or subdiaphragmatic vagal deafferentation (SDA) attenuate anorexia, body weight, muscle, and fat loss. Moreover, we analysed MIC-1 levels in this tumour model and their correlation with tumour size and the severity of the anorectic response. Results In tumour-bearing sham-operated animals mean daily food intake significantly decreased. The anorectic response was paralleled by a significant loss of body weight and muscle mass. APX rats were protected against anorexia, body weight loss, and muscle atrophy after tumour induction. In contrast, subdiaphragmatic vagal deafferentation did not attenuate cancer-induced anorexia or body weight loss. Tumour-bearing rats had substantially increased MIC-1 levels, which positively correlated with tumour size and cancer progression and negatively correlated with food intake. Conclusions These findings demonstrate the importance of the AP in the mediation of cancer-dependent anorexia and body weight loss and support a pathological role of MIC-1 as a tumour-derived factor mediating CACS, possibly via an AP-dependent action.
Publications 1 - 5 of 5