Rheumatoid cachexia: A complication of rheumatoid arthritis moves into the 21st century

Immunology R&D, Biogen Idec, Inc,, Cambridge, MA 02142, USA. .
Arthritis research & therapy (Impact Factor: 3.75). 04/2009; 11(2):108. DOI: 10.1186/ar2658
Source: PubMed


Rheumatoid cachexia, loss of muscle mass and strength and concomitant increase in fat mass, is very common in patients with rheumatoid arthritis (RA). Despite great advances in the treatment of RA, it appears that rheumatoid cachexia persists even after joint inflammation improves. Rheumatoid cachexia may be an important risk factor for cardiovascular disease and excess mortality in RA. In this issue of Arthritis Research & Therapy, Elkan and colleagues demonstrate a link between rheumatoid cachexia and metabolic syndrome, further reinforcing the need for therapy directed beyond inflammation and at the metabolic consequences of RA.

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Available from: Ronenn Roubenoff
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    • "Changes in body composition have been found in patients with RA, with reduced fat-free mass and increased fat mass and, thus, with little or no weight loss or with a maintained body mass index. This condition has been named “rheumatoid cachexia” and is believed to accelerate morbidity and mortality in RA and has also been linked to MS [35, 36]. "
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    ABSTRACT: Insulin resistance is an essential feature of the metabolic syndrome that has been linked to rheumatoid arthritis (RA). Understanding how inflammation arising in one tissue affects the physiology and pathology of other organs remains an unanswered question with therapeutic implications for chronic conditions including obesity, diabetes mellitus, atherosclerosis, and RA. Adipokines may play a role in the development of atherogenesis in patients with RA. Biologic therapies, such as TNF-α antagonists, that block proinflammatory cytokines have beneficial effects on the insulin resistance that is often observed in patients with RA.
    Full-text · Article · Jan 2013 · Mediators of Inflammation
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    • "Several dissimilarities exist between RA and experimental rodent models of this illness that can explain the different impact on circulating adipokines. One of them is that experimental arthritis dramatically decreases WAT mass, whereas rheumatoid cachexia is usually associated with increased adipose tissue mass (23). Therefore, it is not surprising that hormones released by adipose tissue are modified differently in both types of arthritis. "
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    ABSTRACT: Chronic inflammation induces skeletal muscle wasting and cachexia. In arthritic rats, fenofibrate, a peroxisome proliferator-activated receptor α (PPARα (PPARA)) agonist, reduces wasting of gastrocnemius, a predominantly glycolytic muscle, by decreasing atrogenes and myostatin. Considering that fenofibrate increases fatty acid oxidation, the aim of this study was to elucidate whether fenofibrate is able to prevent the effect of arthritis on serum adipokines and on soleus, a type I muscle in which oxidative metabolism is the dominant source of energy. Arthritis was induced by injection of Freund's adjuvant. Four days after the injection, control and arthritic rats were gavaged daily with fenofibrate (300 mg/kg bw) or vehicle over 12 days. Arthritis decreased serum leptin, adiponectin, and insulin (P<0.01) but not resistin levels. In arthritic rats, fenofibrate administration increased serum concentrations of leptin and adiponectin. Arthritis decreased soleus weight, cross-sectional area, fiber size, and its Ppar α mRNA expression. In arthritic rats, fenofibrate increased soleus weight, fiber size, and Ppar α expression and prevented the increase in Murf1 mRNA. Fenofibrate decreased myostatin, whereas it increased MyoD (Myod1) and myogenin expressions in the soleus of control and arthritic rats. These data suggest that in oxidative muscle, fenofibrate treatment is able to prevent arthritis-induced muscle wasting by decreasing Murf1 and myostatin expression and also by increasing the myogenic regulatory factors, MyoD and myogenin. Taking into account the beneficial action of adiponectin on muscle wasting and the correlation between adiponectin and soleus mass, part of the anticachectic action of fenofibrate may be mediated through stimulation of adiponectin secretion.
    Full-text · Article · Jul 2012 · Endocrine Connections
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    • "As a model for in vivo chronic inflammation, we have used muscle biopsies obtained from patients suffering from rheumatoid arthritis (RA) compared to patients with osteoarthritis (OA), without signs of chronic inflammation. Patients with RA have been shown to have a steeper decline in muscle mass and strength compared to the general population, which might be due to the chronic inflammatory state of these patients [13,14]. "
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    ABSTRACT: Chronic inflammation is a profound systemic modification of the cellular microenvironment which could affect survival, repair and maintenance of muscle stem cells. The aim of this study was to define the role of chronic inflammation on the regenerative potential of satellite cells in human muscle. As a model for chronic inflammation, 11 patients suffering from rheumatoid arthritis (RA) were included together with 16 patients with osteoarthritis (OA) as controls. The mean age of both groups was 64 years, with more females in the RA group compared to the OA group. During elective knee replacement surgery, a muscle biopsy was taken from the distal musculus vastus medialis. Cell populations from four RA and eight OA patients were used for extensive phenotyping because these cell populations showed no spontaneous differentiation and myogenic purity greater than 75% after explantation. After mononuclear cell explantation, myogenic purity, viability, proliferation index, number of colonies, myogenic colonies, growth speed, maximum number of population doublings and fusion index were not different between RA and OA patients. Furthermore, the expression of proteins involved in replicative and stress-induced premature senescence and apoptosis, including p16, p21, p53, hTERT and cleaved caspase-3, was not different between RA and OA patients. Mean telomere length was shorter in the RA group compared to the OA group. In the present study we found evidence that chronic inflammation in RA does not affect the in vitro regenerative potential of human satellite cells. Identification of mechanisms influencing muscle regeneration by modulation of its microenvironment may, therefore, be more appropriate.
    Full-text · Article · Dec 2011 · Arthritis research & therapy
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