Muscular levels of proinflammatory cytokines correlate with a reduced expression of insulinlike growth factor-I in chronic heart failure

Schulze, P. Christian; Gielen, Stephan; Adams, Volker; Linke, Axel; Möbius‐Winkler, Sven; Erbs, Sandra; Kratzsch, Jürgen; Hambrecht, Rainer; Schuler, Gerhard

doi:10.1007/s00395-003-0411-1

Cited by 85 publications

(61 citation statements)

References 36 publications

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“…Epidemiological studies have reported a strong association between elevated expression of IL6 and IL1B genes and decreased muscle mass, strength, and crosssectional area (13,46,50). Elevated concentrations of proinflammatory cytokines may contribute to skeletal muscle atrophy by both inhibiting protein synthesis and inducing protein breakdown (19,21).…”

Section: Discussionmentioning

confidence: 99%

Maternal conjugated linoleic acid supplementation reverses high-fat diet-induced skeletal muscle atrophy and inflammation in adult male rat offspring

Pileggi

Segovia

Markworth

et al. 2016

American Journal of Physiology-Regulatory, Integrative and Comp

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-A high-saturated-fat diet (HFD) during pregnancy and lactation leads to metabolic disorders in offspring concomitant with increased adiposity and a proinflammatory phenotype in later life. During the fetal period, the impact of maternal diet on skeletal muscle development is poorly described, despite this tissue exerting a major influence on life-long metabolic health. This study investigated the effect of a maternal HFD on skeletal muscle anabolic, catabolic, and inflammatory signaling in adult rat offspring. Furthermore, the actions of maternal-supplemented conjugated linoleic acid (CLA) on these measures of muscle phenotype were investigated. A purified control diet (CD; 10% kcal fat), a CD supplemented with CLA (CLA; 10% kcal fat, 1% total fat as CLA), a high-fat (HFD; 45% kcal fat from lard), or a HFD supplemented with CLA (HFCLA; 45% kcal fat from lard, 1% total fat as CLA) was fed ad libitum to female Sprague-Dawley rats for 10 days before mating and throughout gestation and lactation. Male offspring received a standard chow diet from weaning, and the gastrocnemius was collected for analysis at day 150. Offspring from HF and HFCLA mothers displayed lower muscular protein content accompanied by elevated monocyte chemotactic protein-1, IL-6, and IL-1␤ concentrations. Phosphorylation of NF-Bp65 (Ser 536 ) and expression of the catabolic E3 ligase muscle ring finger 1 (MuRF1) were increased in HF offspring, an effect reversed by maternal CLA supplementation. The present study demonstrates the importance of early life interventions to ameliorate the negative effects of poor maternal diet on offspring skeletal muscle development. maternal obesity; nuclear factor-B

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Section: Discussionmentioning

confidence: 99%

Maternal conjugated linoleic acid supplementation reverses high-fat diet-induced skeletal muscle atrophy and inflammation in adult male rat offspring

Pileggi

Segovia

Markworth

et al. 2016

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Increases of BNP and NT-proBNP can frequently be found in diastolic dysfunction (18,19,32 ) in which the ejection fraction is normal, as well as in mild systolic dysfunction (21,22 ). In addition, modern concepts consider the heart to be a multifunctional and interactive organ that is part of a complex network (33,34 ). Several studies have shown that BNP has antifibrotic and cytoprotective properties (35,36 ).…”

Section: Discussionmentioning

confidence: 99%

Hyperhomocysteinemia and Myocardial Expression of Brain Natriuretic Peptide in Rats

et al. 2007

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Background: Hyperhomocysteinemia (HHcy) has been linked to impaired left ventricular function and clinical class in patients with chronic heart failure. We hypothesized that HHcy stimulates myocardial brain natriuretic peptide (BNP) expression and induces adverse left ventricular remodeling. Methods: We randomized 50 rats into 5 groups. Groups Co1 and Co2 (controls) received a typical diet. Groups Meth, Hcy1, and Hcy2 were fed the same diet supplemented with 2.4% methionine, 1% homocystine, and 2% homocystine, respectively. After 12 weeks, we measured total plasma homocysteine (tHcy) and BNP in plasma and tissue, and we performed histomorphometric analyses. Results: All animals had comparable baseline body weight [mean (SD) 234 (26) g] and total circulating Hcy

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“…On the basis of our criteria for severity of HF, previous work reporting plasma IL-6 levels in rats with HF appears to have been performed in rats with moderate noncongestive HF. For instance, Schulze et al (53), investigating cytokine-modulated expression of insulin-growth factor, determined that plasma IL-6 levels were not elevated in rats with HF compared with control rats. Additionally, work by Lou et al (36) also failed to show an increase in plasma IL-6 levels in rats with adriamycininduced cardiomyopathy leading to HF.…”

Section: Discussionmentioning

confidence: 99%

Increased interleukin-6 receptor expression in the paraventricular nucleus of rats with heart failure

Helwig¹,

Musch²,

Craig³

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

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Helwig BG, Musch TI, Craig RA, Kenney MJ. Increased interleukin-6 receptor expression in the paraventricular nucleus of rats with heart failure. Am J Physiol Regul Integr Comp Physiol 292: R1165-R1173, 2007. First published November 9, 2006; doi:10.1152/ajpregu.00507.2006.-Activation of the hypothalamicpituitary-adrenal (HPA) axis and augmented plasma and tissue levels of IL-6 are hallmarks of heart failure (HF). Within the forebrain, cardiovascular homeostasis is mediated in part by the paraventricular nucleus (PVN) of the hypothalamus. IL-6, via binding to the IL-6 receptor (IL-6R)/glycoprotein 130 (gp130) complex influences cellular and physiological responses. Thus, in the current study, we hypothesized that PVN IL-6R protein and gene expression are upregulated in HF vs. sham-operated rats, whereas gp130 levels in the same tissues remain stable. Six weeks after coronary ligation surgery, hemodynamic measurements were obtained, and HF rats were divided into moderate noncongestive and severe chronic congestive groups based on cardiac indices. Plasma IL-6 levels were determined and changes in gene and protein expression of IL-6R and gp130 between sham-operated and HF rats were determined via real-time PCR and Western blot analyses, respectively. Plasma levels of IL-6 were elevated in rats with severe, but not moderate, HF compared with sham-operated controls. In both moderate and severe HF rats, protein but not gene expression of IL-6R was significantly increased in PVN tissue but not in non-PVN tissue, compared with sham-operated controls. Gene and protein levels of the gp130 subunit were not altered by HF in either tissue analyzed. Collectively, these data suggest that within the brain of HF rats, IL-6R expression is not a global change. Rather the increased IL-6 levels characteristic of HF may alter PVN-mediated physiological responses via enhanced expression of the IL-6R. signal transduction; gp130; hypothalamic-pituitary axis THE PARAVENTRICULAR NUCLEUS (PVN) of the hypothalamus is a forebrain nucleus with projections to brainstem and spinal cord regions regulating cardiovascular homeostasis (10). The PVN is also a key component of the hypothalamic-pituitary-adrenal (HPA) axis. Using cytokines as messengers, bidirectional communication between the nervous and immune systems occurs along the HPA axis (16,17,39,41,54,59). Among the cytokines, IL-6 plays a significant role in HPA activation by stimulating the release of negative feedback hormones, which inhibit cytokine gene expression, resulting in attenuation of immune responses and accompanying inflammation (38,44,51).The initial step in IL-6-mediated responses is interaction of the cytokine with the interleukin-6 receptor (IL-6R), the nonsignaling subunit of the receptor complex. Binding of ligand to the alpha subunit (e.g., IL-6R) results in homodimerization of the signal transducing ␤-subunit, glycoprotein130 (gp130), at the plasma membrane (25,43,55). This recruitment allows the binding of IL-6/IL-6R to gp130, resulting in a functional receptor compl...

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Muscular levels of proinflammatory cytokines correlate with a reduced expression of insulinlike growth factor-I in chronic heart failure

Abstract: In CHF, the local IGF-I expression is reduced in the presence of normal serum levels of IGF-I. Both elevated proinflammatory cytokines and reduced local IGF-I expression contribute to a catabolic metabolism that may finally result in skeletal muscle atrophy and cardiac cachexia.

Cited by 85 publications

References 36 publications

Maternal conjugated linoleic acid supplementation reverses high-fat diet-induced skeletal muscle atrophy and inflammation in adult male rat offspring

Maternal conjugated linoleic acid supplementation reverses high-fat diet-induced skeletal muscle atrophy and inflammation in adult male rat offspring

Hyperhomocysteinemia and Myocardial Expression of Brain Natriuretic Peptide in Rats

Increased interleukin-6 receptor expression in the paraventricular nucleus of rats with heart failure

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