IGF-1 and IGFBP-3 in Inflammatory Cachexia

Martín, Ana Isabel; Priego, Teresa; Moreno-Rupérez, Álvaro; González-Hedström, Daniel; Granado, Miriam; López-Calderón, Asunción

doi:10.3390/ijms22179469

Cited by 37 publications

(26 citation statements)

References 77 publications

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“…In addition to the direct effects of cytokines on muscle cells, sepsis, as well other systemic diseases, triggers modifications in the neuroendocrine system, which in turn also modulate skeletal muscle physiology [ 15 ]. Endocrine response to inflammation is characterized by a downregulation of insulin and insulin-like growth factor-1 (IGF-1), the primary anabolic signaling targeted in the skeletal muscle [ 16 , 17 , 18 ]. In addition to the down regulation of anabolic hormones, sepsis increases the secretion of glucocorticoids, which are the main catabolic hormones in skeletal muscle.…”

Section: Introductionmentioning

confidence: 99%

Role of Glucocorticoid Signaling and HDAC4 Activation in Diaphragm and Gastrocnemius Proteolytic Activity in Septic Rats

Moreno-Rupérez

Priego

González-Nicolás

et al. 2022

IJMS

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Sepsis increases glucocorticoid and decreases IGF-1, leading to skeletal muscle wasting and cachexia. Muscle atrophy mainly takes place in locomotor muscles rather than in respiratory ones. Our study aimed to elucidate the mechanism responsible for this difference in muscle proteolysis, focusing on local inflammation and IGF-1 as well as on their glucocorticoid response and HDAC4-myogenin activation. Sepsis was induced in adult male rats by lipopolysaccharide (LPS) injection (10 mg/kg), and 24 h afterwards, rats were euthanized. LPS increased TNFα and IL-10 expression in both muscles studied, the diaphragm and gastrocnemius, whereas IL-6 and SOCS3 mRNA increased only in diaphragm. In comparison with gastrocnemius, diaphragm showed a lower increase in proteolytic marker expression (atrogin-1 and LC3b) and in LC3b protein lipidation after LPS administration. LPS increased the expression of glucocorticoid induced factors, KLF15 and REDD1, and decreased that of IGF-1 in gastrocnemius but not in the diaphragm. In addition, an increase in HDAC4 and myogenin expression was induced by LPS in gastrocnemius, but not in the diaphragm. In conclusion, the lower activation of both glucocorticoid signaling and HDAC4-myogenin pathways by sepsis can be one of the causes of lower sepsis-induced proteolysis in the diaphragm compared to gastrocnemius.

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Section: Introductionmentioning

confidence: 99%

Role of Glucocorticoid Signaling and HDAC4 Activation in Diaphragm and Gastrocnemius Proteolytic Activity in Septic Rats

Moreno-Rupérez

Priego

González-Nicolás

et al. 2022

IJMS

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“…[ 28 , 29 ] Meanwhile, some inflammatory factors (Interleukin-6 and tumor necrosis factor-α) can also be used as important inflammatory parameters of sarcopenia, which can also lead to anorexia by improperly regulating muscle cell metabolism (directly or indirectly leading to increased myostatin levels, up regulating ubiquitin proteasome and renin angiotensin aldosterone systems to promote protein degradation and damage skeletal muscle regeneration) and acting as an intermediary of anorexia, which may reflect potential therapeutic targets for improving the direction of muscle metabolism and realizing certain anti-tumor mechanisms. [ 30 , 31 ]…”

Section: Discussionmentioning

confidence: 99%

The role of sarcopenia in treatment-related outcomes in patients with renal cell carcinoma: A systematic review and meta-analysis

Liu

2022

Medicine

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Background: in recent years, more attention has been paid to the fuzzy relationship between skeletal muscle components and renal cell carcinoma (RCC). This study attempts to conduct a meta-analysis using all relevant research evidence to explore the impact of sarcopenia on the final survival and recurrence outcome of RCC patients and the change process of this impact after treatment.Methods: This systematic review and Meta-analysis study took "sarcopenia", "kidney" and "tumor" and their synonyms as the main search terms, and comprehensively searched all relevant literatures published in PubMed, web of science, SpringerLink, EMBASE, Cochrane Library, Ovid (Lww oup), Wiley, ScienceDirect and Scopus databases since February 2, 2022. Multivariate hazard ratio (HR) and 95% confidence interval (CI) of overall survival (OS), cancer specific survival (CSS), and progression free survival (PFS), as well as rough data of Kaplan-Meier survival curve, were combined as the main analysis results. Subgroup analyses based on cohort characteristics (treatment, ethnicity, and BMI factors) for each study were used as secondary outcomes. The combined effect was estimated by random effect model or fixed effect model, and the heterogeneity was evaluated by I 2 value. Because this study belongs to secondary literature, the medical ethics committee of the First Affiliated Hospital of Xinjiang Medical University considers that ethical review is unnecessary.Results: Eighteen retrospective studies involving 3591 patients with RCC were analyzed, of which 71.5% were men and the median age of the cohort was 61.6. The prevalence of sarcopenia was 43% (38-48%). Sarcopenia is an independent predictor of OS (HR: 1.83, 95% CI = [1.41, 2.37]), and this prognostic value can also be reflected in Asian populations (HR: 2.59, 95% CI = [1.90, 3.54]) and drug treated patients (HR: 2.07, 95% CI = [1.07, 4.04]). Sarcopenia can also be used as an independent predictor of CSS (HR: 1.78, 95% CI = [1.34, 2.36]) and PFS (HR: 1.98, 95% CI = [1.34, 2.92]). The effect of low skeletal muscle mass on OS and CSS increased slowly from 1 to 5 years. Conclusion:Sarcopenia can be used as a comprehensive prognostic factor in RCC population, but the detailed effects from ethnic characteristics and treatment mechanism need to be further studied.Abbreviations: BIA = bioelectrical impedance analysis, BMI = body mass index, CI = confidence interval, CM = clinical modification, CSS = cancer specific survival, CT = computed tomography, DEXA = dual energy X-ray absorptiometry, HR = hazard ratio, ICD = international classification of diseases, MR = magnetic resonance, NLR = neutrophil-to-lymphocyte ratio, NOS = the Newcastle Ottawa Scale, OS = overall survival, PFS = progression free survival, RCC = renal cell carcinoma, SMI = skeletal muscle index, SO = sarcopenia obesity, VATI = visual advertisement tissue index, VFA/SFA = visual fat area/subcutaneous fat area, WHO = world health organization.

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“…In addition, although the nutraceutical was not able to prevent the decrease in IGF-1 mRNA, it prevented the LPS-induced increased in IGFBP-3 expression. The fact that IGFB-3 has been reported to increase muscle proteolysis and myoblast proliferation and differentiation ( 81 ) suggests that the nutraceutical effect decreasing IGFBP-3 levels in the gastrocnemius contributes to preserve skeletal muscle mass.…”

Section: Discussionmentioning

confidence: 99%

A Nutraceutical Product Based on a Mixture of Algae and Extra Virgin Olive Oils and Olive Leaf Extract Attenuates Sepsis-Induced Cardiovascular and Muscle Alterations in Rats

et al. 2022

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Nutraceuticals are products of natural origin widely used for the treatment and/or prevention of some chronic diseases that are highly prevalent in Western countries, such as obesity or type II diabetes, among others. However, its possible use in the prevention of acute diseases that can put life at risk has been poorly studied. Sepsis is an acute condition that causes cardiovascular and skeletal muscle damage due to a systemic inflammatory state. The aim of this work was to evaluate the possible beneficial effect of a new nutraceutical based on a mixture of algae oil (AO) and extra virgin olive oil (EVOO) supplemented with an olive leaf extract (OLE) in the prevention of cardiovascular alterations and skeletal muscle disorders induced by sepsis in rats. For this purpose, male Wistar rats were treated with the nutraceutical or with water p.o. for 3 weeks and after the treatment they were injected with 1mg/kg LPS twice (12 and 4 h before sacrifice). Pretreatment with the nutraceutical prevented the LPS-induced decrease in cardiac contractility before and after the hearts were subjected to ischemia-reperfusion. At the vascular level, supplementation with the nutraceutical did not prevent hypotension in septic animals, but it attenuated endothelial dysfunction and the increased response of aortic rings to the vasoconstrictors norepinephrine and angiotensin-II induced by LPS. The beneficial effects on cardiovascular function were associated with an increased expression of the antioxidant enzymes SOD-1 and GSR in cardiac tissue and SOD-1 and Alox-5 in arterial tissue. In skeletal muscle, nutraceutical pretreatment prevented LPS-induced muscle proteolysis and autophagy and significantly increased protein synthesis as demonstrated by decreased expression of MURF-1, atrogin-1, LC3b and increased MCH-I and MCH -IIa in gastrocnemius muscle. These effects were associated with a decrease in the expression of TNFα, HDAC4 and myogenin. In conclusion, treatment with a new nutraceutical based on a mixture of AO and EVOO supplemented with OLE is useful to prevent cardiovascular and muscular changes induced by sepsis in rats. Thus, supplementation with this nutraceutical may constitute an interesting strategy to reduce the severity and mortality risk in septic patients.

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IGF-1 and IGFBP-3 in Inflammatory Cachexia

Cited by 37 publications

References 77 publications

Role of Glucocorticoid Signaling and HDAC4 Activation in Diaphragm and Gastrocnemius Proteolytic Activity in Septic Rats

Role of Glucocorticoid Signaling and HDAC4 Activation in Diaphragm and Gastrocnemius Proteolytic Activity in Septic Rats

The role of sarcopenia in treatment-related outcomes in patients with renal cell carcinoma: A systematic review and meta-analysis

A Nutraceutical Product Based on a Mixture of Algae and Extra Virgin Olive Oils and Olive Leaf Extract Attenuates Sepsis-Induced Cardiovascular and Muscle Alterations in Rats

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