Marcel Orpi - Academia.edu (original) (raw)

Papers by Marcel Orpi

e-SPEN, Apr 1, 2009

Background & aims: Intra-abdominal fat is pathogenically involved in both type 2 diabetes and inf... more Background & aims: Intra-abdominal fat is pathogenically involved in both type 2 diabetes and inflammatory bowel disease (IBD). However, little is known about the interrelationships between these two widespread and devastating diseases. The goal of this study is to investigate the effect of obesity in the severity of colitis and, in turn, examine the impact of IBD on glucose tolerance during obesity. In this context, we have explored the role of infiltrating macrophages in the severity of diabetes and IBD. Methods: The infiltration of macrophages and T cells into intra-abdominal WAT, liver and the colonic lamina propria was examined in db/db and lean mice after a 7-day dextran sodium sulfate (DSS) challenge by tissue fractionation and flow cytometry. Disease activity indices (DAI), weight loss and colonic histology were examined during the course of the DSS challenge, and colonic pro-inflammatory cytokine expression was quantified by real-time RT-PCR. To determine the impact of obesity and intestinal inflammation on glucose tolerance, mice were administered an intraperitoneal glucose tolerance test. Results: We found that obesity increases the severity of experimental IBD. Following a DSS challenge, obese mice express greater concentrations of colonic TNF-a mRNA than lean mice. In addition, experimental IBD in combination with obesity worsens glucose tolerance beyond the effect caused by obesity alone. F4/80 hi CCR2 hi macrophages infiltrate the lamina propria of mice with DSS colitis and the WAT of obese mice. Conclusions: Infiltration of F4/80 hi CCR2 hi macrophages into intra-abdominal fat worsens the severity of experimental IBD during obesity. In turn, experimental IBD in obese mice repressed skeletal muscle PPAR g and GLUT4 mRNA expression, upregulated MCP-1 and worsened type 2 diabetes.

Drug Discovery Today, Jul 1, 2012

The presence of sufficient skeletal muscle mass is of paramount importance for body function and ... more The presence of sufficient skeletal muscle mass is of paramount importance for body function and the myostatin cascade is known to inhibit muscle growth in mammals. In addition, myostatin seems to have an important role in the cross-talk between skeletal muscle and adipose tissue and is involved in insulin sensitivity. In this article we highlight the latest developments related to the myostatin system, emphasizing therapeutic implications for wasting diseases and also the involvement of the system in other organs, in addition to skeletal muscle, such as heart or adipose tissue. Moreover, we highlight the possible role of the myostatin system in the cross-talk between skeletal muscle and adipose tissue, an important aspect that deserves consideration in wasting diseases.

Clinical Nutrition, Oct 1, 2008

Background & aims: Catalpic acid (CAT) is a conjugated linolenic acid (CLN) isomer containing tra... more Background & aims: Catalpic acid (CAT) is a conjugated linolenic acid (CLN) isomer containing trans-9, trans-11, cis-13 double bonds in an 18-carbon chain and it is found primarily in the seed oil of ornamental and medicinal trees and shrubs of the family Bignoniaceae. The objective of this study was to investigate whether CAT decreases obesity and ameliorates insulin sensitivity and glucose tolerance in mice fed high-fat diets. Methods: To test the efficacy of CAT in decreasing obesity and diabetes we used both a model of diet-induced obesity (DIO) and a genetic model of obesity (i.e., mice lacking the leptin receptor). Blood was collected on days 0, 7, 14, 21 and 28 for determining fasting glucose and insulin concentrations in plasma. In addition, a glucose tolerance test was administered on day 28. Results: We found that dietary CAT (1 g/100 g) decreased fasting plasma glucose and insulin concentrations, ameliorated the glucose normalizing ability following glucose challenge and decreased abdominal white adipose tissue accumulation. In white adipose tissue (WAT), CAT upregulated peroxisome proliferator-activated receptor (PPAR) a and its responsive genes [i.e., stearoyl-coenzyme A desaturase (SCD1) and enoyl-coenzyme A hydratase (ECH)], increased concentrations of high-density lipoprotein (HDL) cholesterol and decreased plasma triglyceride (TG) levels.

Journal of Cachexia, Sarcopenia and Muscle, Nov 8, 2011

Background Cachexia is a multiorganic syndrome associated with cancer, characterized by body weig... more Background Cachexia is a multiorganic syndrome associated with cancer, characterized by body weight loss, muscle and adipose tissue wasting and inflammation. Methods 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. Results 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. Conclusions These results suggest that blocking myostatin pathway could be a promising therapeutic strategy for the treatment of cancer cachexia.

Punicic acid (PUA) is a conjugated linolenic acid isomer that has shown promise in suppressing gu... more Punicic acid (PUA) is a conjugated linolenic acid isomer that has shown promise in suppressing gut inflammation. The goal of this study is to elucidate the mechanisms by which PUA modulates mucosal immunity and prevents or ameliorates gut inflammation. The expression of peroxisome proliferator-activated receptor (PPAR) α, γ and δ and their responsive genes was examined in the colonic mucosa of two mouse models of experimental inflammatory bowel disease (IBD). Immune cell-specific PPAR γ null, PPAR δ null and wild-type (WT) mice were administered control or PUA-supplemented diets and challenged with 2.5% DSS. The phenotype of immune cell subsets was examined in the mucosal and peripheral immune system. The prophylactic efficacy of PUA was also examined in an IL-10−/− model of IBD. PUA intake upregulated colonic PPAR δ, keratinocyte growth factor and the orphan nuclear receptor RORγt expression and suppressed colonic and M1 macrophage-derived TNF-α. In the mesenteric lymph nodes (i.e....

The Faseb Journal, Apr 1, 2010

Sarcopenia – Age-Related Muscle Wasting and Weakness, 2010

The aim of this chapter is to summarize and evaluate the different mechanisms and catabolic media... more The aim of this chapter is to summarize and evaluate the different mechanisms and catabolic mediators involved in cancer cachexia and ageing sarcopenia since they may represent targets for future promising clinical investigations. Cancer cachexia is a syndrome ...

Cachexia is a common systemic manifestation. Additionally, myostatin is known to be a negative re... more Cachexia is a common systemic manifestation. Additionally, myostatin is known to be a negative regulator of skeletal muscle development. The present study aimed to investigate whether formoterol down-regulates the myostatin system in skeletal muscle of tumour-bearing rats. Real-time PCR and Western blotting were used for the analysis. Results showed that rats bearing the Yoshida AH-130 ascites hepatoma, a cachexia-inducing tumour, exhibited marked muscle wasting that affected the mass of the muscles studied. The cachectic animals exhibited a significant increase in the mRNA levels of the myostatin receptor (ActIIB) in gastrocnemius muscles. Notably, the expression of the various forms of follistatin, a protein with the opposite effects to those of myostatin, was significantly reduced as a result of the implantation of the tumour. When the animals were treated with formoterol, a β-agonist with anti-cachectic potential, increases in skeletal muscle weights were observed. The β-agonist significantly increased levels of various follistatin isoforms and significantly decreased the expression levels of the myostatin receptor. In addition, formoterol treatment resulted in a significant decrease of the myostatin protein content of the gastrocnemius muscle. In conclusion, the results presented indicate that certain anabolic actions of formoterol on the skeletal muscle of cachectic animals may be mediated via the myostatin system.

Experimental and therapeutic medicine, Jul 1, 2011

Cancer cachexia occurs in the majority of cancer patients before death, and it is responsible for... more Cancer cachexia occurs in the majority of cancer patients before death, and it is responsible for the death of 22% of cancer patients. One of the most relevant characteristics of cachexia is that of asthenia, which reflects significant muscle wasting noted in cachectic cancer patients The aim of the present study was to assess whether the β(2)-adrenergic agonist formoterol is associated with an improvement in physiological parameters such as grip force and total physical activity in cachetic rats. Administration of the β(2)-agonist formoterol (0.3 mg/kg for 7 days) in rats bearing Yoshida AH-130 ascites hepatoma tumors, a model which induces a strong loss of both body and muscle weight, resulted in a significant reversal of the muscle wasting process, as reflected by individual muscle weights. The anti-wasting effects of the drug were also observed in terms of total physical activity and grip force, thus resulting in an improvement in physical performance in cachectic tumor-bearing ...

e Nutritional Immunology Group at the Virginia Bioinformatics Institute is leading three research... more e Nutritional Immunology Group at the Virginia Bioinformatics Institute is leading three research programs on nutraceutical discovery, gut health, and prevention of obesity-related infl ammation. Developing novel approaches for modulating infl ammatory responses is the central integrative theme amongst these active areas of research and discovery. Our eff ort in this reporting year comprised screening of naturally occurring compounds for

Oncology Reports, 2010

Rats bearing the Yoshida AH-130 ascites hepatoma are subjected to substantial weight loss, which ... more Rats bearing the Yoshida AH-130 ascites hepatoma are subjected to substantial weight loss, which is accompanied by anorexia at the end of the tumour cycle. Total physical activity (measured using the IR Actimeter system and Actitrack software) was determined during 11 days in control and tumour-bearing animals, skeletal muscle strength being also by the grip-strength test. The results presented clearly show that the presence of the tumour induces an earlier decrease in physical performance, which affects both skeletal muscle force and physical activity (both locomotor movements and stereotyped movements and distance travelled, among others parameters).

e-SPEN, the European e-Journal of Clinical Nutrition and Metabolism, 2009

Drug Discovery Today, 2012

Clinical Nutrition, 2010

Background & aims: Cachexia is a multiorganic syndrome associated with cancer, characterized by b... more Background & aims: Cachexia is a multiorganic syndrome associated with cancer, characterized by body weight loss, muscle and adipose tissue wasting and inflammation, being often associated with anorexia. The aim of the present investigation was to examine the effect of megestrol acetate (MA) in cachectic tumourbearing animals analyzing changes in muscle proteolysis and in parameters related with quality of life. Methods: The effects of MA (100 mg/kg) were tested in cachectic tumour-bearing rats (Yoshida AH-130 ascites hepatoma). Results: Administration of MA to tumour-bearing rats resulted in an important reversal of the muscle wasting process, as reflected by individual muscle weights. MA also decreased the rate of protein degradation in incubated isolated skeletal muscles. Real-time PCR analysis revealed that MA treatment resulted in a decrease in ubiquitin, E2 and atrogin-1 mRNA content in muscles, therefore suggesting that the main anti-proteolytic action of the drug may be based on an inhibition of the ATP-ubiquitindependent proteolytic system. The drug also improves appetite, weight loss, total physical activity and grip force. Conclusions: The results indicate that treatment with megestrol acetate increases appetite, weight loss, physical performance and muscle force in tumour-bearing rats suggesting that MA is a good candidate for muscle wasting treatment.

Clinical Nutrition, 2008

Biochimica et Biophysica Acta (BBA) - General Subjects, 2013

You may download, copy and otherwise use the AAM for non-commercial purposes provided that your l... more You may download, copy and otherwise use the AAM for non-commercial purposes provided that your license is limited by the following restrictions: (1) You may use this AAM for non-commercial purposes only under the terms of the CC-BY-NC-ND license. (2) The integrity of the work and identification of the author, copyright owner, and publisher must be preserved in any copy.

Clinical nutrition (Edinburgh, Scotland), 2012

Tumour growth is associated with weight loss resulting from both adipose and muscle wasting. Admi... more Tumour growth is associated with weight loss resulting from both adipose and muscle wasting. Administration of L-carnitine (1 g/kg body weight) to rats bearing the AH-130 Yoshida ascites hepatoma, a highly cachectic rat tumour. The treatment results in a significant improvement of food intake and in muscle weight (gastrocnemius, EDL and soleus). These beneficial effects are directly related to improved physical performance (total physical activity, mean movement velocity and total travelled distance). Administration of L-carnitine decreases proteasome activity and the expression of genes related with this activity, such as ubiquitin, C8 proteasome subunit and MuRF-1. Interestingly, L-carnitine treatment also decreases caspase-3 mRNA content therefore suggesting a modulation of apoptosis. Moreover, addition of 50 μM of L-carnitine to isolated EDL muscles results in a significant decrease in the proteolytic rate suggesting a direct effect. It can be concluded that L-carnitine suppleme...