Papers by Sandra Bonhomme
Les patients diabetiques de type 2 (DT2) obeses presentent un etat inflammatoire chronique lie a ... more Les patients diabetiques de type 2 (DT2) obeses presentent un etat inflammatoire chronique lie a des alterations immunitaires. L’arginine (Arg), dont la disponibilite est reduite lors du diabete, est un acide amine essentiel lors du sepsis et agit essentiellement via le monoxyde d’azote (NO). En effet, le NO joue un role majeur dans la fonctionnalite des macrophages et sa production depend de la disponibilite en Arg et de l’activite enzymatique de la NO synthase inductible (iNOS) et de l’arginase. Dans une premiere etude, notre hypothese est que la dysimmunite associee au DT2 pourrait etre la consequence d’alterations du metabolisme de l’Arg. Notre but est de caracteriser in vitro le metabolisme de l’Arg dans des macrophages peritoneaux de rats DT2. Nous avons utilise des macrophages issus de rats Zucker Diabetic Fatty (ZDF) fa/fa, DT2 et de rats temoins +/fa. Nous montrons la normalisation de la production de NO dans les macrophages de rats DT2 par l’Arg, et le role potentiellement majeur de l’arginase II dans la production de NO. L’hypothese de la seconde etude est qu’un apport en Arg ameliore le metabolisme et l’immunite dans un modele de rat DT2 et endotoxemique. Notre but est d’evaluer in vivo les effets d’une nutrition enterale enrichie en Arg chez des rats fa/fa. On montre d’abord que la charge en azote, plutot que l’Arg per se, serait une cause de mortalite. De plus, on montre l’amelioration du bilan azote et du metabolisme des triglycerides par l’Arg. On montre l’effet anti-inflammatoire de l’Arg et qu’elle regule la production de NO par le controle de l’expression proteique de l’arginase I. Cette derniere etude confirme les effets benefiques de l’Arg.
The FASEB Journal, Mar 1, 2006
Methods: Macrophages from male Zucker Diabetic Fatty (ZDF) rats (fa/fa) or lean ZDF rats (+/fa) w... more Methods: Macrophages from male Zucker Diabetic Fatty (ZDF) rats (fa/fa) or lean ZDF rats (+/fa) were incubated without or with lipopolysaccharide (LPS; E. coli: 0127:B8 at 10μg/ml) for 3 h for the ...
Nutrition, 2013
Objective: Critically ill diabetic and obese patients are at high risk of complications. Arginine... more Objective: Critically ill diabetic and obese patients are at high risk of complications. Arginine availability is lowered in diabetes and in stress situations, yet arginine is necessary for immune response, mainly by its action through nitric oxide (NO). These facts argue for arginine-supplemented diets in critically ill patients. However, studies have raised concerns about possible adverse effects of such diets in intensive-care patients. We therefore analyzed the metabolic and immunologic effects of an arginine-enriched diet in stressed diabetic-obese rats. Methods: Zucker Diabetic Fatty rats (fa/fa) were made endotoxemic by an intraperitoneal injection of lipopolysaccharide and then fed 4-d enteral nutrition enriched with arginine (ARG group) or a nonessential amino acid mix (NEAA group). The two groups each were subdivided into three subgroups: the ARG subgroups received 0.5 g (ARG0.5), 2 g (ARG2), and 5 g (ARG5) of arginine per kilogram daily, and the NEAA groups were made isonitrogenous with the corresponding ARG subgroups (NEAA0.5, NEAA2, and NEAA5). Plasma and urinary biomarkers were measured. Cytokine and NO production levels and inducible NO synthase and arginase protein levels were determined from peritoneal macrophages. Results: The survival rate was lower in the ARG5 and NEAA5 subgroups than in all the other subgroups. The nitrogen balance was higher in the ARG5 group than in the NEAA5 group. Plasma triacylglycerol levels were lower in the ARG2 group than in the NEAA2 group. Interleukin-6, tumor necrosis factor-a, and NO production in the macrophages decreased and arginase-1 was upregulated in the ARG-treated rats. Conclusions: In this model, mortality was increased by the nitrogen burden rather than by arginine per se. Arginine improved nitrogen balance and had an anti-inflammatory action on macrophages by regulating NO production, probably through arginase-1 expression.
Clinical Nutrition, Jun 1, 2012
Background & aims: Excess weight and type 2 diabetes lead to increased susceptibility to infectio... more Background & aims: Excess weight and type 2 diabetes lead to increased susceptibility to infections. Our aim was to investigate the role of diabetes-induced decreased arginine (Arg) availability and of a possible dysregulation of Arg metabolism in macrophages favoring inflammation and dysimmunity via altered nitric oxide (NO) and cytokine productions. Methods: Isolated peritoneal macrophages from Zucker Diabetic Fatty (ZDF) or lean rats were incubated with increasing Arg concentration (0e2 mM) and Arg metabolism and regulatory properties were studied. Results: Inducible NO synthase (iNOS) expression did not vary with Arg concentration while NO production reached a maximum at 0.5 mM Arg, being significantly lower in macrophages from ZDF rats. Arginase I and II protein levels reached a maximum between 0.25 and 0.5 mM Arg in controls; in macrophages from ZDF rats arginase I was significantly lower and progressively increased up to 2 mM Arg while arginase II was not affected by Arg concentration. In parallel, Arg downregulated TNFa production in both groups and IL-6 only in control. Conclusions: This in vitro study shows that Arg metabolism is impaired in macrophages from diabeticobese rats and that improving Arg availability for these cells restores NO production and contributes to the regulation of the inflammatory process.
British Journal of Nutrition, Nov 13, 2014
In type 2 diabetes (T2D) macrophage dysfunction increases susceptibility to infection and mortali... more In type 2 diabetes (T2D) macrophage dysfunction increases susceptibility to infection and mortality. This may result from the associated decreased plasma concentration of arginine, an amino acid that plays an important role in immunity. In vitro, increasing arginine availability leads to an improvement in macrophage function; however, arginine supplementation in diabetic obese patients may be detrimental. The aim of the present study was to assess in vitro whether citrulline, an arginine precursor, could replace arginine in the regulation of macrophage function under a condition of diabetes and obesity. Peritoneal macrophages from diabetic obese or lean rats were incubated for 6 h in an arginine-free medium, in the presence of increasing citrulline concentrations (0•1, 0•5, 1 or 2 mmol/l). Cytokine and NO production was determined. Peritoneal macrophages from either lean or diabetic obese rats produced NO, and at higher levels in the cells from lean rats. In diabetic obese rats, TNF-a production decreased with increasing citrulline concentrations, but was higher than that in the cells from lean rats. In contrast, IL-6 production increased with increasing citrulline concentrations. The present experiment shows that citrulline is effectively used for NO production and regulates cytokine production in macrophages from diabetic obese rats. This effect warrants in vivo evaluation in T2D-related inflammation.
Clinical Nutrition, 2012
Background & aims: Excess weight and type 2 diabetes lead to increased susceptibility to infectio... more Background & aims: Excess weight and type 2 diabetes lead to increased susceptibility to infections. Our aim was to investigate the role of diabetes-induced decreased arginine (Arg) availability and of a possible dysregulation of Arg metabolism in macrophages favoring inflammation and dysimmunity via altered nitric oxide (NO) and cytokine productions. Methods: Isolated peritoneal macrophages from Zucker Diabetic Fatty (ZDF) or lean rats were incubated with increasing Arg concentration (0e2 mM) and Arg metabolism and regulatory properties were studied. Results: Inducible NO synthase (iNOS) expression did not vary with Arg concentration while NO production reached a maximum at 0.5 mM Arg, being significantly lower in macrophages from ZDF rats. Arginase I and II protein levels reached a maximum between 0.25 and 0.5 mM Arg in controls; in macrophages from ZDF rats arginase I was significantly lower and progressively increased up to 2 mM Arg while arginase II was not affected by Arg concentration. In parallel, Arg downregulated TNFa production in both groups and IL-6 only in control. Conclusions: This in vitro study shows that Arg metabolism is impaired in macrophages from diabeticobese rats and that improving Arg availability for these cells restores NO production and contributes to the regulation of the inflammatory process.
The FASEB Journal, 2006
Methods: Macrophages from male Zucker Diabetic Fatty (ZDF) rats (fa/fa) or lean ZDF rats (+/fa) w... more Methods: Macrophages from male Zucker Diabetic Fatty (ZDF) rats (fa/fa) or lean ZDF rats (+/fa) were incubated without or with lipopolysaccharide (LPS; E. coli: 0127:B8 at 10μg/ml) for 3 h for the ...
Nutrition, 2013
Objective: Critically ill diabetic and obese patients are at high risk of complications. Arginine... more Objective: Critically ill diabetic and obese patients are at high risk of complications. Arginine availability is lowered in diabetes and in stress situations, yet arginine is necessary for immune response, mainly by its action through nitric oxide (NO). These facts argue for arginine-supplemented diets in critically ill patients. However, studies have raised concerns about possible adverse effects of such diets in intensive-care patients. We therefore analyzed the metabolic and immunologic effects of an arginine-enriched diet in stressed diabetic-obese rats. Methods: Zucker Diabetic Fatty rats (fa/fa) were made endotoxemic by an intraperitoneal injection of lipopolysaccharide and then fed 4-d enteral nutrition enriched with arginine (ARG group) or a nonessential amino acid mix (NEAA group). The two groups each were subdivided into three subgroups: the ARG subgroups received 0.5 g (ARG0.5), 2 g (ARG2), and 5 g (ARG5) of arginine per kilogram daily, and the NEAA groups were made isonitrogenous with the corresponding ARG subgroups (NEAA0.5, NEAA2, and NEAA5). Plasma and urinary biomarkers were measured. Cytokine and NO production levels and inducible NO synthase and arginase protein levels were determined from peritoneal macrophages. Results: The survival rate was lower in the ARG5 and NEAA5 subgroups than in all the other subgroups. The nitrogen balance was higher in the ARG5 group than in the NEAA5 group. Plasma triacylglycerol levels were lower in the ARG2 group than in the NEAA2 group. Interleukin-6, tumor necrosis factor-a, and NO production in the macrophages decreased and arginase-1 was upregulated in the ARG-treated rats. Conclusions: In this model, mortality was increased by the nitrogen burden rather than by arginine per se. Arginine improved nitrogen balance and had an anti-inflammatory action on macrophages by regulating NO production, probably through arginase-1 expression.
The Faseb Journal, Mar 1, 2006
Methods: Macrophages from male Zucker Diabetic Fatty (ZDF) rats (fa/fa) or lean ZDF rats (+/fa) w... more Methods: Macrophages from male Zucker Diabetic Fatty (ZDF) rats (fa/fa) or lean ZDF rats (+/fa) were incubated without or with lipopolysaccharide (LPS; E. coli: 0127:B8 at 10μg/ml) for 3 h for the ...
Les patients diabetiques de type 2 (DT2) obeses presentent un etat inflammatoire chronique lie a ... more Les patients diabetiques de type 2 (DT2) obeses presentent un etat inflammatoire chronique lie a des alterations immunitaires. L’arginine (Arg), dont la disponibilite est reduite lors du diabete, est un acide amine essentiel lors du sepsis et agit essentiellement via le monoxyde d’azote (NO). En effet, le NO joue un role majeur dans la fonctionnalite des macrophages et sa production depend de la disponibilite en Arg et de l’activite enzymatique de la NO synthase inductible (iNOS) et de l’arginase. Dans une premiere etude, notre hypothese est que la dysimmunite associee au DT2 pourrait etre la consequence d’alterations du metabolisme de l’Arg. Notre but est de caracteriser in vitro le metabolisme de l’Arg dans des macrophages peritoneaux de rats DT2. Nous avons utilise des macrophages issus de rats Zucker Diabetic Fatty (ZDF) fa/fa, DT2 et de rats temoins +/fa. Nous montrons la normalisation de la production de NO dans les macrophages de rats DT2 par l’Arg, et le role potentiellement...
The Faseb Journal, Mar 1, 2006
British Journal of Nutrition, 2014
In type 2 diabetes (T2D) macrophage dysfunction increases susceptibility to infection and mortali... more In type 2 diabetes (T2D) macrophage dysfunction increases susceptibility to infection and mortality. This may result from the associated decreased plasma concentration of arginine, an amino acid that plays an important role in immunity.In vitro, increasing arginine availability leads to an improvement in macrophage function; however, arginine supplementation in diabetic obese patients may be detrimental. The aim of the present study was to assessin vitrowhether citrulline, an arginine precursor, could replace arginine in the regulation of macrophage function under a condition of diabetes and obesity. Peritoneal macrophages from diabetic obese or lean rats were incubated for 6 h in an arginine-free medium, in the presence of increasing citrulline concentrations (0·1, 0·5, 1 or 2 mmol/l). Cytokine and NO production was determined. Peritoneal macrophages from either lean or diabetic obese rats produced NO, and at higher levels in the cells from lean rats. In diabetic obese rats, TNF-α ...
Clinical Nutrition Supplements, 2008
Alzheimer's & Dementia, 2013
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Papers by Sandra Bonhomme