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10. Effects of protein malnutrition on IL-6-mediated signaling in the liver and the systemic acute-phase response in rats

Author

Ling, Pei-Ra, Smith, Robert J., Kie, Susanne, Boyce, Patricia, and Bistrian, Bruce R.

Subjects
Liver -- Research, Proteins -- Research, Biological sciences
Abstract

Effects of protein malnutrition on IL-6mediated signaling in the liver and the systemic acute-phase response in rats. Am J Physiol Regul Integr Comp Physiol 287: R801-R808, 2004: 10.1152/ajpregu.00715.2003.--This study examines the effects of malnutrition on IL-6 signaling pathways of rats fed 2% vs. 20% casein diets for 14 days. Effects of malnutrition on the abundance and IL-6-stimulated phosphorylation of signaling proteins in the JAKSTAT and MAP kinase pathways were examined in the liver. Changes of the acute-phase response as reflected by serum [[alpha].sub.1]-acid glycoprotein (AG), TNF-[alpha] (TNF), and IL-1[beta] (IL-1) were compared in the two dietary groups at 0, 4, 8, 16, and 24 h after IL-6 administration. Under basal conditions, the abundance of the IL-6 receptor, gpl30, JAK1, STATI, and STAT3 proteins and levels of phosphorylation of ERK1/2 and p38 were significantly increased in the liver in the 2% casein group compared with the 20% casein group. With IL-6 stimulation, the increased phosphorylation per unit of protein of these signaling proteins was not different in the liver between the two groups. Before IL-6 stimulation, serum levels of TNF, IL-1, IL-6, and AG were significantly higher in the 2% casein group than in the 20% casein group. After bolus injection of IL-6, changes in IL-1 and AG were similar in the two dietary groups, although a slight decline in AG level was noted after 8 h of IL-6 administration in the 2% protein group. These data demonstrate that protein malnutrition produces changes in inflammation-related proteins characteristic of a low-grade systemic inflammatory response and, thus, can serve as an inflammatory stimulus. The capacity for response to IL-6 is preserved, suggesting adaptive preservation of acute-phase responsiveness during malnutrition. protein-calorie malnutrition; [[alpha].sub.1]-acid glycoprotein; tumor necrosis factor-a; interleukin-1[beta]; immune function; acute phase response

Published
2004

25. Mechanisms of host wasting induced by administration of cytokines in rats

Author

Ling, Pei Ra, Schwartz, Joseph H., and Bistrian, Bruce R.

Subjects
Tumor necrosis factor -- Physiological aspects, Interleukin-1 -- Physiological aspects, Malnutrition -- Physiological aspects, Cytokines -- Physiological aspects, Anorexia nervosa -- Physiological aspects, Rats as laboratory animals -- Physiological aspects, Biological sciences
Abstract

The role of tumor necrosis factor (TNF) on muscle catabolism was analyzed in rat chronic infusion models and semistarved control groups. Continuous infusion of interleukin-1 (IL-1) in rats followed by the administration of TNF enhanced the catabolism of muscle protein which led to chronic weight loss, nitrogen loss and increased liver mass. The effects of TNF and IL-1 were independent from the effects of semistarvation indicating the role of the cytokines in the development of protein calorie malnutrition.

Published
1997

26. Protein and lipid refeeding changes protein metabolism and colonic but not small intestinal morphology and protein-depleted rats

Author

Qu, Zhensheng, Ling, Pei Ra, Tahan, Steven R., Sierra, Pilar, Onderdonk, Andrew B., and Bistrian, Bruce R.

Subjects
Protein metabolism -- Research, Rats -- Food and nutrition, Gastrointestinal mucosa -- Physiological aspects, Proteins in animal nutrition -- Research, Food/cooking/nutrition
Abstract

In this study, we fed rats a 2% casein AIN 76 diet for 2 wk to produce protein malnutrition. We determined in these animals the effects of different concentrations of dietary protein refeeding (2% and 20% casein) on recovery and gut mucosal repletion and the potential role of type of dietary fat in the regulation of protein metabolism and mucosal growth by providing conventional long-chain triglyceride (LCT), a structured lipid composed of long-, medium- and short-chain fatty acids (SC/SL), or a physical mixture of the same components present in the structured lipid given as individual pure triglycerides (SC/PM) along with adequate amounts of protein and energy. The results confirmed that protein malnutrition can be reversed rapidly by protein refeeding, as indicated by an increase in body weight, positive nitrogen balance, liver growth and elevations in plasma concentrations of insulin-like growth factor-1, leucine and albumin. in the colon, crypt cell number, crypt depth and number of crypt cells in the rapidly proliferating fraction of the colon were greater in rats fed the higher protein diet. However, the general architecture of small intestinal mucosa, including duodenum, jejunum and ileum, was not affected by protein malnutrition. Although the number of colonic cells was similar with fat refeeding, there were significantly fewer displaying the proliferating cell nuclear antigen in the colonic epithelium when rats were fed SC/PM compared with SC/SL. Therefore, changes in colonic mucosal proliferation were only seen with repletion by adequate protein and by SC/SL feeding. J. Nutr. 126: 906-912, 1996. INDEXING KEY WORDS: protein depletion, refeeding, intestinal mucosa, structured lipid, short-chain fatty acids, rats

Published
1996

27. Metabolic changes in rats during a continuous infusion of recombinant interleukin-1

Author

Ling, Pei Ra, Schwartz, Joseph H., Jeevanandam, Malayappa, Gauldie, Jack, and Bistrian, Bruce R.

Subjects
Rats -- Physiological aspects, Interleukin-1 -- Physiological aspects, Malnutrition -- Physiological aspects, Biological sciences
Abstract

The hypothesis that recombinant interleukin-1 (IL-1) could induce weight loss and nitrogen loss in rats was tested by varying the dosage of IL-1 under stable nutritional conditions. Rats infused with high IL-1 dose showed higher temperature, plasma levels of IL-6, acute-phase protein production, decreased food intake and the circulating zinc level. Semistarved animals showed more pronounced changes, suggesting that IL-1 regulates body mass in rats.

Published
1996

29. Differential effects of interleukin-1 receptor antagonist in cytokine- and endotoxin-treated rats

Author

Ling, Pei Ra, Istfan, Nawfal W., Colon, Eric, and Bistrian, Bruce R.

Subjects
Interleukin-1 -- Physiological aspects, Metabolism -- Research, Biological sciences
Abstract

Experimental studies of rats treated with cytokines such as tumor necrosis factor and interleukin-1 (IL-1) and those treated with endotoxins suggest an enhancement of plasma insulin, resistance to insulin, glucose flux in fed state and decrease in plasma zinc in injured state due to IL-1. The response of these rats to endotoxins or cytokines in relation to protein metabolism is complex and varies with food content in the body. These impairments during metabolism can be rectified by using the IL-1 receptor antagonist, in conjunction with a proper nutritional diet.

Published
1995

31. Patterns of plasma leptin and insulin concentrations in hospitalized patients after the initiation of total parenteral nutrition

Author

McCowen, Karen C, Ling, Pei Ra, Friel, Charles, Sternberg, Jeffrey, Forse, R Armour, Burke, Peter A, and Bistrian, Bruce R

Subjects
Leptin -- Health aspects, Parenteral feeding -- Health aspects, Critically ill -- Food and nutrition, Food/cooking/nutrition, Health
Abstract

Background: The regulation of leptin in patients with critical illness is poorly understood. Sex, diet, body mass, and cytokines may all play a role. Objective: The aims of this study were to determine the factors influencing leptin concentrations in hospitalized patients beginning total parenteral nutrition (TPN) and whether a 3-d regimen of TPN would further increase plasma leptin concentrations above baseline. Design: Twenty-six patients requiring TPN were enrolled in this prospective, nonintervention study. Only 20 (11 women and 9 men) completed all 3 d of TPN. Results: Baseline plasma leptin in the TPN patients ranged from 62.5 to 1625 pmol/L ([bar] [+ or -] SD: 419 [+ or -] 387; n = 26) and was not significantly different between men (444 [+ or -] 494 pmol/L) and women (363 [+ or -] 244 pmol/L). Baseline plasma insulin ranged from 76 to 695 pmol/L (271 [+ or -] 188; n = 26) and was not correlated with plasma leptin. Leptin concentrations increased after 3 d of TPN, from 356 [+ or -] 300 to 794 [+ or -] 600 pmol/L (P < 0.05) in parallel with an increase in insulin from 257 [+ or -] 187 to 979 [+ or -] 917 pmol/L (P < 0.01) in the 20 patients who completed the study; however, the changes were not correlated when expressed as percentages. Although the men and women had insulin responses to feeding that were not significantly different, leptin concentrations did not increase significantly in men but increased 3-fold in women (to 1094 [+ or -] 638 pmol/L; P < 0.01). Conclusions: Leptin regulation in patients with a critical illness differs substantially from that in healthy persons. The importance of glucose and insulin in leptin secretion remains unclear, especially in men. KEY WORDS Total parenteral nutrition, TPN, leptin, insulin, fasting, critical illness, cytokines, sex differences, body mass

Published
2002

38. IGF-I alters energy expenditure and protein metabolism during parenteral feeding in rats

Author

Ling, Pei Ra, Gollaher, Catherine, Istfan, Nawfal, and Bistrian, Bruce R.

Subjects
Insulin-like growth factor 1 -- Health aspects, Protein metabolism -- Measurement, Glucose metabolism -- Measurement, Energy metabolism -- Measurement, Food/cooking/nutrition, Health
Abstract

In this study, 20 [micro]g * [kg *.sup.-1] * [h.sup.-1] of recombinant human insulin-like growth factor I (IGF-I) was infused into normal healthy rats to examine the effects of IGF-I on glucose, protein, and energy metabolism in either overnightfasting or parenteral-feeding states. The fed state was maintained by continuous intravenous feeding of a complete diet containing 838 kJ * [kg.sup.-1] * [d.sup.-1], 2 g N * [kg.sup.-1] * [d.sup.-1], and no fat. At each nutritional state, one-half of the animals received IGF-I infusion while the other half received saline as control. [[.sup.14C]-1]leucine and [[.sup.3H]-6]glucose were used to determine the effects of IGF-I on protein and glucose kinetics during fed and fasting states. The results showed that 1) infusion of IGF-I at this amount did not alter plasma glucose appearance and only marginally decreased plasma glucose concentrations in both nutritional states; 2) during fasting, IGF-I did not show anabolic effects on protein metabolism either at the whole-body level or in individual tissues. However, during feeding, IGF-I significantly stimulated exogenous nitrogen utilization by the whole body; and 3) IGF-I reduced the thermogenic effect of feeding. The results suggest that parenteral feeding may be an important variable in the response of protein anabolism to IGF-I in vivo.

Published
1995

42. Overweight and stunting in migrant Hispanic children in the USA

Author

You, Tongjian, Yang, Rongze, Lyles, Mary F, Gong, Dawei, Nicklas, Barbara J, Wells, Jonathan C K, Weise, Antonio Suarez, Warner, Matthew J, Ozanne, Susan E, Visser, Marjolein, Bouter, Lex M, McQuillan, G. M., Wener, Mark H, Harris, Tamara B, Tzioumis, Emma, Adair, Linda S., Snell-Bergeon, Janet K., West, Nancy A, Mayer-Davis, Elizabeth J., Liese, Angela D, Marcovina, Santica M, D'Agostino, Ralph B., Hamman, Richard F, Dabelea, Dana, Sawaya, Ana Lydia, Roberts, Susan B, Prendergast, Andrew J, Humphrey, Jean H, Packard, René R S, Libby, Peter, Nakayama, Tomohiro, Wang, Zhaoxia, Mukuddem-Petersen, J, Kruger, Herculina Salome, Motie, Marjan, Evangelista, Lorraine S, Horwich, Tamara, Lombardo, Dawn, Zaldivar, Frank, Hamilton, Michele, Fonarow, Gregg C, Mcdade, Thomas W., Tallman, Paula S., Madimenos, Felicia C., Liebert, Melissa A., Cepon, Tara J., Sugiyama, Lawrence S., Snodgrass, James Josh, Martins, Paula A, Hoffman, Daniel J, Fernandes, M T B, Nascimento, C R, Sesso, R, Markowitz, Diane L, Cosminsky, Sheila, Ridker, Paul M., Maseri, Attilio, Pretorius, Rachelle, Schutte, Aletta E, Kimani-Murage, Elizabeth W., Kahn, Kathleen, Pettifor, John M, Tollman, Stephen M, Dunger, David B, Gómez-Olivé, Xavier F., Norris, Shane A, Khaodhiar, Lalita, Ling, Pei-Ra, Blackburn, George L, Bistrian, Bruce R, Jinabhai, C C, Taylor, M, Sullivan, K R, Herder, Christian, Schneitler, Sophie, Rathmann, Wolfgang, Haastert, Burkhard, Schneitler, Heiko, Winkler, Horst, Bredahl, Renate, Hahnloser, Erik, Martin, Stephan, Filla, Putu, Fernald, L C, Neufeld, L M, and Moral and Political Philosophy

Subjects
Leptin, Male, Dual-e, food intake, a obesidade vem aumentando, poverty, Inflammation: epidemiology, Developmental Disabilities, nutrition disorders, mostrando que a, Blood Pressure, South Africa: epidemiology, Comorbidity, Global Health, complications [Malnutrition], Body Mass Index, Pregnancy, Reference Values, nutrition transition, blood [Interleukin-6], Prospective Studies, Child, Children, Growth Disorders, metabolism [Inflammation], Stunting, Schools, iotf, Anthropometry, Statistics, complications [Obesity], blood [Tumor Necrosis Factor-alpha], prevention & control [Developmental Disabilities], prevention & control [Obesity], who, Obesity: epidemiology, C-Reactive Protein, nutrition, Adipose Tissue, african primary school children, analysis [C-Reactive Protein], Body Composition, early growth, Obesity: metabolism, Economic deprivation, metabolism [Intra-Abdominal Fat], o risco de obesidade, futura, socio-economic status, metabolism [C-Reactive Protein], Heart failure, physiology [Body Composition], epidemiology [South Africa], mas também nos países, Humans, Nonparametric, Endothelium, Developing Countries, Adipose Tissue: anatomy & histology, analysis [Biological Markers], Developmental Disabilities: prevention & control, Tumor Necrosis Factor-alpha, Infant, Proteins, C-Reactive Protein: analysis, Tumor Necrosis Factor-alpha: blood, diagnosis [Obesity], Confounding Factors (Epidemiology), United States, diagnosis [Inflammation], nutritional status, Cross-Sectional Studies, C-Reactive Protein: metabolism, Social Class, income countries, Case-Control Studies, Linear Models, complications [Growth Disorders], metabolism [Adipose Tissue], anatomy & histology [Adipose Tissue], atherosclerosis, Agricultural laborers, Biomarkers, Body Height: physiology, double burden, obesity, Intra-Abdominal Fat: metabolism, Growth, Developmental Disabilities: epidemiology, Body Composition: physiology, Growth Disorders: complications, Adipose Tissue: metabolism, Leukocyte Count, South Africa, hs-crp, Risk Factors, Biological Markers: analysis, metabolism [Growth Disorders], epidemiology [Developmental Disabilities], Cluster Analysis, epidemiology [Growth Disorders], maternal diet, Interleukin-6: blood, dual burden, indigenous, não apenas nos países, significativa de evidências epidemiológicas, low- and middle, thrifty phenotype, physiology [Body Height], Photon, Growth Disorders: epidemiology, Plethysmography, Obesity: prevention & control, nutritional transition, Biological Markers, Female, hypothesis, Disease Susceptibility, epidemiology [United States], type 2 diabetes, dramaticamente, Brazil, em desenvolvi, Adult, Malnutrition: complications, epidemiology [Inflammation], Adolescent, United States: epidemiology, Obesity: complications, complications [Inflammation], Intra-Abdominal Fat, Migrants, Obesity: diagnosis, Young Adult, Inflammation: metabolism, Sex Factors, overnutrition, metabolism [Obesity], overweight, Absorptiometry, coronary heart disease, Preschool, Inflammation, pre-school, epidemiology [Obesity], urbanisation, resumo existe uma quantidade, Height, Interleukin-6, menarche, Body Weight, Malnutrition, Undernutrition, Newborn, Body Height, desenvolvidos, Inflammation: complications, Chronic Disease, Growth Disorders: metabolism, Insulin Resistance, Inflammation: diagnosis, Follow-Up Studies, baixa estatura nutricional aumenta
Abstract

Obesity, type 2 diabetes mellitus (DM) and metabolic syndrome (MS) are common in patients with heart failure (HF). Studies investigating the association between known biomarkers and adiposity in patient populations are limited. The aim of the present study was to investigate the association between C-reactive protein (CRP) and leptin with adiposity in a sub-group of overweight/obese patients with HF, DM and/or MS. A total of 36 patients (mean age, 56.72±9.78 years; ranging between 27 and 76 years of age; 80.6% male; 52.8% Caucasian) were enrolled and their height, weight, waist circumference and body composition (e.g. percentage body fat and lean mass), as well as the levels of CRP and leptin, were assessed. The results demonstrated that there was a significant association between CRP and leptin, CRP and body mass index (BMI) and gender and percentage body fat (P

Published
2010

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