RESUMO
Protein supplementation may be beneficial for patients with chronic liver disease (CLD). This study compared the effects of whey protein isolate (WP) and casein (CA) supplementation on nutritional status and immune parameters of CLD patients who were randomly assigned to take 20 g of WP or CA twice per d as a supplement for 15 d. Body composition, muscle functionality and plasmatic immunomarkers were assessed before and after supplementation. Patients were also classified according to the model for end-stage liver disease (MELD) into less (MELD < 15) and more (MELD ≥ 15) severe disease groups. Malnutrition, determined by the Subjective Global Assessment at baseline, was observed in 57·4 % and 54·2 % of patients in the WP and CA groups, respectively (P = 0·649). Protein intake was lower at baseline in the WP group than in the CA group (P = 0·035), with no difference after supplementation (P = 0·410). Both the WP and CA MELD < 15 groups increased protein intake after supplementation according to the intragroup analysis. No differences were observed in body composition, muscle functionality, most plasma cytokines (TNF, IL-6, IL-1ß and interferon-γ), immunomodulatory proteins (sTNFR1, sTNFR2, brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor) or immunomodulatory hormones (adiponectin, insulin and leptin) after supplementation in the WP groups at the two assessed moments. WP supplementation increased the levels of interferon-γ-induced protein-10/CXCL10 (P = 0·022), eotaxin-1/CCL11 (P = 0·031) and monocyte chemoattractant protein-1/CCL2 (P = 0·018) and decreased IL-5 (P = 0·027), including among those in the MELD ≥ 15 group, for whom IL-10 was also increased (P = 0·008). Thus, WP consumption by patients with CLD impacted the immunomodulatory responses when compared with CA with no impact on nutritional status.
RESUMO
The aim of this work was to study the effect of the administration of cod liver oil on the non-oxidative and oxidative fate of glucose metabolism in the skeletal muscle of normal rats. To achieve this goal, the gastrocnemius was examined regarding glucose oxidation, glycogen synthase activity and glycogen storage both at baseline and during euglycemic hyperinsulinemic clamping. The results show that dietary fish oil decreases plasma insulin levels without alteration in glucose homeostasis (at baseline). In addition, the observed enhancement in whole body glucose utilization during clamping suggests an increased peripheral insulin sensitivity. Furthermore, under insulin-stimulated glucose disposal, an enhancement in the glycolytic pathway (increased levels of muscle glucose-6-phosphate and plasma lactate) rather than changes in the oxidation (pyruvate dehydrogenase complex) and storage components of glucose metabolism was observed in the skeletal muscle of rats fed dietary fish oil. These results coupled with the hypolipidemic effects of fish oil may have implications for the prevention and/or management of some pathological states manifested by insulin resistance with or without dyslipidemia.
Assuntos
Gorduras Insaturadas na Dieta/farmacologia , Óleos de Peixe/farmacologia , Glucose/metabolismo , Insulina/metabolismo , Músculo Esquelético/fisiologia , Animais , Óleo de Fígado de Bacalhau/farmacologia , Óleo de Milho/farmacologia , Ácidos Graxos/administração & dosagem , Técnica Clamp de Glucose , Glucose-6-Fosfato/metabolismo , Glicogênio/metabolismo , Glicogênio Sintase/efeitos dos fármacos , Masculino , Proteínas Quinases/efeitos dos fármacos , Proteínas Serina-Treonina Quinases , Piruvato Desidrogenase Quinase de Transferência de Acetil , Complexo Piruvato Desidrogenase/efeitos dos fármacos , Ratos , Ratos Wistar , Valores de Referência , Triglicerídeos/metabolismoRESUMO
In this work, we studied the effect of a short-term (3 wk) and a long-term (15 wk) administration of a sucrose-rich diet (SRD) to Wistar rats on the morphological aspects and metabolic function of the epididymal adipose tissue that may contribute to the mechanism underlying the impaired glucose homeostasis and insulin resistance. The present work showed the following. 1) There was both a moderate increase of basal lipolysis and a decrease of the antilipolytic action of insulin in the adipocytes of rats fed a SRD for 3 wk. Neither size alterations nor increases in adipose tissue mass were recorded in this period. 2) There was a significant (P < 0.05) increase of epididymal weight after 15 wk on a SRD as well as a hypertrophy of adipocytes with a clear alteration in the cell size distribution. This was accompanied by a significant increase (P < 0.05) of basal and stimulated lipolysis and a marked decrease (P < 0.05) of the antilipolytic action of insulin. Moreover, these changes appear together with a worsening of both impaired glucose homeostasis and insulin resistance. Our results also indicate that the length of time on the SRD plays an important role in the evolution of the adiposity and metabolic changes observed in the fat pad. Furthermore, the latter precedes the detection of adiposity.
Assuntos
Adipócitos/efeitos dos fármacos , Sacarose/farmacologia , Adipócitos/metabolismo , Adipócitos/ultraestrutura , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/fisiologia , Animais , Contagem de Células , Dieta , Ingestão de Alimentos , Técnica Clamp de Glucose , Glicerol/metabolismo , Hiperinsulinismo/metabolismo , Técnicas In Vitro , Resistência à Insulina/fisiologia , Lipase Lipoproteica/metabolismo , Masculino , Tamanho do Órgão/fisiologia , Ratos , Ratos Wistar , Esterol Esterase/metabolismo , Aumento de Peso/fisiologiaRESUMO
In the present study we investigated: (1) the contribution of the skeletal muscle to the mechanisms underlying the impaired glucose homeostasis and insulin sensitivity present in dyslipemic rats fed a sucrose-rich diet (SRD) over a long period of time and (2) the effect of fish oil on these parameters when there was a stable hypertriglyceridemia before the source of fat (corn oil) in the diet was replaced by isocaloric amounts of cod liver oil. Our results show an increased triglyceride content in the gastrocnemius muscle with an impaired capacity for glucose oxidation in the basal state and during euglycemic clamp. This was mainly due to a decrease of the active form of pyruvate dehydrogenase complex (PDHa) and an increase of PDH kinase activities. Hyperglycemia, normoinsulinemia, and diminished peripheral insulin sensitivity also were found. Even though there were no changes in the insulin levels, the former metabolic abnormalities were completely reversed when the source of fat was changed from corn oil to cod liver oil. The data also suggest that in the gastrocnemius muscle of rats fed a SRD over an extended period, an increased availability and oxidation of the lipid fuel, which in turn impairs the glucose oxidation, contributes to the abnormal glucose homeostasis and to the peripheral insulin insensitivity. Moreover, the parallel effect on insulin sensitivity, glucose, and lipid homeostasis attained through the manipulation of dietary fat (n-3) in the SRD suggests a role of n-3 fatty acid in the management of dyslipidemia and insulin resistance.
RESUMO
Rats chronically fed (15 weeks) a sucrose-rich diet (SRD) developed hypertriglyceridemia (hyperTg), increased plasma free fatty acids (FFA), impaired glucose homeostasis and insulin insensitivity. An increase of Tg and glycogen (Gly) in heart muscle was also observed. HyperTg with altered glucose metabolism could have profound effects on myocardial glucose utilization. To test this hypothesis male Wistar rats were fed a semi-synthetic SRD (w/w: 62.5% sucrose, 8% corn-oil, 17% protein), and the control group (CD) received the same semi-synthetic diet, except that sucrose was replaced with starch for 90 days. At that time, the hearts from these animals were isolated and perfused for 30 min in the presence or absence of insulin (30 mU/ml). Levels of the exogenous substrates were similar to those found in the plasma of the animal in vivo in both dietary groups (glucose 8.5 mM, palmitate 0.8 mM in SRD and glucose 5-5 mM, palmitate 0.3 mM in CD). In the absence of insulin glucose uptake was reduced (40%) and lactate release was increased (50%) in SRD hearts. Glucose oxidation was depressed mainly due to both, an increase of PDH kinase and a decrease of 60% of PDHa (active form of PDHc). Insulin in the perfusion medium improved only glucose uptake. The results suggest that at least two different mechanisms might contribute to insulin resistance and to impaired glucose metabolism in the perfused hearts of dyslipemic SRD fed rats: 1) reduced basal and insulin-stimulated glucose uptake and its utilization and 2) increased availability and oxidation of lipids (low PDHa and PDH kinase activities), which in turn decreased glucose uptake and utilization. Thus, this experimental model may be useful to study how impaired glucose homeostasis, increased plasma FFA and hyperTg could contribute to heart tissue malfunction.
Assuntos
Glucose/metabolismo , Hiperlipidemias/metabolismo , Insulina/fisiologia , Miocárdio/metabolismo , Análise de Variância , Animais , Modelos Animais de Doenças , Ácidos Graxos/metabolismo , Resistência à Insulina , Masculino , Miocárdio/enzimologia , Complexo Piruvato Desidrogenase/metabolismo , Piruvato Quinase/metabolismo , Ratos , Ratos Wistar , Aumento de PesoAssuntos
Códon , Síndrome de Creutzfeldt-Jakob/genética , Mutação Puntual , Chile , Feminino , Humanos , Pessoa de Meia-Idade , LinhagemRESUMO
The aim of this study was to investigate the relationship between the lipid-lowering effects of fish oils and concomitant consequences on glucose tolerance and insulin sensitivity in an experimental animal model of hypertriglyceridemia induced by high sucrose intake. To achieve this goal, male Wistar rats were fed a semi-synthetic sucrose rich diet (SRD) (w/w: 62.3% sucrose, 8% corn oil, 17% protein) for 90 days. At the time, a well established and permanent hypertriglyceridemia accompanied by glucose intolerance was present. After that, one half of the animals continued on the SRD up to 120 days. The other half received an SRD in which the source of fat was substituted by cod liver oil (w/w 7% CLO plus 1% corn oil) from day 90 to 120 (SRD+CLO). Control rats were fed a semi-synthetic diet (CD) (w/w: 62.5% corn starch, 8% corn oil, 17% protein) throughout the 120 days experimental period. Results obtained after the experimental period show that the hypertriglyceridemia and glucose intolerance ensuing long term feeding normal rats with a sucrose-rich diet could be completely reversed mediating no change in circulating insulin levels by shifting the source of fat in the diet from corn oil to cod liver oil. These findings suggest that manipulation of dietary fats may play a role in the management of the lipid disorders associated with glucose intolerance and insulin resistance.
Assuntos
Óleo de Fígado de Bacalhau/uso terapêutico , Carboidratos da Dieta , Gorduras Insaturadas na Dieta/uso terapêutico , Intolerância à Glucose/tratamento farmacológico , Glucose , Hiperlipidemias/tratamento farmacológico , Triglicerídeos/sangue , Animais , Glicemia , Peso Corporal , Ingestão de Alimentos , Emulsões Gordurosas Intravenosas/administração & dosagem , Intolerância à Glucose/induzido quimicamente , Teste de Tolerância a Glucose , Hiperlipidemias/induzido quimicamente , Insulina/sangue , Resistência à Insulina , Fígado/metabolismo , Masculino , Ratos , Ratos Wistar , Triglicerídeos/análiseRESUMO
The effect of omega-3 fatty acids derived from fish and marine mammals on subjects with normal glucose tolerance is still unclear. The aim of the present study was to test whether the hypolipidemia that follows the chronic administration of cod liver oil, rich in polyunsaturated fatty acids (omega-3), to normal rats is accompanied by changes in glucose metabolism, insulin secretion and sensitivity, and pancreatic insulin content. To achieve this goal, male Wistar rats were fed with a semisynthetic diet (w/w): 62.5% cornstarch, 7% cod liver oil plus 1% corn oil, and 17% protein (CD + CLO). Control rats were fed with the same semisynthetic diet with the only exception that the source of fat was 8% (w/w) corn oil (CD). Both diets were administered ad libitum for 1 month. At the end of the experimental period, the results obtained were as follows (mean +/- SEM): serum triacylglycerol (mM): CD + CLO 0.21 +/- 0.04 vs. CD 0.58 +/- 0.05 (p < 0.05); free fatty acids (microM): CD + CLO 257 +/- 20 vs. CD 288 +/- 22 (p = NS); total cholesterol (mM): CD + CLO 1.13 +/- 0.09 vs. CD 1.82 +/- 0.06 (p < 0.05); high-density lipoprotein cholesterol (mM): CD + CLO 0.58 +/- 0.08 vs. CD 1.07 +/- 0.04 (p < 0.05); plasma glucose (mM): CD + CLO 6.30 +/- 0.29 vs. CD 6.28 +/- 0.10 (p = NS); liver triacylglycerol (mumol/liver): CD + CLO 104.1 +/- 11.4 vs. CD 136.8 +/- 4.3 (p < 0.05); glycogen (mumol/g wet weight): CD + CLO 298.3 +/- 21.0 vs. CD 297.0 +/- 19.0 (p = NS); glucose-6-phosphate dehydrogenase (U/liver): CD + CLO 37.9 +/- 2.2 vs. CD 58.8 +/- 5.0 (p < 0.05); triacylglycerol secretion (nmol/min/100 g body weight): CD + CLO 101.0 +/- 2.0 vs. CD 166.0 +/- 9.7 (p < 0.01); removal of fat emulsion (K2% min-1): CD + CLO 15.0 x 10(-2) +/- 0.8 x 10(-2) vs. CD 8.2 x 10(-2) +/- 0.2 x 10(-2) (p < 0.01); intravenous glucose tolerance (kg 10(-2): CD + CLO 2.68 +/- 0.37 vs. CD 2.70 +/- 0.14 (p = NS); immunoreactive insulin (microU/ml/ min): with the area under the curve between 0 and 30 min CD + CLO 544 +/- 60 vs. CD 1,050 +/- 38 (p < 0.05), with the area under the curve between 0 and 60 min CD + CLO 1,188 +/- 150 vs. CD 2,160 +/- 137 (p < 0.05), and pancreas insulin content (microU/mg pancreas): CD + CLO 1.85 +/- 0.29 vs. CD 2.04 +/- 0.12 (p = NS). In conclusion, the present study shows that the strong hypolipidemic effect produced by the administration of low doses of fish oil to normal rats is accompanied by a significant reduction of plasma insulin levels without changes in glucose tolerance. Since no changes in pancreatic insulin content were observed, lower plasma insulin levels, both basal and after an intravenous glucose challenge, may be the result of an increased peripheral insulin sensitivity in normoglycemic animals.