RESUMO
The isomer-specific effects of conjugated linoleic acid (CLA) on hepatic steatosis were assessed in fa/fa Zucker rats, a model for insulin resistance and the metabolic syndrome. Eight weeks of feeding trans-10,cis-12 CLA significantly improved glucose tolerance without changing body weight or visceral adipose mass. The trans-10,cis-12 isomer was also associated with reduced liver lipid content, improved liver function and reduced inflammation; these effects were not observed in rats fed the cis-9,trans-11 CLA isomer. Reduced liver lipid content did not correlate with activation of AMP-activated protein kinase or suppressed activation of sterol-regulatory element binding protein-1, two key regulators of hepatic lipid metabolism. Interestingly, rats fed cis-9,trans-11 CLA had fewer cytoplasmic lipid droplets in hepatocytes compared to rats fed control diet, but these droplets were larger in size. Conversely, fa/fa rats fed the trans-10,cis-12 CLA isomer had greater numbers of hepatic lipid droplets that were smaller in size, resulting in overall lower total lipid within these droplets. Changes in lipid droplets were associated with lower hepatic levels of PERILIPIN-2 (formerly known as adipophilin) in rats fed trans-10,cis-12 CLA, whereas amounts of other members of the PERILIPIN family of lipid droplet proteins were unaffected by dietary CLA. However, CLA isomers differentially affected the subcellular localization of these proteins. Treatment of H4IIE rat hepatoma cells with CLA isomers neither prevented nor reversed, but rather induced cytoplasmic lipid droplet formation, suggesting that the anti-steatotic effects of trans-10,cis-12 CLA are likely indirect and potentially mediated via increased lipid utilization by peripheral tissues.
Assuntos
Fígado Gorduroso/metabolismo , Resistência à Insulina , Ácidos Linoleicos/metabolismo , Metabolismo dos Lipídeos , Obesidade/metabolismo , Animais , Fígado Gorduroso/complicações , Obesidade/complicações , RatosRESUMO
OBJECTIVE: To determine the effects of dietary consumption of milled flaxseed or flaxseed oil on glycemic control, n-3 fatty acid status, anthropometrics, and adipokines in individuals with type 2 diabetes. DESIGN: Thirty-four participants were randomized into a parallel, controlled trial. SUBJECTS: The participants were adults with type 2 diabetes (age 52.4 +/- 1.5 years, body mass index 32.4 +/- 1.0 kg/m(2), n = 17 men and 17 women). INTERVENTIONS: Participants consumed a selection of bakery products containing no flax (control group [CTL], n = 9), milled flaxseed (FXS, n = 13; 32 g/d), or flaxseed oil (FXO, n = 12; 13 g/d) daily for 12 weeks. The FXS and FXO groups received equivalent amounts of alpha-linolenic acid (ALA; 7.4 g/day). MEASURES OF OUTCOME: The primary outcome measures were fasting plasma hemoglobin A(1c), glucose, insulin, and phospholipid fatty acid composition. The secondary outcome measures were fasting circulating leptin and adiponectin, as well as body weight, body mass index, and waist circumference. Dietary intake assessment and calculations for homeostasis model assessment for insulin resistance and quantified insulin sensitivity check were also completed. RESULTS: The FXS and FXO groups had increases in plasma phospholipid n-3 fatty acids (ALA, eicosapentaenoic acid [EPA], or decosapentaenoic acid [DPA], but not docosahexaenoic acid), and the FXO group had more EPA and DPA in plasma phospholipids compared to the FXS group. All groups had similar caloric intakes; however, the CTL group experienced a 4% weight gain compared to baseline (p < 0.05), while both flax groups had constant body weights during the study period. All other parameters, including glycemic control, were unchanged by dietary treatment. CONCLUSIONS: Milled FXS and FXO intake does not affect glycemic control in adults with well-controlled type 2 diabetes. Possible prevention of weight gain by flax consumption warrants further investigation.
Assuntos
Peso Corporal/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Gorduras na Dieta/metabolismo , Ácidos Graxos Ômega-3/sangue , Linho/química , Óleo de Semente do Linho/uso terapêutico , Preparações de Plantas/uso terapêutico , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Ácidos Docosa-Hexaenoicos/sangue , Ácido Eicosapentaenoico/sangue , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Ômega-3/uso terapêutico , Feminino , Índice Glicêmico , Humanos , Óleo de Semente do Linho/farmacologia , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Fosfolipídeos/sangue , Fosfolipídeos/química , Fitoterapia , Preparações de Plantas/farmacologia , Sementes , Ácido alfa-Linolênico/farmacologia , Ácido alfa-Linolênico/uso terapêuticoRESUMO
OBJECTIVE: To evaluate cardiovascular disease risk in First Nation youth with and without type 2 diabetes mellitus (T2DM) or obesity by comparing pro- and anti-inflammatory adipokines, markers of oxidative stress and the plasma phospholipid fatty acid profile. METHOD: Self-declared First Nation youth (12-15 yr) with T2DM (n = 24) as well as age-, gender-, and body mass index-matched controls (obese group; n = 19) and unmatched controls (control group; n = 34) were recruited from a pediatric diabetes clinic. RESULTS: Plasma tumor necrosis factor-alpha, ultrasensitive C-reactive protein, resistin, and total antioxidant status were not different among the three groups. Plasma total leptin, soluble leptin receptor, and free leptin were significantly higher in the T2DM group than the control group (p < 0.001, p = 0.019, p < 0.001, respectively) but did not differ from the obese group. Similarly, oxidized low-density lipoprotein was higher in the T2DM group compared with controls (p = 0.002) but not in the obese group. However, interleukin-6 was significantly higher (p < 0.001) in the T2DM group compared with both the control and the obese groups, suggesting that T2DM, but not an increase in adiposity, was responsible for this elevation. Adiponectin was significantly lower in the T2DM group compared with the control group only (p = 0.035). CONCLUSIONS: Changes in plasma adipokines and oxidative stress can already be detected in youth with T2DM; however, many of the changes are mirrored in obese youth, suggesting that both these populations are at an increased risk for future cardiovascular complications.
Assuntos
Adipocinas/sangue , Biomarcadores/sangue , Doenças Cardiovasculares/etiologia , Diabetes Mellitus Tipo 2/complicações , Obesidade/complicações , Estresse Oxidativo/fisiologia , Adolescente , Antioxidantes/análise , Canadá/epidemiologia , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , Estudos de Casos e Controles , Criança , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Humanos , Mediadores da Inflamação/sangue , Obesidade/sangue , Obesidade/epidemiologia , Fatores de RiscoRESUMO
Abnormal expression and/or function of mammalian hexose transporters contribute to the hallmark hyperglycemia of diabetes. Due to different roles in glucose handling, various organ systems possess specific transporters that may be affected during the diabetic state. Diabetes has been associated with higher rates of intestinal glucose transport, paralleled by increased expression of both active and facilitative transporters and a shift in the location of transporters within the enterocyte, events that occur independent of intestinal hyperplasia and hyperglycemia. Peripheral tissues also exhibit deregulated glucose transport in the diabetic state, most notably defective translocation of transporters to the plasma membrane and reduced capacity to clear glucose from the bloodstream. Expression of renal active and facilitative glucose transporters increases as a result of diabetes, leading to elevated rates of glucose reabsorption. However, this may be a natural response designed to combat elevated blood glucose concentrations and not necessarily a direct effect of insulin deficiency. Functional foods and nutraceuticals, by modulation of glucose transporter activity, represent a potential dietary tool to aid in the management of hyperglycemia and diabetes.
Assuntos
Diabetes Mellitus/metabolismo , Proteínas Facilitadoras de Transporte de Glucose , Glucose/metabolismo , Hiperglicemia/metabolismo , Resistência à Insulina/fisiologia , Animais , Humanos , Insulina/metabolismo , CamundongosRESUMO
PURPOSE: In healthy participants and those with diet-controlled type 2 diabetes (T2DM), to (1) compare the acute 3-hour post-prandial response of glucose, insulin and other gastrointestinal hormones known to influence food intake and glucose metabolism after consumption of a food product made from whole grain buckwheat flour versus rice flour; (2) determine the effect of daily consumption of a food product made from whole grain buckwheat flour on fasting glucose, lipids and apolipoproteins. METHODS: Healthy participants or those with T2DM consumed either buckwheat or rice crackers. Blood samples were collected at baseline and 15, 30, 45, 60, 120 and 180minutes after consumption. In a second phase of the study, participants consumed one serving of buckwheat crackers daily for 1week; fasting blood samples from day 1 and day 7 were analyzed. RESULTS: Post-prandial plasma glucagon-like peptide-1, glucose-dependent insulinotropic peptide and pancreatic polypeptide were altered after consuming buckwheat versus rice crackers. Interestingly, changes in these hormones did not lead to changes in post-prandial glucose, insulin or C-peptide concentrations. Significant correlations were observed between both fasting concentrations and post-prandial responses of several of the hormones examined. Interestingly, certain correlations were present only in the healthy participant group or the T2DM group. There was no effect of consuming buckwheat for one week on fasting glucose, lipids or apolipoproteins in either the healthy participants or those with T2DM. CONCLUSIONS: Although the buckwheat cracker did not modify acute glycemia or insulinemia, it was sufficient to modulate gastrointestinal satiety hormones.
Assuntos
Diabetes Mellitus Tipo 2/dietoterapia , Fibras na Dieta/uso terapêutico , Fagopyrum/química , Polipeptídeo Inibidor Gástrico/sangue , Peptídeo 1 Semelhante ao Glucagon/sangue , Resposta de Saciedade , Sementes/química , Idoso , Índice de Massa Corporal , Canadá , Estudos Cross-Over , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Feminino , Polipeptídeo Inibidor Gástrico/metabolismo , Trato Gastrointestinal/metabolismo , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Oryza/química , Sobrepeso/complicações , Período Pós-Prandial , Método Simples-CegoRESUMO
Increased adrenergic drive is a major factor influencing the development of pathological cardiac hypertrophy, a stage which precedes overt heart failure. We examined the effect of resveratrol, a polyphenol (found predominantly in grapes), in preventing norepinephrine induced hypertrophy of adult cardiomyocyte, and the role of nitric oxide (NO) and adenosine monophosphate kinase (AMPK) in the effects of resveratrol. Cardiomyocytes isolated from adult rats were pretreated, or not, with resveratrol and then exposed to norepinephrine for 24h. In other experiments cardiomyocytes were also treated with different pharmacological inhibitors of NO synthase, AMPK and sirtuin for elucidating the signaling pathways underlying the effect of resveratrol. In order to validate the role of these signaling molecules in the in vivo settings, we also examined hearts from resveratrol treated spontaneously hypertensive rats (SHR), a genetic model of essential hypertension. Cardiomyocyte hypertrophy was determined by morphometry and (3)H-phenylalanine incorporation assay. NO levels and AMPK activity were measured using a specific assay kit and western blot analysis respectively. In vitro, resveratrol prevented the norepinephrine-induced increase in cardiomyocytes size and protein synthesis. Pharmacological inhibition of NO-AMPK signaling abolished the anti-hypertrophic action of resveratrol. Consistent with the in vitro findings, the anti-hypertrophic effect of resveratrol in the SHR model was associated with increases in NO and AMPK activity. This study demonstrates that NO-AMPK signaling is linked to the anti-hypertrophic effect of resveratrol in adult cardiomyocytes in vitro, and in the SHR model in vivo.
Assuntos
Adenilato Quinase/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Óxido Nítrico/metabolismo , Norepinefrina/farmacologia , Transdução de Sinais/efeitos dos fármacos , Estilbenos/farmacologia , Animais , Tamanho Celular/efeitos dos fármacos , Hipertrofia/induzido quimicamente , Hipertrofia/metabolismo , Hipertrofia/patologia , Hipertrofia/prevenção & controle , Masculino , Miócitos Cardíacos/metabolismo , NG-Nitroarginina Metil Éster/farmacologia , Niacinamida/farmacologia , Biossíntese de Proteínas/efeitos dos fármacos , Pirazóis/farmacologia , Pirimidinas/farmacologia , Ratos , Ratos Endogâmicos SHR , Ratos Sprague-Dawley , Resveratrol , S-Nitroso-N-Acetilpenicilamina/farmacologiaRESUMO
Buckwheat contains d-chiro-inositol (D-CI) and myo-inositol (MI), possible insulin-mimetic compounds; thus, this study investigated the insulin-mimetic activities of a buckwheat concentrate (BWC), D-CI, and MI on insulin signal transduction pathways and glucose uptake with H4IIE rat hepatoma cells. BWC stimulated phosphorylation of p42/44 extracellular-related kinase (p42/44 ERK) and its downstream target, p70(S6K), on Thr(421). In contrast, D-CI, MI, rutin, or its agylcone form, quercetin, did not activate these signal transduction proteins. Phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK), another target of insulin, was also up-regulated upon BWC treatment. The effects of BWC on glucose uptake were subsequently investigated using H4IIE cells. Insulin and D-CI stimulated glucose uptake, whereas BWC inhibited basal and insulin-stimulated glucose uptake. Although results from this work suggest that BWC has insulin-mimetic effects on select protein phosphorylation events in H4IIE cells, D-CI and MI were not the active components responsible for the observed effects. The inhibition of glucose uptake by BWC suggests that buckwheat may affect hepatic glucose metabolism, possibly by inhibiting glucose flux. Furthermore, the fact that D-CI and MI stimulated glucose uptake in H4IIE cells suggests that other compounds are responsible for inhibition of glucose uptake by BWC.
Assuntos
Fagopyrum/química , Inositol/farmacologia , Neoplasias Hepáticas Experimentais/patologia , Extratos Vegetais/farmacologia , Rutina/farmacologia , Animais , Neoplasias Hepáticas Experimentais/enzimologia , RatosRESUMO
Chronic lead exposure irreversibly damages the kidneys and may be associated with hypertension and renal insufficiency at sub-clinically toxic levels. Zinc supplementation reduces lead absorption and tissue retention in rodent models but the mechanisms are unknown. Metallothionein (MT) may function in lead detoxification. Our objective was to investigate the effects of marginal zinc (MZ) and supplemental zinc (SZ) intakes on renal lead and zinc accumulation, renal MT immunolocalization and levels. Weanling Sprague Dawley rats were assigned to MZ (8 mg Zn/kg diet), zinc-adequate control (CT; 30 mg Zn/kg), zinc-adequate diet-restricted (DR; 30 mg Zn/kg) or SZ (300 mg Zn/kg) groups, with and without lead acetate-containing drinking water (200 mg Pb/L) for 3 weeks. Kidneys were analyzed for lead and zinc by inductively coupled plasma spectroscopy and MT by immunolocalization and Western blotting. MZ had higher renal lead and lower renal zinc concentrations than CT. SZ was more protective than CT against renal lead accumulation. Renal MT levels reflected dietary intake (SZ > or = DR > or = CT > or = MZ) but lead had no effect on MT staining intensity, distribution, or relative protein amounts. In summary, while SZ lowered renal lead concentration, MT did not appear to function in renal lead accumulation. Future studies should explore alternate mechanisms of renal lead detoxification.