RESUMEN
(1) This investigation studied the effects of dietary saturated and polyunsaturated fatty acids (PUFAs) from the n-3 and n-6 series on insulin action and glucose uptake in broiler chickens. (2) One-day-old male chicks were fed on a commercial starter diet for 3 weeks, randomly divided into three groups (n = 6) and fed ad libitum on isonitrogenous experimental diets of equal energy density for a further 6 weeks. The diets contained 20.8 g/100 g protein and 80 g/kg of either edible tallow, fish oil or sunflower oil, giving diets high in saturated fatty acids, n-S PUFAs or n-6 PUFAs, respectively. (3) Jugular catheterisation was performed under general anaesthesia during week 4 of the dietary treatments and the birds given 7 d post-surgery to recover. To estimate insulin action, a bolus glucose infusion (1 g/kg) was given to each chicken and sequential blood samples taken over a one-hour period. To estimate the disappearance rate of glucose from the plasma and its incorporation into tissues, 2-deoxy-D-3H glucose (2DG-3H glucose) was infused into each chicken (50 microCi) 2 d later. (4) Although there were no significant differences in glucose clearance rate following the glucose infusion, the maximal insulin release in response to the glucose infusion was higher in the tallow group than in either the n-3 or n-6 PUFA dietary groups. There were no significant differences in the clearance rate of 2DG-3H glucose. Labelled glucose incorporation into the breast muscle was greater in birds given fish oil than in birds given tallow and significantly greater than in birds given sunflower oil. (5) The data suggest that the type of dietary fat can influence glucose metabolism and that this change in glucose utilisation may alter the energy metabolism of the broiler.
Asunto(s)
Pollos/metabolismo , Grasas de la Dieta/farmacología , Ácidos Grasos Omega-3/farmacología , Ácidos Grasos Omega-6/farmacología , Glucosa/metabolismo , Alimentación Animal , Animales , Grasas Insaturadas en la Dieta/farmacología , Insulina/metabolismo , MasculinoRESUMEN
Lipids play varied and critical roles in metabolism, with function dramatically modulated by the individual fatty acid moities in complex lipid entities. In particular, the fatty acid composition of membrane lipids greatly influences membrane function. Here we consider the role of dietary fatty acid profile on membrane composition and, in turn, its impact on prevalent disease clusters of the metabolic syndrome and mental illness. Applying the classical physiological conformer-regulator paradigm to quantify the influence of dietary fats on membrane lipid composition (i.e. where the membrane variable is plotted against the same variable in the environment--in this case dietary fats), membrane lipid composition appears as a predominantly regulated parameter. Membranes remain relatively constant in their saturated (SFA) and monounsaturated (MUFA) fatty acid levels over a wide range of dietary variation for these fatty acids. Membrane composition was found to be more responsive to n-6 and n-3 polyunsaturated fatty acid (PUFA) levels in the diet and most sensitive to n-3 PUFA and to the n-3/n-6 ratio. These differential responses are probably due to the fact that both n-6 and n-3 PUFA classes cannot be synthesised de novo by higher animals. Diet-induced modifications in membrane lipid composition are associated with changes in the rates of membrane-linked cellular processes that are major contributors to energy metabolism. For example, in the intrinsic activity of fundamental processes such as the Na+/K+ pump and proton pump-leak cycle. Equally, dietary lipid profile impacts substantially on diseases of the metabolic syndrome with evidence accruing for changes in metabolic rate and neuropeptide regulation (thus influencing both sides of the energy balance equation), in second messenger generation and in gene expression influencing a range of glucose and lipid handling pathways. Finally, there is a growing literature relating changes in dietary fatty acid profile to many aspects of mental health. The understanding of dietary lipid profile and its influence on membrane function in relation to metabolic dysregulation has exciting potential for the prevention and treatment of a range of prevalent disease states.
Asunto(s)
Dieta , Grasas de la Dieta/metabolismo , Ácidos Grasos/análisis , Lípidos de la Membrana/química , Lípidos de la Membrana/metabolismo , Animales , Grasas de la Dieta/administración & dosificación , Grasas de la Dieta/análisis , Grasas Insaturadas en la Dieta/administración & dosificación , Grasas Insaturadas en la Dieta/análisis , Grasas Insaturadas en la Dieta/metabolismo , Metabolismo Energético/fisiología , Ácidos Grasos Monoinsaturados/administración & dosificación , Ácidos Grasos Monoinsaturados/análisis , Ácidos Grasos Insaturados/administración & dosificación , Ácidos Grasos Insaturados/análisis , Humanos , Trastornos Mentales/metabolismo , Trastornos Mentales/fisiopatología , Síndrome Metabólico/metabolismo , Síndrome Metabólico/fisiopatologíaRESUMEN
The influence of membrane lipid composition on the molecular activity of a major membrane protein (the sodium pump) was examined as a test of the membrane pacemaker theory of metabolism. Microsomal membranes from the kidneys of cattle (Bos taurus) and crocodiles (Crocodylus porosus) were found to possess similar sodium pump concentrations, but cattle membranes showed a four- to fivefold higher enzyme (Na(+)-K(+)-ATPase) activity when measured at 37 degrees C. The molecular activity of the sodium pumps (ATP/min) from both species was fully recoverable when delipidated pumps were reconstituted with membrane from the original source (same species). The results of experiments involving species membrane crossovers showed cattle sodium pump molecular activity to progressively decrease from 3,245 to 1,953 (P < 0.005) to 1,031 (P < 0.003) ATP/min when subjected to two cycles of delipidation and reconstitution with crocodile membrane as a lipid source. In contrast, the molecular activity of crocodile sodium pumps progressively increased from 729 to 908 (P < 0.01) to 1,476 (P = 0.01) ATP/min when subjected to two cycles of delipidation and reconstitution with cattle membrane as a lipid source. The lipid composition of the two membrane preparations showed similar levels of saturated ( approximately 31-34%) and monounsaturated ( approximately 23-25%) fatty acids. Cattle membrane had fourfold more n-3 polyunsaturated fatty acids (11.2 vs. 2.9%) but had a reduced n-6 polyunsaturate content (29 vs. 43%). The results support the membrane pacemaker theory of metabolism and suggest membrane lipids and their polyunsaturates play a significant role in determining the molecular activity of the sodium pump.
Asunto(s)
Caimanes y Cocodrilos/metabolismo , Bovinos/metabolismo , Lípidos de la Membrana/metabolismo , Modelos Biológicos , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Animales , Ácidos Grasos Omega-3/metabolismo , Ácidos Grasos Omega-6/metabolismo , Membranas Intracelulares/metabolismo , Riñón/metabolismo , Microsomas/metabolismoRESUMEN
The effects of dietary saturated and polyunsaturated fatty acids (PUFAs) of the n-3 and n-6 series on avian pituitary sensitivity were investigated by infusing human growth hormone (GH) releasing hormone--fragment 1-29--and chicken luteinising hormone releasing hormone (LHRH) into catheterized broiler chickens. At 3 weeks of age three groups (n = 18; six birds per group) were fed for 6 weeks isonitrogenous and isoenergetic experimental diets containing 80 g/kg of edible tallow (saturated fatty acids), fish oil (n-3 PUFAs) or sunflower oil (n-6 PUFAs). Jugular catheterisation was performed under general anaesthesia during week four of the dietary treatments and the birds allowed 7 days post surgery to recover. A bolus of LHRH (20 microg/bird) and a GH releasing hormone (12.5 microg/kg) infusion was given on different days to each chicken and serial blood samples taken over a 1 h period. Plasma luteinising hormone and GH concentrations were measured by radioimmunoassay. Pre-infusion GH concentrations were similar for the tallow, fish and sunflower oil dietary groups (5.2 +/- 3.9, 5.2 +/- 1.0 and 6.1 +/- 3.1 ng/ml, respectively), however, GH concentration in response to the GH releasing hormone infusion was elevated in the sunflower oil group (44.7 +/- 5.7 ng/ml) when compared to chicken fed tallow (33.7 +/- 9.7ng/ml) or fish oil (21.3 +/- 5.0 ng/ml). There was a significant decrease (P < 0.05) in the clearance rate of plasma GH for the birds fed the fish oil compared with those fed sunflower oil with an intermediate value being observed in the tallow fed group. Pre-infusion plasma luteinising hormone concentrations for the birds fed tallow (3.2 +/- 0.7 ng/ml) were significantly elevated (P < 0.05) when compared to birds fed either the sunflower oil (0.84 +/- 0.25 ng.ml) or fish oil (0.93 +/- 0.22 ng/ml) diets. There were no significant differences between the dietary groups in either the maximal plasma luteinising concentration or its disappearance rate following the LHRH infusion. The data demonstrate that dietary fatty acids alter avian pituitary sensitivity and this modulation is determined by the nature of the dietary fat rather than the degree of saturation per se. In addition, this study also shows that dietary fats have a differential effect on pituitary cell activity and are specific to certain pituitary cell types.
Asunto(s)
Pollos , Grasas de la Dieta/administración & dosificación , Ácidos Grasos Omega-3/administración & dosificación , Ácidos Grasos Omega-6/administración & dosificación , Hipófisis/efectos de los fármacos , Animales , Grasas , Aceites de Pescado , Hormona Liberadora de Gonadotropina/administración & dosificación , Hormona del Crecimiento/sangre , Cinética , Hormona Luteinizante/sangre , Masculino , Tasa de Depuración Metabólica , Hipófisis/fisiología , Aceites de Plantas , Sermorelina/administración & dosificación , Aceite de GirasolRESUMEN
OBJECTIVES: To assess the accuracy of reporting from both a diet history and food record and identify some of the characteristics of more accurate reporters in a group of healthy adult volunteers for an energy balance study. DESIGN: Prospective measurements in free-living people. SETTING: Wollongong, Australia. SUBJECTS: Fifteen healthy volunteers (seven male, eight female; aged 22-59 y; body mass index (BMI) 19-33 kg/m(2)) from the local community in the city of Wollongong, Australia. INTERVENTIONS: Measurement of energy intake via diet history interview and 7 day food records, total energy expenditure by the doubly labelled water technique over 14 days, physical activity by questionnaire, and body fat by dual-energy X-ray absorptiometry. RESULTS: Increased misreporting of energy intake was associated with increased energy expenditure (r=0.90, P<0.0001, diet history; r(S)=0.79, P=0.0005, food records) but was not associated with age, sex, BMI or body fat. Range in number of recorded dinner foods correlated positively with energy expenditure (r(S)=0.63, P=0.01) and degree of misreporting (r(S)=0.71, P=0.003, diet history; r(S)=0.63, P=0.01, food records). Variation in energy intake at dinner and over the whole day identified by the food records correlated positively with energy expenditure (r=0.58, P=0.02) and misreporting on the diet history (r=0.62, P=0.01). CONCLUSIONS: Subjects who are highly active or who have variable dietary and exercise behaviour may be less accurate in reporting dietary intake. Our findings indicate that it may be necessary to screen for these characteristics in studies where accuracy of reporting at an individual level is critical.
Asunto(s)
Registros de Dieta , Metabolismo Energético/fisiología , Adulto , Australia , Composición Corporal/fisiología , Ingestión de Energía/fisiología , Conducta Alimentaria/fisiología , Femenino , Humanos , Entrevistas como Asunto , Estilo de Vida , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Valores de Referencia , Reproducibilidad de los Resultados , Factores de TiempoRESUMEN
OBJECTIVE: While the exact regulatory interactions between blood pressure (BP) and obesity are not completely understood, weight loss provides an alternative to pharmacological treatment of hypertension. The intent of this repeated measures study of mild-moderate hypertensive, moderately obese subjects (34 females/18 males) was to determine if the reduction in BP following weight loss could be further affected by modifying the fatty acid (FA) composition of the hypocaloric diet. METHODS: BP, insulin sensitivity (Si), and lipid parameters were assessed before and after a 10-week calorie-restricted period. Subjects were randomized to one of three dietary groups differing in FA composition. Reduced body weight was maintained for a further 4 weeks and body composition assessment, BP and heart rate measurements were repeated. RESULTS: Weight loss (10%) in obese hypertensive subjects resulted in substantial improvements in BP, Si and lipid profile. There was no additional effect on the reduction in BP by the type of FA consumed in the diet. Following weight loss, there was a trend for omega-3 FAs to have a protective effect on fat-free mass loss (compared to omega-6 FA Group and saturated FA Group) and a trend to further enhance Si. There were significant improvements in circulating lipid profiles independent of the dietary FA intervention following the weight loss. The improvements in BP and body composition were maintained during the weight-loss maintenance period. The type of fat consumed had minor differential effects on some of the measured metabolic outcomes. CONCLUSION: These results provide strong support for modest weight loss as a treatment for hypertension.
Asunto(s)
Grasas de la Dieta/farmacología , Ácidos Grasos Insaturados/farmacología , Hipertensión/etiología , Obesidad/complicaciones , Obesidad/metabolismo , Pérdida de Peso , Aldosterona/sangre , Presión Sanguínea/efectos de los fármacos , Composición Corporal/efectos de los fármacos , Ácidos Grasos/farmacología , Ácidos Grasos Omega-3/farmacología , Ácidos Grasos Omega-6 , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Hipertensión/fisiopatología , Insulina/fisiología , Lípidos/sangre , Masculino , Persona de Mediana Edad , Obesidad/sangre , Obesidad/patología , Renina/sangre , Pérdida de Peso/efectos de los fármacosAsunto(s)
Enfermedades Cardiovasculares/prevención & control , Dieta , Ejercicio Físico/fisiología , Resistencia a la Insulina , Animales , Enfermedades Cardiovasculares/etiología , Modelos Animales de Enfermedad , Predisposición Genética a la Enfermedad , Humanos , Insulina/sangre , Resistencia a la Insulina/genética , Obesidad/complicaciones , Obesidad/metabolismo , Obesidad/fisiopatologíaRESUMEN
This study investigated if prior eccentric contractions, and thus mechanical strain and muscle damage, exert an effect on the muscle membrane phospholipid fatty acid composition in rats, and whether a possible effect could be attenuated by dietary supplements. Twenty-three rats were randomised to three groups who received chow with added fish oil (n = 8), vitamin C (n = 8) or no supplement (n = 7). After 3 weeks of feeding, calf muscles on one side were stimulated electrically during anaesthesia causing eccentric contractions. Two days later the white gastrocnemius, a part of the stimulated calf muscle, was excised from both legs. In the muscles stimulated to contract eccentrically, compared to the control muscles, the proportion of arachidonic acid, C20:4,n-6 (17.7 +/- 0.6; 16.4 +/- 0.4% of total fatty acids, respectively) and docosapentanoeic acid, C22:5,n-3 (2.9 +/- 0.1 and 2.7 +/- 0.1% of total fatty acids, respectively) was uniformly higher across groups (P < 0.02) with no differences between diet groups. The proportion of long chain polyunsaturates was also significantly higher in the eccentrically contracted (39.9 +/- 0.6% of total fatty acids) compared to the control leg (38.2 +/- 0.6% of total fatty acids; P < 0.01). In contrast no differences were observed in the fatty acid composition of the triacylglycerols stored within the muscle. Thus one severe bout of eccentric contractions modulates the fatty acid composition of the muscle membrane phospholipids when compared to a control leg, and supplemental intake of fish oil or vitamin C did not attenuate this effect.
Asunto(s)
Ácidos Grasos/metabolismo , Contracción Muscular/fisiología , Músculo Esquelético/metabolismo , Fosfolípidos/metabolismo , Triglicéridos/metabolismo , Animales , Antioxidantes/administración & dosificación , Antioxidantes/farmacología , Ácido Ascórbico/administración & dosificación , Ácido Ascórbico/farmacología , Glucemia , Grasas de la Dieta/administración & dosificación , Estimulación Eléctrica , Aceites de Pescado/administración & dosificación , Aceites de Pescado/farmacología , Ácido Láctico/sangre , Masculino , Músculo Esquelético/citología , Músculo Esquelético/efectos de los fármacos , Distribución Aleatoria , Ratas , Ratas Wistar , Estrés MecánicoRESUMEN
Muscle metabolism was investigated in seven men during two 35 min cycling trials at 60% peak oxygen uptake, at 35 degrees C and 50% relative humidity. On one occasion, exercise was preceded by whole-body cooling achieved by immersion in water during a reduction in temperature from 29 to 24 degrees C, and, for the other trial, by immersion in water at a thermoneutral temperature (control, 34.8 degrees C). Pre-cooling did not alter oxygen uptake during exercise (P > 0.05), whilst the change in cardiac frequency and body mass both tended to be lower following pre-cooling (0.05 < P < 0.10). When averaged over the exercise period, muscle and oesophageal temperatures after pre-cooling were reduced by 1.5 and 0.6 degrees C respectively, compared with control (P < 0.05). Pre-cooling had a limited effect on muscle metabolism, with no differences between the two conditions in muscle glycogen, triglyceride, adenosine triphosphate, creatine phosphate, creatine or lactate contents at rest, or following exercise. These data indicate that whole-body pre-cooling does not alter muscle metabolism during submaximal exercise in the heat. It is more likely that thermoregulatory and cardiovascular strain are reduced, through lower muscle and core temperatures.
Asunto(s)
Regulación de la Temperatura Corporal/fisiología , Frío , Metabolismo Energético/fisiología , Músculo Esquelético/metabolismo , Esfuerzo Físico/fisiología , Adulto , Ciclismo/fisiología , Glucógeno/metabolismo , Humanos , Masculino , Triglicéridos/metabolismoRESUMEN
AIMS/HYPOTHESIS: The amount and quality of fat in the diet could be of importance for development of insulin resistance and related metabolic disorders. Our aim was to determine whether a change in dietary fat quality alone could alter insulin action in humans. METHODS: The KANWU study included 162 healthy subjects chosen at random to receive a controlled, isoenergetic diet for 3 months containing either a high proportion of saturated (SAFA diet) or monounsaturated (MUFA diet) fatty acids. Within each group there was a second assignment at random to supplements with fish oil (3.6 g n-3 fatty acids/d) or placebo. RESULTS: Insulin sensitivity was significantly impaired on the saturated fatty acid diet (-10%, p = 0.03) but did not change on the monounsaturated fatty acid diet (+2%, NS) (p = 0.05 for difference between diets). Insulin secretion was not affected. The addition of n-3 fatty acids influenced neither insulin sensitivity nor insulin secretion. The favourable effects of substituting a monounsaturated fatty acid diet for a saturated fatty acid diet on insulin sensitivity were only seen at a total fat intake below median (37E%). Here, insulin sensitivity was 12.5% lower and 8.8% higher on the saturated fatty acid diet and monounsaturated fatty acid diet respectively (p = 0.03). Low density lipoprotein cholesterol (LDL) increased on the saturated fatty acid diet (+4.1%, p < 0.01) but decreased on the monounsaturated fatty acid diet (MUFA) (-5.2, p < 0.001), whereas lipoprotein (a) [Lp(a)] increased on a monounsaturated fatty acid diet by 12% (p < 0.001). CONCLUSIONS/INTERPRETATION: A change of the proportions of dietary fatty acids, decreasing saturated fatty acid and increasing monounsaturated fatty acid, improves insulin sensitivity but has no effect on insulin secretion. A beneficial impact of the fat quality on insulin sensitivity is not seen in individuals with a high fat intake (> 37E%).
Asunto(s)
Glucemia/metabolismo , Grasas Insaturadas en la Dieta/farmacología , Grasas de la Dieta/farmacología , Ácidos Grasos Monoinsaturados/farmacología , Insulina/sangre , Insulina/metabolismo , Fosfolípidos/sangre , Adulto , Anciano , Apolipoproteína A-I/sangre , Apolipoproteínas B/sangre , Glucemia/efectos de los fármacos , Colesterol/sangre , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Ácidos Grasos Omega-3/farmacología , Femenino , Aceites de Pescado/farmacología , Prueba de Tolerancia a la Glucosa , Humanos , Secreción de Insulina , Lipoproteína(a)/sangre , Masculino , Persona de Mediana Edad , Fosfolípidos/química , Valores de Referencia , Triglicéridos/sangreRESUMEN
Training improves insulin sensitivity, which in turn may affect performance by modulation of fuel availability. Insulin action, in turn, has been linked to specific patterns of muscle structural lipids in skeletal muscle. This study investigated whether regular exercise training exerts an effect on the muscle membrane phospholipid fatty acid composition in humans. Seven male subjects performed endurance training of the knee extensors of one leg for 4 wk. The other leg served as a control. Before, after 4 days, and after 4 wk, muscle biopsies were obtained from the vastus lateralis. After 4 wk, the phospholipid fatty acid contents of oleic acid 18:1(n-9) and docosahexaenoic acid 22:6(n-3) were significantly higher in the trained (10.9 +/- 0.5% and 3.2 +/- 0.4% of total fatty acids, respectively) than the untrained leg (8.8 +/- 0.5% and 2.6 +/- 0.4%, P < 0.05). The ratio between n-6 and n-3 fatty acids was significantly lower in the trained (11.1 +/- 0.9) than the untrained leg (13.1 +/- 1.2, P < 0.05). In contrast, training did not affect muscle triacylglycerol fatty acid composition. Citrate synthase activity was increased by 17% in the trained compared with the untrained leg (P < 0.05). In this model, diet plays a minimal role, as the influence of dietary intake is similar on both legs. Regular exercise training per se influences the phospholipid fatty acid composition of muscle membranes but has no effect on the composition of fatty acids stored in triacylglycerols within the muscle.
Asunto(s)
Ácidos Grasos/análisis , Músculo Esquelético/metabolismo , Fosfolípidos/química , Resistencia Física , Adulto , Ácidos Docosahexaenoicos/análisis , Ingestión de Energía , Prueba de Esfuerzo , Ácidos Grasos Insaturados/análisis , Humanos , Masculino , Músculo Esquelético/enzimología , Ácidos Oléicos/análisis , Triglicéridos/químicaAsunto(s)
Grasas de la Dieta/administración & dosificación , Grasas de la Dieta/clasificación , Obesidad , Tejido Adiposo/metabolismo , Membrana Celular/metabolismo , Metabolismo Energético , Ácidos Grasos Insaturados/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Neuropéptidos/genéticaRESUMEN
The activity of the ubiquitous Na(+)/K(+)-ATPase represents a substantial portion of the resting metabolic activity of cells, and the molecular activity of this enzyme from tissues of different vertebrates can vary several-fold. Microsomes were prepared from the kidney and brain of the rat (Rattus norvegicus) and the cane toad (Bufo marinus), and Na(+)/K(+)-ATPase molecular activity was determined. The membrane lipids surrounding this enzyme were isolated and phospholipids prepared. 'Surface pressure/area' isotherms were measured in monolayers for both membrane lipids and phospholipids using classic Langmuir trough techniques. Microsomal lipid composition was also measured. Whilst significant correlations were observed between membrane composition and Na(+)/K(+)-ATPase molecular activity, the strongest correlations were found between the molecular activity and parameters describing the packing of the surrounding membrane lipids and phospholipids. The influence of membrane lipid composition, especially membrane acyl composition, on the activity of a membrane protein mediated by physical properties of the lipids may represent a fundamental principle applicable to other membrane proteins.
Asunto(s)
Lípidos de la Membrana/análisis , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Animales , Encéfalo/ultraestructura , Bufo marinus , Ácidos Grasos/análisis , Riñón/ultraestructura , Cinética , Microsomas/química , Microsomas/enzimología , Fosfolípidos/análisis , Ratas , ATPasa Intercambiadora de Sodio-Potasio/análisis , Especificidad de la EspecieRESUMEN
A high fat diet leads to progressive development of obesity and leptin resistance in C57 mice with a middle stage of peripheral, but not central, leptin resistance. This stage is characterized by increased fat accumulation despite relative hypophagia. At a later stage central leptin resistance ensues along with hyperphagia, rapid weight and fat gain. The aim of this study is to characterize the mRNA levels of leptin receptor (LR), neuropeptide Y (NPY) and pro-opiomelanocortin (POMC) in high fat (HFF) and low fat (LFF) fed groups of mice. The hypothalamic arcuate nucleus (Arc) was investigated, as was the choroid plexus (ChP) in the case of the leptin receptor. No differences between groups were seen in LR, NPY or POMC mRNA levels after 1 week of feeding. After 8 and 19 weeks, the HFF mice, compared to LFF controls, demonstrated a +45% (P<0. 003) and +84% (P<0.0001) increase in the ratio of visceral fat to body weight and +223% (P<0.0001) and +468% (P<0.0001) elevation in plasma leptin levels, respectively. At 8 weeks, LR mRNA expression showed a +98% (P<0.016) and +66% (P<0.0001) increase in ChP and Arc, respectively, while Arc NPY mRNA showed down-regulation by -45% (P<0. 006). Arc POMC mRNA showed no significant changes between groups at 8 weeks. However, after long-term (19 weeks) feeding, the HFF mice displayed significantly -26% (P<0.039) and -33% (P<0.0015) reduced LR mRNA in the ChP and Arc, respectively, with Arc POMC and NPY mRNAs down by -55% (P<0.004) and -32% (P<0.009), respectively. The present results suggest that in the middle stage of development of high fat-induced obesity, when central leptin sensitivity is maintained, the increased leptin receptor expression may play a role to defend against obesity which is overwhelmed as central leptin insensitivity develops. In this later stage the down-regulation of the POMC system may be important in the final breakdown of weight homeostasis.
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Encéfalo/metabolismo , Proteínas Portadoras/genética , Neuropéptido Y/genética , Obesidad/metabolismo , Proopiomelanocortina/genética , ARN Mensajero/metabolismo , Receptores de Superficie Celular , Tejido Adiposo/patología , Animales , Grasas de la Dieta/administración & dosificación , Ingestión de Energía , Epidídimo , Riñón , Leptina/sangre , Masculino , Ratones , Ratones Endogámicos C57BL , Obesidad/etiología , Obesidad/patología , Receptores de LeptinaRESUMEN
Insulin resistance and hyperinsulinaemia are associated with hypertension although a causative relationship has not been established. The aim of this study was to determine whether a short term reduction in insulin sensitivity induced by nicotinic acid treatment (NA) would alter blood pressure. The study was a double-blind randomised placebo-controlled cross-over study. Seven healthy volunteers, three males and four females were randomised to placebo or NA 500 mg daily for 7 days then 1 g daily for a further 7 days. Hyperinsulinaemic euglycaemic clamp, indirect calorimetry, 24-h ambulatory blood pressure monitoring (ABPM) and forearm blood flow measurement (FABF) were performed at day 14 of each treatment phase. NA significantly reduced the glucose infusion rate required to maintain euglycaemia in all subjects (placebo vs NA; 31.5+/-4.2 vs. 26.2+/-4.6 micromol/kg/min, P = 0.002) associated with a decrease in non-oxidative glucose disposal. NA did not significantly alter 24-h mean systolic or diastolic blood pressure. Fasting glucose, insulin and non-esterified free fatty acid (NEFA) levels remained unchanged, energy expenditure and substrate oxidation were not altered by NA. These results suggest a short term reduction in insulin sensitivity with NA is not accompanied by a change in blood pressure. This may relate to the short duration of treatment, to a dissociation between insulin resistance and hypertension or to other homeostatic mechanisms which prevent blood pressure rising in subjects not predisposed to hypertension.
Asunto(s)
Presión Sanguínea/efectos de los fármacos , Resistencia a la Insulina/fisiología , Niacina/farmacología , Adulto , Glucemia/análisis , Monitoreo Ambulatorio de la Presión Arterial , Estudios Cruzados , Método Doble Ciego , Metabolismo Energético/efectos de los fármacos , Ayuno/sangre , Ácidos Grasos no Esterificados/sangre , Femenino , Técnica de Clampeo de la Glucosa , Humanos , Masculino , Oxidación-Reducción/efectos de los fármacos , Valores de ReferenciaRESUMEN
AIMS/HYPOTHESIS: Fat balance is critical in the aetiology of obesity and related diseases. Lipoprotein lipase is of major importance in lipid metabolism. The aim of this study was to investigate the long-term effects of the lipoprotein lipase activator, NO-1886, on substrate utilisation, adiposity and insulin action in rats fed a high-fat diet. METHODS: Male, Sprague-Dawley rats were fed for 10 weeks on a chow diet or a high-fat diet with, or without, NO-1886 (50 mg x kg(-1) x day(-1)). Weight gain, fat accumulation and both hormone-sensitive and lipoprotein, lipase activities were measured. Insulin action was assessed by the euglycaemic hyperinsulinaemic clamp and metabolic rate/substrate utilisation by open-circuit respirometry. RESULTS: Compared with chow-fed controls, a high-fat diet increased weight gain, an effect lessened by NO-1886 [weight gain (g): chow, 37 +/- 3, high-fat, 222 +/- 9; high-fat + NO-1886, 109 +/- 6, all groups differed p < 0.001]. A similar pattern existed for fat accumulation [visceral fat (g): chow, 35.9 +/- 3.2; high-fat, 81.9 +/- 6.6; high-fat + NO-1886, 52.3 +/- 4.7, p < 0.01 high-fat vs the other groups]. A high-fat diet induced wholebody insulin resistance (clamp glucose infusion rate: 4.8 +/- 1.3 mg x kg(-1) x min(-1) vs 10.6 +/- 1.1 for the chow group, p < 0.01) with NO-1886 lessening this effect (8.3 +/- 0.5, p < 0.05 vs high-fat). The 24-h respiratory quotient was lower in the high-fat + NO-1886 group (0.825 +/- 0.010) compared with high-fat alone (0.849 +/- 0.004, p < 0.05). A high-fat diet increased lipoprotein and hormone-sensitive, lipase activities in epididymal fat, an effect not altered by NO-1886. In myocardium and skeletal muscle a high-fat diet lowered lipoprotein lipase activity, an effect lessened by NO-1886. CONCLUSION/INTERPRETATION: Lipoprotein lipase activators could have potential benefits for the treatment of obesity by increasing fat utilisation.
Asunto(s)
Tejido Adiposo/enzimología , Benzamidas/farmacología , Grasas de la Dieta , Hipolipemiantes/farmacología , Resistencia a la Insulina/fisiología , Lipoproteína Lipasa/metabolismo , Compuestos Organofosforados/farmacología , Animales , Glucemia/metabolismo , Activación Enzimática , Ácidos Grasos no Esterificados/sangre , Técnica de Clampeo de la Glucosa , Hiperinsulinismo , Infusiones Intravenosas , Insulina/administración & dosificación , Insulina/sangre , Insulina/farmacología , Masculino , Miocardio/enzimología , Ratas , Ratas Sprague-Dawley , Triglicéridos/sangreRESUMEN
Critical insights into the etiology of insulin resistance have been gained by the use of animal models where insulin action has been modulated by strictly controlled dietary interventions not possible in human studies. Overall, the literature has moved from a focus on macronutrient proportions to understanding the unique effects of individual subtypes of fats, carbohydrates and proteins. Substantial evidence has now accumulated for a major role of dietary fat subtypes in insulin action. Intake of saturated fats is strongly linked to development of obesity and insulin resistance, while that of polyunsaturated fats (PUFAs) is not. This is consistent with observations that saturated fats are poorly oxidized for energy and thus readily stored, are poorly mobilized by lipolytic stimuli, impair membrane function, and increase the expression of genes associated with adipocyte profileration (making their own home). PUFAs have contrasting effects in each instance. It is therefore not surprising that increased PUFA intake in animal models is associated with improved insulin action and reduced adiposity. Less information is available for carbohydrate subtypes. Early work clearly demonstrated that diets high in simple sugars (in particular fructose) led to insulin resistance. However, again attention has rightly shifted to the very interesting issue of subtypes of complex carbohydrates. While no differences in insulin action have yet been shown, differences in substrate flux suggest there could be long-term beneficial effects on the fat balance of diets enhanced in slowly digested/resistant starches. A new area of major interest is in protein subtypes. Recent results have shown that rats fed high-fat diets where the protein component was from casein or soy were insulin-resistant, but when the protein source was from cod they were not. These are exciting times in our growing understanding of dietary factors and insulin action. While it has been clear for some time that 'oils ain't oils', the same is now proving true for carbohydrates and proteins.
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Grasas de la Dieta/efectos adversos , Resistencia a la Insulina , Obesidad/etiología , Animales , Carbohidratos de la Dieta/administración & dosificación , Grasas Insaturadas en la Dieta/administración & dosificación , Proteínas en la Dieta/administración & dosificación , Modelos Animales de Enfermedad , Aceites de Pescado/administración & dosificación , Humanos , Obesidad/dietoterapia , Aceites de Plantas/administración & dosificación , RatasRESUMEN
OBJECTIVE: To investigate relationships between dietary macronutrient intakes and glucose tolerance in pregnancy RESEARCH DESIGN AND METHODS: Nulliparous pregnant Chinese women diagnosed with gestational diabetes mellitus (GDM) (n = 56) were compared to age-, gestational age-, height-, and parity-matched groups with normal glucose tolerance (n = 77) and glucose intolerance (IGT) (n = 38) based on the results of an oral glucose tolerance test (National Diabetes Data Group criteria), performed between 24 and 28 weeks of pregnancy. A 24-h recall dietary assessment was also obtained at the time of screening. RESULTS: Subjects with IGT and GDM were significantly heavier (66.1 +/- 1.4 and 68.6 +/- 1.2 kg, respectively, mean +/- SEM) (P < 0.0001) than the normal group (61.2 +/- 1.8 kg) and had a higher BMI. Overall energy intake was similar between groups, as were the intakes of each macronutrient (%kcal). However, there was a highly significant reduction in polyunsaturated fat intake in the IGT and GDM groups whether expressed as %kcal, % of total fat, or fat kcal. This effect was independent of body weight or BMI whether assessed by ordinal logistic regression or by analysis of a weight- and BMI-matched subgroup of the subjects (P = 0.002 for %kcal; n = 47 normal, 26 IGT, and 43 GDM subjects). In logistic regression analysis of the complete data set, increased body weight (P < 0.0001) and decreased polyunsaturated fat intake (P = 0.0014) were both independent predictors of glucose intolerance (IGT and GDM), as were increased body weight and a low dietary polyunsaturated to saturated fat ratio. CONCLUSIONS: Increased polyunsaturated fat intake is associated with a reduced incidence of glucose intolerance during pregnancy. This finding may have major implications for dietary management of women with or at risk of developing GDM.
Asunto(s)
Glucemia/metabolismo , Diabetes Gestacional/sangre , Dieta , Intolerancia a la Glucosa/sangre , Embarazo/sangre , Adulto , Pueblo Asiatico , Índice de Masa Corporal , Peso Corporal , China , Grasas de la Dieta , Ingestión de Energía , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Segundo Trimestre del Embarazo , Valores de Referencia , Análisis de RegresiónRESUMEN
OBJECTIVE: This study examines the relationship between obesity and foot structure in prepubescent children. DESIGN: Field-based, experimental data on BMI (body mass index) and foot structure were collected for 431 consenting children from 18 randomly selected primary schools. SUBJECTS: Of the 431 participants, 62 obese (BMI>95th percentile) and 62 non-obese (10th percentile