RESUMEN
The results of this study indicate that aging is associated with progressive declines in the normal dietary and metabolic responses to diet and environment in this animal model. The normal thermic and hormonal responses to diet and environment are thought to contribute to the fine regulation of energy balance by modulation of the efficiency of energy utilization or storage [25]. In the obese phenotype, the declines in the above variables may be further complicated by the presence of long-standing insulin resistance, and by perturbations in the normal metabolism and action of thyroid hormones, particularly T3. These may further contribute, individually or in combination with other factors, to an enhancement of energy storage and thereby contribute to maintaining the obese state. Moreover, the effects of progressive increases in obesity further exacerbate the decline in the economy of energy utilization and storage. Thus the impact of these physiologic changes of aging and obesity may impart significant alterations on the efficiency of energy metabolism, which in turn may contribute to some of the pathophysiologic changes associated with longevity, and could influence nutritional indices in affected individuals. As nations become progressively more industrialized, the incidence of overweight conditions--including obesity, NIDDM, and related metabolic disorders--has been shown to become increased and, along with those changes, the metabolic and pathophysiologic sequelae related to those disorders become more common [6-8]. A greater understanding of mechanisms of impaired energy metabolism and energy balance in aging may provide new insight into the nutritional factors that may contribute to obesity in aging, their modulation, and the emergence of a longer, healthier lifestyle.
Asunto(s)
Envejecimiento/metabolismo , Modelos Animales de Enfermedad , Metabolismo Energético , Obesidad/fisiopatología , Animales , Regulación de la Temperatura Corporal/fisiología , Hiperlipidemias , Hiperfagia/etiología , Hiperfagia/metabolismo , Resistencia a la Insulina , Obesidad/metabolismo , RatasRESUMEN
The effects of norepinephrine and insulin on glucose transport were investigated in brown adipocytes isolated from obese nondiabetic Lister and Albany (LA/N-cp strain) rats (O-LA), obese diabetic spontaneously hypertensive (SHR/N-cp strain) rats (O-SHR), and from their lean (L) controls to test whether the decreased calorigenic response to norepinephrine of O-SHR adipocytes was specifically associated with alterations in glucose metabolism. Norepinephrine and insulin independently stimulated glucose transport in L-LA, O-LA, and L-SHR brown adipocytes, but their stimulatory effects were markedly reduced in O-SHR cells. Both insulin responsiveness and the total number of insulin receptors were significantly decreased in O-SHR adipocytes but not in O-LA cells. The number of high-affinity beta 1/beta 2-adrenoceptors was significantly increased (+70%) in O-LA adipocytes but was similar in L-SHR and O-SHR cells. These results indicate that 1) major metabolic defects are present in brown adipose tissue (BAT) of O-SHR but not of O-LA, although these two strains are homozygous for the cp allele, 2) postreceptor defects are predominantly involved in O-SHR adipocyte refractoriness to norepinephrine, and 3) a reduced mitochondrial content may represent the principal metabolic alteration explaining the decreased effects of norepinephrine on both thermogenesis and glucose transport. It is postulated that the marked insulin resistance of O-SHR leads to a decreased mitochondriogenesis in BAT, resulting in a diminished tissue thermogenic capacity and reduced glucose metabolism, thereby contributing to obesity and diabetes.
Asunto(s)
Tejido Adiposo Pardo/metabolismo , Diabetes Mellitus/metabolismo , Glucosa/metabolismo , Insulina/farmacología , Norepinefrina/farmacología , Obesidad/metabolismo , Tejido Adiposo Pardo/patología , Animales , Transporte Biológico/efectos de los fármacos , Diabetes Mellitus/patología , Resistencia a Medicamentos , Femenino , Hibridación Genética , Insulina/metabolismo , Resistencia a la Insulina , Consumo de Oxígeno/efectos de los fármacos , Propanolaminas/metabolismo , Ratas , Ratas Endogámicas SHR , Ratas MutantesRESUMEN
1. Groups of lean and obese-diabetic (NIDDM) congenic male SHR/Nutl parallel-cp rats were fed a nutritionally adequate, high carbohydrate diet ad libitum with or without the alpha-glucosidase inhibitor miglitol (150 mg/kg diet) from 8 until 15 weeks of age, and key glycemic parameters were monitored throughout the study. 2. Miglitol treatment resulted in clinical improvement toward normal in percent glycosylated hemoglobin, glycemic and insulinogenic responses to an oral glucose tolerance, and in liver glucokinase activity, in concert with modest decreases in weight gain in obese rats. 3. These observations are consistent with improved insulin sensitivity in peripheral tissues following miglitol treatment, and indicate that this drug may be a useful adjunct to diet in the treatment of obesity, NIDDM, and possibly other disorders of carbohydrate metabolism.
Asunto(s)
Glucemia/análisis , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus/sangre , Glucosamina/análogos & derivados , Inhibidores de Glicósido Hidrolasas , Obesidad , 1-Desoxinojirimicina/análogos & derivados , Animales , Peso Corporal/efectos de los fármacos , Ingestión de Alimentos/efectos de los fármacos , Glucosamina/farmacología , Iminopiranosas , Masculino , Ratas , Ratas Endogámicas SHRRESUMEN
1. To determine the effects of gene dilution on development of IGT, NIDDM and in vitro glucose oxidation, heterozygous lean LA/N-cp female and SHR/N-cp male rats were mated, and F1 offspring studied at periodic intervals to determine the prevalence of obese and diabetic traits. 2. Obesity occurred in 25% of offspring by 5 weeks of age, consistent with inheritance of the autosomal recessive cp trait. 3. IGT occurred in all obese male F1, 67% of obese female F1, and 18% of the lean male F1 rats by 5 months of age, and diabetes occurred in 80% of male obese and 17% of female obese rats from 6 months of age. Glycosuria occurred with glucose intolerance, and was more severe in rats with NIDDM than IGT. 4. Rates of in vitro glucose oxidation were greater in diaphragm and adipose tissue, and were greater in the presence of insulin (100 mu Units/ml) in obese female but not obese male F1 rats. 5. These results indicate that the development of glucose intolerance is more prominent in male than in female F1 rats, that the progression of IGT to NIDDM occurs later in life in the F1 hybrid than in the SHR/N-cp strain from which the diabetic trait was transmitted, and that genetic dilution of the diabetic trait via hybrid breeding results in a delay in the expression of NIDDM which is chronologically more similar to that which occurs in man.
Asunto(s)
Diabetes Mellitus Tipo 2/genética , Glucosa/metabolismo , Animales , Cruzamientos Genéticos , Diabetes Mellitus/genética , Diabetes Mellitus/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Femenino , Prueba de Tolerancia a la Glucosa , Heterocigoto , Cinética , Masculino , Obesidad , Tamaño de los Órganos , Oxidación-Reducción , Ratas , Ratas Endogámicas SHRRESUMEN
The experimental evidence supporting a direct role for hyperinsulinemia as a cause of insulin resistance remains equivocal. Amylin, an islet beta-cell peptide cosecreted with insulin in response to nutrient stimuli, causes insulin resistance when infused into intact animals or applied to isolated skeletal muscles. We compared measures of amylin and insulin gene expression between control and genetically obese, insulin-resistant Lister Albany/NIH-(LA/N-cp) rats. Pancreatic amylin messenger RNA levels were increased 7.8 +/- 0.7-fold (mean +/- SEM), and plasma amylin-like immunoreactive material was increased 10.9 +/- 1.1-fold (LA/N-lean, 14 +/- 4 pM; LA/N-cp, 153 +/- 16 pM; p less than 0.0001) in obese rats. Pancreatic insulin I mRNA levels were increased 7.4 +/- 0.5-fold, and plasma insulin levels 20.0 +/- 5.0-fold, in these rats (LA/N-lean, 308 +/- 84 pM; LA/N-cp 6,120 +/- 1,540 pM; p less than 0.0001). The EC50 for insulin-stimulated incorporation of glucose into glycogen was about fourfold higher in muscles isolated from obese rats. The present results, coupled with previous observations, support the hypothesis that hyperamylinemia, rather than hyperinsulinemia per se, could have directly caused the insulin resistance in the obese LA/N-cp rats. Hyperamylinemia needs to be considered in future experimental studies probing the relation between hyperinsulinemia and insulin resistance.
Asunto(s)
Amiloide/sangre , Hiperinsulinismo/sangre , Resistencia a la Insulina , Obesidad/genética , Amiloide/genética , Amiloide/metabolismo , Amiloide/fisiología , Animales , Glucemia/metabolismo , Prueba de Tolerancia a la Glucosa , Glucógeno/metabolismo , Hiperinsulinismo/complicaciones , Hiperinsulinismo/fisiopatología , Insulina/sangre , Polipéptido Amiloide de los Islotes Pancreáticos , Músculos/metabolismo , Obesidad/complicaciones , ARN Mensajero/metabolismo , Ratas , Ratas EndogámicasRESUMEN
We previously reported that the decreased sensitivity of brown adipose tissue (BAT) from obese Zucker rats to the calorigenic effects of norepinephrine is associated with a marked resistance to insulin, and we suggested that this defect may explain, at least in part, the increased energy gain efficiency of fa/fa rats. To test whether insulin resistance and/or diabetes leads to a reduced BAT thermogenesis in other genetic models of obesity, we compared BAT metabolic properties of obese Zucker rats with that of obese-nondiabetic LA/N-cp and obese-diabetic SHR/N-cp rats. It was found that the responsiveness and sensitivity of isolated brown adipocytes to the calorigenic effects of norepinephrine (10-100 mM) were markedly reduced in SHR/N-cp rats as compared to their lean controls (the Vmax was decreased by 3-4 times and the EC50 value was doubled). In the same cells, there was a similar decrease in the respiratory effects of dibutyryl cAMP (DBcAMP), revealing the presence of a major post-receptor defect. Remarkably, total cytochrome oxidase activity (an index of cell mitochondrial content) was also decreased by 3-4 times in SHR/N-cp rats, suggesting that a reduced BAT mitochondrial content is responsible for the defective thermogenesis. Similarly to Zucker rats, adipocytes isolated from SHR/N-cp rats were resistant to the metabolic effects of insulin (glucose transport and antithermogenesis). Cells from obese Zucker rats were also desensitized to the metabolic effects of norepinephrine and insulin but their thermogenic capacity was not reduced. In contrast, all the above parameters were normal in obese-nondiabetic LA/N-cp rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Tejido Adiposo Pardo/metabolismo , Regulación de la Temperatura Corporal , Diabetes Mellitus Experimental/metabolismo , Resistencia a la Insulina , Obesidad/metabolismo , Tejido Adiposo Pardo/efectos de los fármacos , Tejido Adiposo Pardo/enzimología , Animales , Transporte Biológico/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Complejo IV de Transporte de Electrones/análisis , Femenino , Glucosa/metabolismo , Insulina/farmacología , Mitocondrias/enzimología , Norepinefrina/farmacología , Consumo de Oxígeno/efectos de los fármacos , Ratas , Ratas Endogámicas SHR , Ratas ZuckerRESUMEN
Restriction of energy intake significantly reduces mammary tumorigenesis in normal rats exposed to carcinogens. Genetically obese LA/N-cp (corpulent) female rats were given 7,12-dimethylbenz[a]anthracene and fed purified diets ad libitum or restricted to 60% of the ad libitum caloric intake. Phenotypically lean littermates were also fed ad libitum. Obese animals developed large mammary tumors more rapidly than genetically normal rats so that 100% of the animals had tumors in less than 16 weeks. Only 21% of the lean animals developed tumors; the energy restricted obese animals had a tumor incidence of 27%. Although obese rats fed the restricted diet weighed significantly less than those fed ad libitum, percent body fat was not reduced, indicating that lean tissue was affected more. Obese animals were markedly hyperinsulinemic (1003 +/- 193 microunits/ml) and energy restriction reduced this to 328 +/- 41; the lean animals had insulin levels of 12 +/- 2. Tumor-bearing rats had higher insulin levels than rats without tumors. These data suggest that body fatness is not directly associated with risk of carcinogenesis. Lean body mass, adipose tissue mass, and their interaction with insulin in its capacity as a growth factor rather than body fatness per se may be determinants of tumor promotion.
Asunto(s)
Dieta Reductora , Neoplasias Mamarias Experimentales , Obesidad , 9,10-Dimetil-1,2-benzantraceno/efectos adversos , Animales , Glucemia/análisis , Composición Corporal , Peso Corporal , Colesterol/sangre , Femenino , Insulina/sangre , Ratas , Triglicéridos/sangreRESUMEN
1. Adipose mass and cellularity were studied in congenic female SHR/N-cp rats fed iosenergetic diets containing 54% carbohydrate as sucrose (SU) or cooked cornstarch (CS), 20% protein, 16% mixed dietary fat plus vitamins, minerals, and non-nutritive fiber ad libitum from 5 weeks until 8.5 months of age. Measures of adipocyte lipid content, cell number per depot, and mass of principal white (WAT) and interscapular brown (IBAT) adipoe tissue depots were determined at the end of the study. 2. Final body weights (BW) of corpulent rats were more than twice those for their lean littermates, and were greater when fed the SU than the CS diet in both phenotypes. Phenotype effects (corpulent greater than lean) were present for fat pad weight, adipocyte number, and adipocyte lipid content in the dorsal (DOR) and retroperitoneal (RP) WAT depots. Diet effects were present for depot weight, adipocyte number, and adipocyte lipid content in both WAT depots, and were of qualitatively similar magnitude in both phenotypes. 3. IBAT weights, IBAT:BW ratios, and IBAT cell number of corpulent greater than lean, and were greater than with SU than CS diet in both phenotypes. 4. These results indicate that obesity in the corpulent phenotype of the SHR/N-cp rat occurs as the result of hypertrophy and hyperplasia of white adipose tissue, and that isoenergetic substitution of simple for complex carbohydrate resulted in greater fat accretion in both phenotypes. The greater diet and phenotype-associated adiposity occurred despite greater mass and cellularity of BAT. The results also indicate that sexual dimorphism occurs regarding effects of diet and phenotype on expression of adipose tissue development in this strain.
Asunto(s)
Tejido Adiposo/patología , Carbohidratos de la Dieta/administración & dosificación , Obesidad/patología , Tejido Adiposo Pardo/patología , Animales , Femenino , Fenotipo , Ratas , Ratas Endogámicas SHRRESUMEN
1. Groups of lean, obese, and obese-non-insulin-dependent diabetic LA/N-cp and SHR/N-cp rats were administered the a-glucosidase inhibitor Miglitol (150 mg/kg diet, ad libitum) from 8 until 15 weeks of age. 2. Phenotype effects (obese greater than lean) were present for weight gain, adiposity, serum glycemic and lipid parameters, and for liver glucokinase, glucose-6-phosphate dehydrogenase, and malic enzyme activity. Miglitol treatment was associated with improvements in glucokinase and malic enzyme in both strains, and in improvements in glycemic parameters in obese rats. 3. These results are consistent with variable improvements in glycemic control and insulin action following low dose Miglitol treatment, and indicate that indirect effects of the drug on insulin sensitivity in peripheral tissues and on glucoregulatory enzymes may contribute to the glycemic improvements observed with this drug, while greater dosages or longer treatment may be required to observe comparable improvements in adiposity or plasma lipid profiles.
Asunto(s)
Diabetes Mellitus/metabolismo , Glucosamina/análogos & derivados , Inhibidores de Glicósido Hidrolasas , Lípidos/sangre , Hígado/enzimología , Obesidad/metabolismo , 1-Desoxinojirimicina/análogos & derivados , Tejido Adiposo/patología , Animales , Glucemia/metabolismo , Proteínas Sanguíneas/metabolismo , Diabetes Mellitus/patología , Glucoquinasa/metabolismo , Glucosamina/farmacología , Glucosafosfato Deshidrogenasa/metabolismo , Iminopiranosas , Insulina/sangre , Hígado/efectos de los fármacos , Obesidad/patología , Fenotipo , Ratas , Aumento de Peso/efectos de los fármacosRESUMEN
1. Groups of congenic adult male lean and obese LA/N-cp rats were fed stock chow or the chow diet plus a cafeteria diet supplement from 4 until 6 months of age. 2. Weight gain, adipose cellularity, and adiposity were greater in obese than in lean rats and all three parameters increased more rapidly in obese than in lean rats when fed the cafeteria-supplemented diet. 3. Resting metabolic rates and basal urinary vanilylmandelic acid excretion were greater in lean than in obese rats, while serum triiodothyronine concentrations were similar in both phenotypes. The cafeteria diet was associated with significant increases in all three metabolic parameters in lean but not in obese rats. 4. The results of this study indicate that the obese phenotype of this strain has an impaired capacity for non-shivering thermogenesis (NST), in association with an enhanced propensity for development of obesity when fed stock or cafeteria diets. Moreover, the impairment in NST involves both sympathetic and thyroidal components, and is likely to be contributory if not causative of obesity in this strain.
Asunto(s)
Regulación de la Temperatura Corporal/fisiología , Dieta/efectos adversos , Obesidad/etiología , Tejido Adiposo/patología , Tejido Adiposo Pardo/patología , Animales , Metabolismo Basal , Masculino , Obesidad/patología , Obesidad/fisiopatología , Tamaño de los Órganos , Ratas , Ratas Mutantes , Aumento de PesoRESUMEN
1. Groups of lean and obese male SHR/N-cp rats were fed isoenergetic diets containing 54% carbohydrate as cornstarch (CS) or sucrose (SU) plus other nutrients from 5 weeks of age, and measures of adiposity, thyroxine 5' deiodinase (T4-5'DI) activity, and tissue and plasma triiodothyronine (T3) content determined at 9.5 months of age. 2. Body weights (BW) of obese greater than lean, and were greater when fed the SU than CS diet in both phenotypes. Phenotype effects (obese greater than lean) were present for fat pad weights and adipose cellularity in most primary adipose tissue depots, and diet effects (SU greater than CS) were present for epididymal and retroperitoneal depots in both phenotypes. 3. Interscapular brown adipose tissue (IBAT) and IBAT:BW ratios of obese greater than lean, and diet effects (SU greater than CS) were present for lean but not obese rats. Liver T4-5'DI activity and plasma and tissue T3 of lean greater than obese, while IBAT 5'DI activity of obese greater than lean in the CS diet. 4. These results indicate that obesity occurs in the SHR/N-cp rat as the result of hypertrophy and hyperplasia of adipose tissue, and that isoenergetic substitution of simple for complex carbohydrate exaggerates fat accretion in lean but not obese rats. Moreover, the obesity occurs in spite of greater mass, cellularity, and T4-5'DI activity of IBAT, consistent with a thermogenic defect in the obese phenotype of this strain.
Asunto(s)
Tejido Adiposo/fisiología , Diabetes Mellitus/fisiopatología , Carbohidratos de la Dieta/farmacología , Yoduro Peroxidasa/metabolismo , Hígado/enzimología , Obesidad , Tejido Adiposo/enzimología , Tejido Adiposo Pardo/enzimología , Animales , Peso Corporal , Recuento de Células , Diabetes Mellitus Experimental/enzimología , Diabetes Mellitus Experimental/fisiopatología , Hígado/efectos de los fármacos , Masculino , Fenotipo , Ratas , Ratas Endogámicas SHR , Triyodotironina/sangreRESUMEN
1. Groups of lean and obese LA/N-cp rats were administered the intestinal glucosidase inhibitor acarbose at 150 or 300 mg/kg diet from 7 until 17 weeks of age and the effects of the drug on food intake patterns and adiposity determined. 2. Dose related effects on body weights, adiposity and feed efficiency ratio were observed (control greater than 150 mg greater than 300 mg drug/kg diet) following treatment in both phenotypes, with the greatest differences observed in the obese phenotype. 3. Acarbose at both dosages was associated with phenotype-specific alterations in food intake amount and feeding pattern, resulting in an attenuation of age-associated increases in food intake. The feed efficiency ratio decreased in both phenotypes, and approached normally fed lean controls in obese rats administered the greater dosage. 4. These results indicate that patterns of food intake and weight gain differ markedly between lean and obese rats of this strain, and acarbose brings about a dose-related attenuation of developing food intake patterns in both phenotypes and which are associated with decreases in weight gain and adiposity. Thus, this drug may have therapeutic potential as an adjunct agent in the treatment of obesity and/or other disorders of carbohydrate intolerance.
Asunto(s)
Tejido Adiposo/crecimiento & desarrollo , Ingestión de Alimentos/efectos de los fármacos , Inhibidores de Glicósido Hidrolasas , Trisacáridos/farmacología , Aumento de Peso/efectos de los fármacos , Acarbosa , Tejido Adiposo/efectos de los fármacos , Animales , Dieta , Obesidad/genética , Obesidad/prevención & control , Ratas , Ratas MutantesRESUMEN
1. Groups of lean and obese LA/N-cp and obese Type II diabetic SHR/N-cp rats were fed semisynthetic diets with or without the alpha-glucosidase inhibitor acarbose (ACB, 100 mg/kg diet, p.o.) from 8 until 15 weeks of age, and measures of fasting serum total cholesterol (TC), insulin (INS), and hepatic HMG-CoA synthase activity determined at the end of the study. 2. ACB was without marked effect on mean food intake in either strain or either phenotype, and resulted in less weight gain and decreased adipose mass in obese LA/N-cp rats. INS was greater in the obese than the lean phenotype of both strains, and ACB resulted in greater reductions in INS in obese LA/N-cp than in obese LA/N-cp rats. 3. Serum TC concentrations were greater in the obese than in the lean phenotype of both strains, and ACB resulted in decreases in TC in both strains and in lower beta:alpha lipoprotein cholesterol ratios in obese LA/N-cp rats. Liver HMG Co-A synthase activity was greater in lean than obese rats and ACB resulted in normalization of enzyme activity in obese LA/N-cp but not SHR/N-cp rats. 4. These results confirm the hypercholesterolemia which occurs in the obese phenotype of the corpulent rat strains, and indicates that ACB may bring about significant reductions in body weight and fatness, TC, and in improved beta:alpha lipoprotein ratios and HMG-CoA synthase activity in obesity.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Colesterol/biosíntesis , Glucosidasas/antagonistas & inhibidores , Intestinos/enzimología , Hígado/metabolismo , Obesidad/metabolismo , Trisacáridos/farmacología , Acarbosa , Animales , Colesterol/sangre , Diabetes Mellitus/sangre , Ingestión de Alimentos/fisiología , Hidroximetilglutaril-CoA Sintasa/metabolismo , Insulina/sangre , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas , Aumento de Peso/fisiologíaRESUMEN
1. The effects of diet and norepinephrine (NE) on resting metabolic rate (RMR) were determined using indirect calorimetry in 6-month-old lean and corpulent LA/N-cp rats. RMRs of lean rats were greater than the corpulent. 2. Ingestion of carbohydrate (CHO) in the unfasted and fasted states increased the RMR of both groups, especially in the lean phenotype when compared to oil. 3. Serum T3 and glucose concentrations were similar in both phenotypes. 4. The effects of NE on RMR were maximal after a 200 micrograms NE/kg body weight injections.
Asunto(s)
Metabolismo Basal/fisiología , Peso Corporal/fisiología , Dieta , Norepinefrina/farmacología , Estado Nutricional/fisiología , Obesidad/fisiopatología , Animales , Metabolismo Basal/efectos de los fármacos , Masculino , Obesidad/metabolismo , RatasRESUMEN
1. Groups of lean and corpulent LA/N-cp rats were fed isoenergetic diets containing, 54% carbohydrate as maize starch (MS) or sucrose (SU), 20% protein, 16% mixed fats, plus other essential nutrients and fiber from 1.5-9 months of age. Final body weights of corpulent rats were 2-3 times those of their lean littermates, and were greater with SU than MS diet in both phenotypes. 2. Interscapular brown adipose tissue (IBAT) mass was greater in corpulent than lean and was greater with SU than MS diet in lean but not corpulent rats. IBAT cell diameters and adipocyte volumes were generally similar in both phenotypes, and were not markedly affected by dietary carbohydrate type. 3. Brown adipocyte locularity profiles were qualitatively similar in both phenotypes, and were morphologically indicative of thermogenic activity in both phenotypes. Locule profiles of corpulent animals contained a greater proportion of thermogenically less active types IV and V brown adipocytes than similarly fed lean animals, however, and locule distribution profiles were not influenced by diet. 4. Serum T3 concentrations were similar in both phenotypes, were greater in SU than MS lean rats and were not influenced by diet in the corpulent phenotype. In contrast, serum thyroxine concentrations and percent thyroxine uptake were not influenced by diet or phenotype. 5. These results are consistent with a partial impairment in BAT-mediated thermogenic activity in the corpulent phenotype and suggest that obesity in this strain may be due to factors other than biochemically defective brown adipose tissue thermogenesis.
Asunto(s)
Tejido Adiposo Pardo/patología , Carbohidratos de la Dieta/farmacología , Obesidad/sangre , Tiroxina/sangre , Triyodotironina/sangre , Tejido Adiposo Pardo/efectos de los fármacos , Animales , Metabolismo de los Lípidos , Obesidad/genética , Obesidad/patología , Fenotipo , Radioinmunoensayo , Ratas , Ratas Endogámicas , Triyodotironina/metabolismoRESUMEN
1. Characteristics of resting and of norepinephrine (NE)-stimulated thermogenesis, and the glycemic response to NE were determined in adult male Wistar Fatty rats. Rats were maintained on Purina chow No. 5001 until 22 weeks of age, and fed semisynthetic diets containing 54% carbohydrate, 20% protein, 16% mixed fats, plus essential vitamins, minerals, and non-nutritive fiber from 22 until 30 weeks of age. 2. Obese rats were 50% heavier than lean throughout the study. Phenotype effects (obese greater than lean) were present for retroperitoneal (RP) and dorsal (DOR) white fat depot weight, adipocyte number per depot, and adipocyte lipid content. Epididymal mass and cellularity were similar in both phenotypes. 3. Interscapular brown adipose tissue (IBAT) mass, adipocyte size, and adipocyte number were greater in obese than in lean. Resting metabolic rates (RMR) of obese rats were lower than in lean, and increased 79% in lean but only 33% in obese animals following NE (200 micrograms/kg BW, s.c.) stimulation. 4. The glycemic response to NE occurred normally in both phenotypes, and resulted in a 3-fold increment in plasma glucose in lean rats and a 5-6-fold increase in plasma glucose in obese rats. 5. The results of this study are consistent with hyperplasia and hypertrophy of IBAT, RP and DOR depots, and indicate that the capacity for non-shivering thermogenesis is impaired in the obese phenotype of this strain in spite of peripheral sensitivity to NE and greater mass and cellularity of brown adipose tissue.
Asunto(s)
Regulación de la Temperatura Corporal , Diabetes Mellitus Experimental/complicaciones , Obesidad/etiología , Tejido Adiposo/patología , Animales , Glucemia/análisis , Peso Corporal , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/fisiopatología , Masculino , Norepinefrina/farmacología , Ratas , Ratas MutantesRESUMEN
Groups of lean or pre-obese LA/N-cp rats were subjected to a program of vigorous exercise (less than 4 hr/day) or remained sedentary from 6 weeks until 12 weeks of age. Sedentary pre-obese rats gained weight twice as rapidly as sedentary lean rats. Exercise treatment resulted in greater decrements in body wt in obese than in lean rats, but did not result in absolute weight loss in either group. At 12 weeks of age, fat pad weights in principle depots were 10-15 times greater in corpulent than in lean rats and were significantly smaller in the exercised groups of both phenotypes, and corresponded with lower relative adiposity compared to corresponding sedentary groups. Heart weights were greater in corpulent than lean, while gastrocnemius muscle weights were similar in both phenotypes. Exercise was without effect on the weight of either muscle tissue in either phenotype. Interscapular brown adipose tissue weights and the IBAT:BW ratio were greater in obese than in lean rats. IBAT weights were lower in exercised than sedentary rats of either phenotype, but the IBAT:BW ratio was lower only in the obese exercised rats. In sedentary rats, L-alpha-glycerophosphate dehydrogenase and malic enzyme activity were greater in obese than lean, and exercise treatment resulted in increased L-alpha-glycerophosphate dehydrogenase and malic enzyme only in lean rats. These results are consistent with a redistribution of energy expenditure from energy storing to energy dissipating pathways following vigorous exercise, resulting in slowed rates of weight gain and body fat accretion in both lean and obese animals, with the most significant decrements among pre-obese rats.
Asunto(s)
Tejido Adiposo/fisiología , Metabolismo Energético , Obesidad/fisiopatología , Animales , Peso Corporal , Femenino , Genotipo , Obesidad/genética , Esfuerzo Físico , Ratas , Ratas MutantesRESUMEN
Pre-obese LA/N-cp rats consumed more food and gained weight more rapidly than their lean littermates, and measures of adipose tissue depots indicated that the excess weight was deposited principally as carcass fat. Serum T3 concentrations and resting metabolic rates were lower in corpulent than in lean animals, consistent with a greater efficiency of weight gain in those animals. In vitro measures of T3 neogenesis from T4 were lower in corpulent than in lean animals in liver, kidney, and skeletal muscle and greater in interscapular brown adipose tissue. The intracellular generation of T3 from T4 is a fundamental component of the normal adaptive response to alterations in diet and environment, and is an essential prerequisite for the expression of non-shivering thermogenesis. These results are consistent with a functional impairment in the activity of the enzyme T4-5'-deiodinase in peripheral tissues, and suggest that this impairment is contributory if not causative of obesity in this strain of rat.
Asunto(s)
Obesidad/metabolismo , Triyodotironina/biosíntesis , Tejido Adiposo/metabolismo , Animales , Regulación de la Temperatura Corporal , Peso Corporal , Yoduro Peroxidasa/análisis , Consumo de Oxígeno , Proteínas/metabolismo , RatasRESUMEN
Resting metabolic rate (RMR), as well as caffeine (CAF) and ephedrine (EPH) stimulated thermogenesis (VO2) were measured in young adult corpulent (corp) LA/N-cp (LA-corpulent) rats. RMR of lean was greater than corp. Administration of EPH, CAF and EPH + CAF resulted in 32, 48 and 50% increases in VO2, respectively, in both lean and corp rats. The time to attain maximal VO2 was similar for both drugs in both phenotypes, but the duration of maximal VO2 averaged 50, 26 and 42% longer in corp than lean for EPH, CAF and EPH + CAF, respectively. Acute weight loss following these treatments was greater for corp than lean, and corresponded with the duration of elevated VO2. These results are consistent with a normally functioning end-organ sympathomimetic receptor system in the corp phenotype of the LA/N-cp rat, and suggest that obesity in this model may be caused by factors other than defective brown fat thermogenesis at the end organ level.
Asunto(s)
Regulación de la Temperatura Corporal/efectos de los fármacos , Cafeína/farmacología , Efedrina/farmacología , Obesidad/fisiopatología , Tejido Adiposo Pardo/efectos de los fármacos , Tejido Adiposo Pardo/fisiopatología , Animales , Femenino , Obesidad/genética , Ratas , Ratas MutantesRESUMEN
The effects of isoenergetic sucrose and starch-based diets on thermogenesis were investigated in young adult, male, lean and corpulent SHR/N-cp rats. Corpulent rats gained weight 1.5 times more rapidly than lean, and sucrose diets resulted in more rapid weight gains in both phenotypes. Rates of resting and of norepinephrine-stimulated oxygen consumption were similar in both groups of lean rats and in sucrose-fed corpulent rats, but were decreased in starch-fed corpulent rats. The thermic response to injected norepinephrine occurred normally in all groups. Colonic and rectal temperatures were greater in lean than in corpulent rats. Acute cold exposure (5 degrees C) resulted in decreases in rectal but not colonic temperature in lean rats fed both diets, but resulted in lower temperatures at both sites in corpulent rats, with the greatest decreases being observed in the starch fed corpulent rats. Fifty percent of the corpulent but none of the lean rats succumbed within 24-48 hours following cold exposure. Urinary vanilmandelic acid (VMA) excretion was greater in lean than in corpulent rats, and the sucrose diet induced a greater increment in urinary VMA excretion in lean rats than in corpulent rats. These results are consistent with an impaired activation of sympathetically-mediated thermogenesis via nutritional or environmental stimuli in the corpulent genotype of the SHR/N-cp rat in concert with an economy in energy expenditure which may be contributing factors in the causation of their obese state.