RESUMO
The aim of this study was to evaluate whether high-fat (HF) diet intake during puberty can program obesity as well as generate glucose imbalance and hepatic metabolic dysfunctions in adult life. Male Wistar rats were randomly assigned into two groups: rats fed standard chow (NF) and rats fed a HF from postnatal 30-day-old (PND30) until PND60. Then, both groups were fed a standard chow from PND60 until PND120. Euthanasia and samples collections occurred at PND120. HF animals were overweight (+11%) and had increased adiposity, hyperphagia (+12%), hyperglycaemia (+13%), hyperinsulinemia (+69%), and hypertriglyceridemia (+34%). Plasma glucose levels during intravenous glucose tolerance test (ivGTT) and intraperitoneal insulin tolerance test (ipITT) were also higher in the HF group, whereas Kitt was significantly lower (-34%), suggesting reduced insulin sensitivity. In the same sense, HF animals present pancreatic islets hypertrophy and high ß-cell mass. HF animals also had a significant increase in blood glucose levels during pyruvate tolerance test, indicating increased gluconeogenesis. Hepatic morphology analyses showed an increase in lipid inclusion in the HF group. Moreover, PEPCK and FAS protein expression were higher in the livers of the HF animals (+79% and + 37%, respectively). In conclusion, HF during puberty causes obese phenotype leading to glucose dyshomeostasis and nonalcoholic fatty liver disease, which can be related to the overexpression of proteins PEPCK and FAS.
Assuntos
Glicemia , Dieta Hiperlipídica , Ratos , Masculino , Animais , Dieta Hiperlipídica/efeitos adversos , Glicemia/análise , Ratos Wistar , Maturidade Sexual , Obesidade/complicações , Obesidade/metabolismo , Glucose/metabolismoRESUMO
Perturbations to nutrition during critical periods are associated with changes in embryonic, fetal or postnatal developmental patterns that may render the offspring more likely to develop cardiovascular disease in later life. The aim of this study was to evaluate whether autonomic nervous system imbalance underpins in the long-term hypertension induced by dietary protein restriction during peri-pubertal period. Male Wistar rats were assigned to groups fed with a low protein (4% protein, LP) or control diet (20.5% protein; NP) during peri-puberty, from post-natal day (PN) 30 until PN60, and then all were returned to a normal protein diet until evaluation of cardiovascular and autonomic function at PN120. LP rats showed long-term increased mean arterial pressure (p = 0.002) and sympathetic arousal; increased power of the low frequency (LF) band of the arterial pressure spectral (p = 0.080) compared with NP animals. The depressor response to the ganglion blocker hexamethonium was increased in LP compared with control animals (p = 0.006). Pulse interval variability showed an increase in the LF band and LF/HF ratio (p = 0.062 and p = 0.048) in LP animals. The cardiac response to atenolol and/or methylatropine and the baroreflex sensitivity were similar between groups. LP animals showed ventricular hypertrophy (p = 0.044) and increased interstitial fibrosis (p = 0.028) compared with controls. Reduced protein carbonyls (PC) (p = 0.030) and catalase activity (p = 0.001) were observed in hearts from LP animals compared with control. In the brainstem, the levels of PC (p = 0.002) and the activity of superoxide dismutase and catalase (p = 0.044 and p = 0.012) were reduced in LP animals, while the levels of GSH and total glutathione were higher (p = 0.039 and p = 0.038) compared with NP animals. Protein restriction during peri-pubertal period leads to hypertension later in life accompanied by sustained sympathetic arousal, which may be associated with a disorganization of brain and cardiac redox state and structural cardiac alteration.
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BACKGROUND: Early postnatal overfeeding (PO) induces long-term overweight and reduces brown adipose tissue (BAT) thermogenesis. Exercise has been suggested as a possible intervention to increase BAT function. In this study, we investigated chronical effects of moderate-intensity exercise in BAT function in postnatal overfed male Wistar rats METHODS: Litters' delivery was on postnatal-day 0 - PN0. At PN2, litters were adjusted to nine (normal litter - NL) or three pups (small litter - SL) per dam. Animals were weaned on PN21 and in PN30 randomly divided into sedentary (NL-Sed and SL-Sed) or exercised (NL-Exe and SL-Exe), N of 14 litters per group. Exercise protocol started (PN30) with an effort test; training sessions were performed three times weekly at 60% of the VO2max achieved in effort test, until PN80. On PN81, a temperature transponder was implanted beneath the interscapular BAT, whose temperature was assessed in periods of lights-on and -off from PN87 to PN90. Sympathetic nerve activation of BAT was registered at PN90. Animals were euthanized at PN91 and tissues collected RESULTS: PO impaired BAT thermogenesis in lights-on (pPO < 0.0001) and -off (pPO < 0.01). Exercise increased BAT temperature in lights-on (pExe < 0.0001). In NL-Exe, increased BAT activity was associated with higher sympathetic activity (pExe < 0.05), ß3-AR (pExe < 0.001), and UCP1 (pExe < 0.001) content. In SL-Exe, increasing BAT thermogenesis is driven by a combination of tissue morphology remodeling (pExe < 0.0001) with greater effect in increasing UCP1 (pExe < 0.001) and increased ß3-AR (pExe < 0.001) content. CONCLUSION: Moderate exercise chronically increased BAT thermogenesis in both, NL and SL groups. In NL-Exe by increasing Sympathetic activity, and in SL-Exe by a combination of increased ß3-AR and UCP1 content with morphologic remodeling of BAT. Chronically increasing BAT thermogenesis in obese subjects may lead to higher overall energy expenditure, favoring the reduction of obesity and related comorbidities.
Assuntos
Tecido Adiposo Marrom/metabolismo , Obesidade/fisiopatologia , Condicionamento Físico Animal/fisiologia , Animais , Brasil , Modelos Animais de Doenças , Camundongos , Obesidade/diagnóstico , Condicionamento Físico Animal/métodos , Ratos Wistar/crescimento & desenvolvimento , Ratos Wistar/metabolismoRESUMO
We aimed to test whether moderate physical training can induce long-lasting protection against cardiovascular risk factors induced by high fat diet (HFD) intake, even after cessation of training. 90-days-old Wistar rats were submitted to a sedentary lifestyle or moderate physical training, three times a week, for 30 days. Following this, at 120 days-of age, sedentary and trained rats received a hypercaloric diet (HFD) or a commercial diet normal fat diet (NFD) for 30 days. Body weight (BW) and food intake were evaluated weekly. At 150 days-of age, hemodynamic measures (systolic, diastolic, mean blood pressure, pulse pressure, pulse interval and heart rate) were made via an indwelling femoral artery catheter. Beat-to-beat data were analyzed to calculate power spectra of systolic blood pressure (SBP) and pulse interval. After euthanasia, mesenteric fat pads were removed and weighted and total blood was stored for later analysis of lipid profile. Consumption of a HFD increased blood pressure (BP), pulse pressure, low frequency BP variability, BW gain, fat pad stores and induced dyslipidemia. Interestingly, prior physical training was able to partially protect against this rise in BP and body fat stores. Prior physical training did not totally protect against the effects of HFD consumption but previously trained animals did demonstrate resistance to the development of cardiometabolic alterations, which illustrate that the benefits of physical training may be partially maintained even after 30 days of detraining period.
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An interaction between obesity, impaired glucose metabolism and sperm function in adults has been observed but it is not known whether exposure to a diet high in fat during the peri-pubertal period can have longstanding programmed effects on reproductive function and gonadal structure. This study examined metabolic and reproductive function in obese rats programmed by exposure to a high fat (HF) diet during adolescence. The effect of physical training (Ex) in ameliorating this phenotype was also assessed. Thirty-day-old male Wistar rats were fed a HF diet (35% lard w/w) for 30 days then subsequently fed a normal fat diet (NF) for a 40-day recovery period. Control animals were fed a NF diet throughout life. At 70 days of life, animals started a low frequency moderate exercise training that lasted 30 days. Control animals remained sedentary (Se). At 100 days of life, biometric, metabolic and reproductive parameters were evaluated. Animals exposed to HF diet showed greater body weight, glucose intolerance, increased fat tissue deposition, reduced VO2max and reduced energy expenditure. Consumption of the HF diet led to an increase in the number of abnormal seminiferous tubule and a reduction in seminiferous epithelium height and seminiferous tubular diameter, which was reversed by moderate exercise. Compared with the NF-Se group, a high fat diet decreased the number of seminiferous tubules in stages VII-VIII and the NF-Ex group showed an increase in stages XI-XIII. HF-Se and NF-Ex animals showed a decreased number of spermatozoa in the cauda epididymis compared with animals from the NF-Se group. Animals exposed to both treatments (HF and Ex) were similar to all the other groups, thus these alterations induced by HF or Ex alone were partially prevented. Physical training reduced fat pad deposition and restored altered reproductive parameters. HF diet consumption during the peri-pubertal period induces long-term changes on metabolism and the reproductive system, but moderate and low frequency physical training is able to recover adipose tissue deposition and reproductive system alterations induced by high fat diet. This study highlights the importance of a balanced diet and continued physical activity during adolescence, with regard to metabolic and reproductive health.
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Maternal obesity programmes a range of metabolic disturbances for the offspring later in life. Moreover, environmental changes during the suckling period can influence offspring development. Because both periods significantly affect long-term metabolism, we aimed to study whether cross-fostering during the lactation period was sufficient to rescue a programmed obese phenotype in offspring induced by maternal obesity following monosodium L-glutamate (MSG) treatment. Obesity was induced in female Wistar rats by administering subcutaneous MSG (4 mg/g body weight) for the first 5 days of postnatal life. Control and obese female rats were mated in adulthood. The resultant pups were divided into control second generation (F2) (CTLF2), MSG-treated second generation (F2) (MSGF2), which suckled from their CTL and MSG biological dams, respectively, or CTLF2-CR, control offspring suckled by MSG dams and MSGF2-CR, MSG offspring suckled by CTL dams. At 120 days of age, fat tissue accumulation, lipid profile, hypothalamic leptin signalling, glucose tolerance, glucose-induced, and adrenergic inhibition of insulin secretion in isolated pancreatic islets were analysed. Maternal MSG-induced obesity led to an obese phenotype in male offspring, characterized by hyperinsulinaemia, hyperglycaemia, hyperleptinaemia, dyslipidaemia, and impaired leptin signalling, suggesting central leptin resistance, glucose intolerance, impaired glucose-stimulated, and adrenergic inhibition of insulin secretion. Cross-fostering normalized body weight, food intake, leptin signalling, lipid profiles, and insulinaemia, but not glucose homeostasis or insulin secretion from isolated pancreatic islets. Our findings suggest that alterations during the lactation period can mitigate the development of obesity and prevent the programming of adult diseases.
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Modelos Animais de Doenças , Lactação , Fenômenos Fisiológicos da Nutrição Materna , Obesidade/prevenção & controle , Efeitos Tardios da Exposição Pré-Natal , Adiposidade , Animais , Animais Recém-Nascidos , Feminino , Desenvolvimento Fetal , Aromatizantes/administração & dosagem , Aromatizantes/efeitos adversos , Aditivos Alimentares/administração & dosagem , Aditivos Alimentares/efeitos adversos , Injeções Subcutâneas , Insulina/metabolismo , Secreção de Insulina , Ilhotas Pancreáticas/metabolismo , Masculino , Obesidade/etiologia , Obesidade/metabolismo , Gravidez , Ratos Wistar , Glutamato de Sódio/administração & dosagem , Glutamato de Sódio/efeitos adversos , Técnicas de Cultura de Tecidos , Aumento de PesoRESUMO
BACKGROUND: Serum lactate dehydrogenase is a non-specific marker for lymphoma whose prognostic significance is well established for both indolent and aggressive lymphomas at the time of diagnosis. The performance characteristics of this enzyme in predicting relapse in patients with diffuse large B-cell lymphoma has not been well studied. METHODS: This study compared serum lactate dehydrogenase levels in 27 patients with diffuse large B-cell lymphoma who relapsed after sustaining a complete response versus 87 patients who did not relapse. For relapsed patients, the serum lactate dehydrogenase level at relapse was compared with the level three months before (considered baseline). For non-relapsed patients, the last two levels during follow-up were compared. For statistical analysis the T-test was used to compare differences in mean values between groups. The sensitivity, specificity, positive and negative predictive values for serum lactate dehydrogenase in detecting relapse compared to confirmatory imaging were calculated. RESULTS: At relapse, only 33% patients had increases in serum lactate dehydrogenase above the upper limit of normal. The mean increase was 1.2-fold above the upper limit of normal for relapsed vs. 0.83 for those who did not relapse (p-value = 0.59). The mean increase in serum lactate dehydrogenase, from baseline, was 1.1-fold in non-relapsed vs. 1.3 in relapsed patients (p-value = 0.3). The likelihood ratio of relapse was 4.65 for patients who had 1.5-fold increases in serum lactate dehydrogenase above baseline (p-value = 0.03). The sensitivity, specificity, positive and negative predictive values of 1.5-fold increases for detecting relapse, compared to clinical and imaging findings were 0.18, 0.95, 0.55, and 0.79, respectively. CONCLUSION: A 1.5-fold increase in serum lactate dehydrogenase, over a period of 3 months, is associated with increased likelihood of relapse from diffuse large B-cell lymphoma.
RESUMO
Background: Serum lactate dehydrogenase is a non-specific marker for lymphoma whose prognostic significance is well established for both indolent and aggressive lymphomas at the time of diagnosis. The performance characteristics of this enzyme in predicting relapse in patients with diffuse large B-cell lymphoma has not been well studied. Methods: This study compared serum lactate dehydrogenase levels in 27 patients with diffuse large B-cell lymphoma who relapsed after sustaining a complete response versus 87 patients who did not relapse. For relapsed patients, the serum lactate dehydrogenase level at relapse was compared with the level three months before (considered baseline). For non-relapsed patients, the last two levels during follow-up were compared. For statistical analysis the T-test was used to compare differences in mean values between groups. The sensitivity, specificity, positive and negative predictive values for serum lactate dehydrogenase in detecting relapse compared to confirmatory imaging were calculated. Results: At relapse, only 33% patients had increases in serum lactate dehydrogenase above the upper limit of normal. The mean increase was 1.2-fold above the upper limit of normal for relapsed vs. 0.83 for those who did not relapse (p-value = 0.59). The mean increase in serum lactate dehydrogenase, from baseline, was 1.1-fold in non-relapsed vs. 1.3 in relapsed patients (p-value = 0.3). The likelihood ratio of relapse was 4.65 for patients who had 1.5-fold increases in serum ...
Assuntos
Humanos , Masculino , Linfoma não Hodgkin , Seguimentos , Linfoma Difuso de Grandes Células B , L-Lactato Desidrogenase , AntineoplásicosRESUMO
The distribution of non-Hodgkin lymphoma (NHL) subtypes differs around the world but a systematic study of Latin America has not been done. Therefore, we evaluated the relative frequencies of NHL subtypes in Central and South America (CSA). Five expert hematopathologists classified consecutive cases of NHL from 5 CSA countries using the WHO classification and compared them to 400 cases from North America (NA). Among the 1028 CSA cases, the proportions of B- and T-cell NHL and the sex distribution were similar to NA. However, the median age of B-cell NHL in CSA (59 years) was significantly lower than in NA (66 years; P < .0001). The distribution of high-grade (52.9%) and low-grade (47.1%) mature B-cell NHL in CSA was also significantly different from NA (37.5% and 62.5%; P < .0001). Diffuse large B-cell lymphoma was more common in CSA (40%) than in NA (29.2%; P < .0001), whereas the frequency of follicular lymphoma was similar in Argentina (34.1%) and NA (33.8%), and higher than the rest of CSA (17%; P < .001). Extranodal NK/T-cell NHL was also more common in CSA (P < .0001). Our study provides new objective evidence that the distribution of NHL subtypes varies significantly by geographic region and should prompt epidemiologic studies to explain these differences.
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Linfoma não Hodgkin/classificação , Linfoma não Hodgkin/diagnóstico , Argentina/epidemiologia , Brasil/epidemiologia , Chile/epidemiologia , Feminino , Guatemala/epidemiologia , Humanos , Linfoma não Hodgkin/epidemiologia , Masculino , Pessoa de Meia-Idade , Peru/epidemiologia , Organização Mundial da SaúdeRESUMO
The distribution of subtypes of non-Hodgkin lymphoma (NHL) in Latin America is not well known. This Chilean study included 207 consecutive cases of NHL diagnosed at five cancer centers in the capital, Santiago, and one center in Viña del Mar. All cases were reviewed and classified independently by five expert hematopathologists according to the 2001 World Health Organization classification of NHL. A consensus diagnosis of NHL was reached in 195 of the 207 cases (94%). B-cell lymphomas constituted 88% of NHL, and diffuse large B-cell lymphoma (DLBCL, 38.5%) and follicular lymphoma (25.1%) were the most common subtypes. There was a high frequency of marginal zone B-cell lymphoma (10.3%), as well as of extranodal natural killer (NK)/T-cell lymphoma, nasal type (2.6%) and adult T-cell leukemia/lymphoma (0.5%). Extranodal presentation was seen in 74 of the 195 cases (38%) and the most common extranodal presentation was in the stomach (37.6%). The most common gastric lymphoma was DLBCL (54.5%) followed by mucosa-associated lymphoid tissue (MALT) lymphoma (41%). Overall, the frequency of NHL subtypes in Chile is between that reported in Western and Eastern countries, which is probably a reflection of the admixture of ethnicities as well as the environment and socioeconomic status of its population.