RESUMO
This study investigated whether regulation of the renin-angiotensin system (RAS) by enalapril and/or aerobic exercise training (AET) causes browning of the subcutaneous white adipose tissue (sWAT). C57BL/6 mice were fed either a standard chow or a high-fat (HF) diet for 16 weeks. At Week 8, HF-fed animals were divided into sedentary (HF), enalapril (HF-E), AET (HF-T), and enalapril plus AET (HF-ET) groups. Subsequently, sWAT was extracted for morphometry, determination of RAS expression, and biomarkers of WAT browning. The HF group displayed adipocyte hypertrophy and induction of the classical RAS axis. Conversely, all interventions reduced adiposity and induced the counterregulatory RAS axis. However, only AET raised plasma irisin, increased peroxisome proliferator-activated receptor-γ coactivator-1α, and uncoupling protein-1 levels, and the expression of PR-domain containing 16 in sWAT. Therefore, we concluded that AET-induced sWAT browning was independent of the counterregulatory axis shifting of RAS in HF diet-induced obesity.
Assuntos
Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Marrom/fisiopatologia , Adiposidade/efeitos dos fármacos , Enalapril/farmacologia , Condicionamento Físico Animal/fisiologia , Corrida/fisiologia , Gordura Subcutânea/efeitos dos fármacos , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Tecido Adiposo Branco/fisiopatologia , Animais , Biomarcadores/metabolismo , Dieta Hiperlipídica/efeitos adversos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Obesidade/fisiopatologia , Sistema Renina-Angiotensina/efeitos dos fármacos , Gordura Subcutânea/metabolismo , Gordura Subcutânea/fisiopatologiaRESUMO
Objective: To evaluate whether brown adipose tissue (BAT) activity is altered in women with polycystic ovary syndrome (PCOS), and whether BAT activity correlates with plasma levels of irisin, a myokine that can induce BAT formation. Design: We performed a cross-sectional study including women with PCOS (n = 45) and a healthy control group (n = 25) matched by age and body mass index (BMI). Methods: BAT activity was measured using 18F-FDG positron emission tomography-computed tomography (PET-CT) and plasma irisin levels were measured by a validated enzyme immunoassay. Results: Total BAT activity was significantly reduced in women with PCOS (maximal standardized uptake value (SUVmax): median 7.4 g/mL, interquartile range 0.9-15.4) compared to controls (median 13.0 g/mL, interquartile range 4.7-18.4, P = 0.047). However, this difference was no longer significant after adjustment for waist circumference, a surrogate marker of central adiposity. In the PCOS group, BAT activity correlated negatively with BMI (Spearman's r = -0.630, P = 0.000) and waist circumference (r = -0.592, P = 0.000) but not with plasma irisin levels. Conclusions: BAT activity was reduced in women with PCOS possibly due to increased central adiposity. In PCOS women, BAT activity did not correlate with plasma irisin levels.
Assuntos
Tecido Adiposo Marrom/fisiopatologia , Síndrome do Ovário Policístico/fisiopatologia , Tecido Adiposo Marrom/diagnóstico por imagem , Adiposidade , Adolescente , Adulto , Índice de Massa Corporal , Estudos Transversais , Feminino , Fibronectinas/sangue , Fluordesoxiglucose F18 , Humanos , Estilo de Vida , Pessoa de Meia-Idade , Síndrome do Ovário Policístico/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Resultado do Tratamento , Circunferência da Cintura , Adulto JovemRESUMO
Maternal smoking is a risk factor for progeny obesity. We have previously shown, in a rat model of neonatal tobacco smoke exposure, a mild increase in food intake and a considerable increase in visceral adiposity in the adult offspring. Males also had secondary hyperthyroidism, while females had only higher T4. Since brown adipose tissue (BAT) hypofunction is related to obesity, here we tested the hypothesis that higher levels of thyroid hormones are not functional in BAT, suggesting a lower metabolic rate. We evaluated autonomic nerve activity in BAT and its function in adult rats that were exposed to tobacco smoke during lactation. At birth, litters were adjusted to 3 male and 3 female pups/litter. From postnatal day (PND) 3 to 21, Wistar lactating rats and their pups were divided into SE group, smoke-exposed in a cigarette smoking machine (4 times/day) and C group, exposed to filtered air. Offspring were sacrificed at PND180. Adult SE rats of both genders had lower interscapular BAT autonomic nervous system activity, with higher BAT mass but no change in morphology. BAT UCP1 and CPT1a protein levels were decreased in the SE groups of both genders. Male SE rats had lower ß3-AR, TRα1, and TRß1 expression while females showed lower PGC1α expression. BAT Dio2 mRNA and hypothalamic POMC and MC4R levels were similar between groups. Hypothalamic pAMPK level was higher in SE males and lower in SE females. Thus, neonatal cigarette smoke exposure induces lower BAT thermogenic capacity, which can be obesogenic at adulthood.
Assuntos
Tecido Adiposo Marrom/fisiopatologia , Biomarcadores/análise , Sistema Nervoso Simpático/fisiopatologia , Termogênese/fisiologia , Poluição por Fumaça de Tabaco/efeitos adversos , Tecido Adiposo Marrom/metabolismo , Animais , Animais Recém-Nascidos , Western Blotting , Feminino , Imuno-Histoquímica , Masculino , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Poluição por Fumaça de Tabaco/análiseRESUMO
Maternal smoking is a risk factor for progeny obesity. We have previously shown, in a rat model of neonatal tobacco smoke exposure, a mild increase in food intake and a considerable increase in visceral adiposity in the adult offspring. Males also had secondary hyperthyroidism, while females had only higher T4. Since brown adipose tissue (BAT) hypofunction is related to obesity, here we tested the hypothesis that higher levels of thyroid hormones are not functional in BAT, suggesting a lower metabolic rate. We evaluated autonomic nerve activity in BAT and its function in adult rats that were exposed to tobacco smoke during lactation. At birth, litters were adjusted to 3 male and 3 female pups/litter. From postnatal day (PND) 3 to 21, Wistar lactating rats and their pups were divided into SE group, smoke-exposed in a cigarette smoking machine (4 times/day) and C group, exposed to filtered air. Offspring were sacrificed at PND180. Adult SE rats of both genders had lower interscapular BAT autonomic nervous system activity, with higher BAT mass but no change in morphology. BAT UCP1 and CPT1a protein levels were decreased in the SE groups of both genders. Male SE rats had lower β3-AR, TRα1, and TRβ1 expression while females showed lower PGC1α expression. BAT Dio2 mRNA and hypothalamic POMC and MC4R levels were similar between groups. Hypothalamic pAMPK level was higher in SE males and lower in SE females. Thus, neonatal cigarette smoke exposure induces lower BAT thermogenic capacity, which can be obesogenic at adulthood.
Assuntos
Animais , Masculino , Feminino , Ratos , Tecido Adiposo Marrom/fisiopatologia , Biomarcadores/análise , Sistema Nervoso Simpático/fisiopatologia , Termogênese/fisiologia , Poluição por Fumaça de Tabaco/efeitos adversos , Tecido Adiposo Marrom/metabolismo , Animais Recém-Nascidos , Western Blotting , Imuno-Histoquímica , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Poluição por Fumaça de Tabaco/análiseRESUMO
Brown adipose tissue (BAT) dysfunction is associated with obesity and its comorbidities, such as hypertension, and the improvement of BAT function seems important for obesity management. Here we investigated the effects of dietary calcium supplementation on BAT autonomic nerve activity, sympathoadrenal function and cardiovascular parameters in adult obese rats that were raised in small litters (SL group). Three days after birth, SL litters were adjusted to three pups to induce early overfeeding. The control group remained with 10 pups/litter until weaning (NL group). At PN120, the SL group was randomly divided into the following: rats fed with standard chow (SL) and rats fed with dietary calcium carbonate supplementation (SL-Ca, 10g/kg chow). Animals were killed either at PN120 or PN180. At both ages, SL rats had higher BAT autonomic nervous system activity, mass and adipocyte area, as well as increased heart rate and blood pressure (systolic and diastolic); 2 months of calcium supplementation normalized these parameters. At PN180 only, UCP1 and TRß1 in BAT were decreased in SL rats. These changes were also prevented by calcium treatment. Also at PN180, the SL group presented higher tyrosine hydroxylase and adrenal catecholamine contents, as well as lower hypothalamic POMC and MC4R contents. Calcium supplementation did not revert these alterations. Thus, we demonstrated that dietary calcium supplementation was able to improve cardiovascular parameters and BAT thermogenesis capacity in adult animals that were early overfed during lactation.
Assuntos
Tecido Adiposo Marrom/efeitos dos fármacos , Fenômenos Fisiológicos da Nutrição Animal , Cálcio da Dieta/farmacologia , Hiperfagia/fisiopatologia , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Tecido Adiposo Marrom/fisiopatologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Índice de Massa Corporal , Sistema Cardiovascular/efeitos dos fármacos , Sistema Cardiovascular/metabolismo , Suplementos Nutricionais , Feminino , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Masculino , Obesidade/tratamento farmacológico , Pró-Opiomelanocortina/metabolismo , Ratos , Ratos Wistar , Receptor Tipo 4 de Melanocortina/metabolismo , Termogênese/efeitos dos fármacos , DesmameRESUMO
BACKGROUND: Obesity is related to obstructive sleep apnea-hypopnea syndrome (OSAHS), but its roles in OSAHS as cause or consequence are not fully clarified. Isocapnic intermittent hypoxia (IIH) is a model of OSAHS. We verified the effect of IIH on body weight and brown adipose tissue (BAT) of Wistar rats. METHODS: Nine-month-old male breeders Wistar rats of two groups were studied: 8 rats submitted to IIH and 5 control rats submitted to sham IIH. The rats were weighed at the baseline and at the end of three weeks, after being placed in the IIH apparatus seven days per week, eight hours a day, in the lights on period, simulating an apnea index of 30/hour. After experimental period, the animals were weighed and measured as well as the BAT, abdominal, perirenal, and epididymal fat, the heart, and the gastrocnemius muscle. RESULTS: Body weight of the hypoxia group decreased 17 +/- 7 grams, significantly different from the variation observed in the control group (p = 0,001). The BAT was 15% lighter in the hypoxia group and reached marginally the alpha error probability (p = 0.054). CONCLUSION: Our preliminary results justify a larger study for a longer time in order to confirm the effect of isocapnic intermittent hypoxia on body weight and BAT.
Assuntos
Tecido Adiposo Marrom/fisiopatologia , Modelos Animais de Doenças , Síndromes da Apneia do Sono/fisiopatologia , Redução de Peso/fisiologia , Animais , Peso Corporal , Hipóxia/induzido quimicamente , Hipóxia/fisiopatologia , Masculino , Ratos , Ratos WistarRESUMO
It has been reported that systemic injection of arginine vasopressin (AVP) induces a drop in body core temperature (T(c)), but little is known about the mechanisms involved. Because glutamate is an important excitatory neurotransmitter involved in a number of thermoregulatory actions, in the present study, we tested the hypothesis that glutamate plays a role in systemic AVP-induced hypothermia. Wistar rats were pretreated intracerebroventricularly (icv) with kynurenic acid, an antagonist of l-glutamate ionotropic receptors, alpha-methyl-(4-carboxyphenyl)glycine (MCPG), an antagonist of l-glutamate metabotropic receptors, or saline 15 min before intravenous injection of AVP (2 microg/kg) or saline. T(c), brown adipose tissue (BAT) temperature, blood pressure, heart rate, and tail skin temperature were measured continuously. Administration of saline icv followed by intravenous AVP caused a significant drop in T(c) brought about by a reduction in BAT thermogenesis and an increase in heat loss through the tail. MCPG treatment (icv) did not affect the fall in T(c) induced by AVP. Treatment with kynurenic acid (icv) abolished AVP-induced hypothermia but did not affect the AVP-evoked rise in blood pressure or drop in heart rate and BAT temperature. Heat loss through the tail was significantly reduced in animals injected with AVP and pretrated with kynurenic acid. These data indicate that ionotropic receptors of l-glutamate in the central nervous system participate in peripheral AVP-induced hypothermia by affecting heat loss through the tail.
Assuntos
Arginina Vasopressina , Ácido Glutâmico/metabolismo , Glicina/administração & dosagem , Hipotermia/induzido quimicamente , Hipotermia/fisiopatologia , Tecido Adiposo Marrom/fisiopatologia , Animais , Arginina Vasopressina/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Temperatura Corporal/efeitos dos fármacos , Regulação da Temperatura Corporal/efeitos dos fármacos , Antagonistas de Aminoácidos Excitatórios/administração & dosagem , Glicina/análogos & derivados , Frequência Cardíaca/efeitos dos fármacos , Injeções Intravenosas , Injeções Intraventriculares , Ácido Cinurênico/administração & dosagem , Masculino , Ratos , Ratos Wistar , Receptores de Glutamato Metabotrópico/antagonistas & inibidores , Cauda/fisiopatologia , Termogênese/efeitos dos fármacosRESUMO
The effects of long-term cold exposure on brown adipose tissue (BAT) thermogenesis in hypothyroid rats have been examined. Thyroid ablation was performed in normal rats after 2 mo of exposure to 4 degrees C, when BAT hypertrophy and thermogenic activity were maximal. After ablation, hypothyroid and normal controls remained in the cold for 2 additional months. At the end of the 4-mo cold exposure, all untreated hypothyroid rats were alive, had normal body temperature, and had gained an average 12.8% more weight than normal controls. Long-term cold exposure of hypothyroid rats markedly increased BAT weight, mitochondrial proteins, uncoupling protein (UCP)-1, mRNA for UCP-1, and oxygen consumption to levels similar to those seen in cold-exposed normal rats. The results indicate that thyroid hormones are required for increased thermogenic capacity to occur as an adaptation to long-term cold exposure. However, cold adaptation can be maintained in the absence of thyroid hormone.
Assuntos
Aclimatação , Tecido Adiposo Marrom/fisiologia , Temperatura Baixa , Termogênese , Glândula Tireoide/fisiologia , Tecido Adiposo Marrom/fisiopatologia , Animais , Antitireóideos/farmacologia , Peso Corporal , Proteínas de Transporte/metabolismo , Feminino , Gliceraldeído-3-Fosfato Desidrogenases/metabolismo , Hipotireoidismo/metabolismo , Hipotireoidismo/fisiopatologia , Canais Iônicos , Isoenzimas/metabolismo , Masculino , Proteínas de Membrana/metabolismo , Metimazol/farmacologia , Mitocôndrias/metabolismo , Proteínas Mitocondriais , Consumo de Oxigênio , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Glândula Tireoide/fisiopatologia , Fatores de Tempo , Proteína Desacopladora 1RESUMO
Intact or surgically thyroidectomized (Tx) adult male Wistar rats, weighing 150-200 g, were fed a standard chow diet (approximately 1.8 Cal/g) or a high calorie (approximately 3.8 Cal/g) diet (cafeteria diet) for up to 30 days. Daily energy intake was about 5-fold higher in the rats fed the cafeteria diet regardless of their thyroid status. The cafeteria diet caused the retroperitoneal white fat pad to increase by approximately 2-fold, the volume of isolated white adipocytes to increase by 2-fold, and the total body fat to increase by a factor of approximately 3, again regardless of thyroid status. It also increased basal metabolic rate by about 20% in intact rats and by about 50% in Tx rats. The brown fat thermal response to norepinephrine (NE) infusion was approximately 2-fold increased in the intact rats fed the cafeteria diet. However, in the Tx rats, the brown fat thermal response to NE was blunted regardless of the dietary regimen adopted. In both intact and Tx rats, the cafeteria diet increased total brown fat mitochondria, uncoupling protein percentage, and total brown fat uncoupling protein by about 3-, 2-, and 5-fold, respectively. Serum leptin levels also increased approximately 4-fold in intact rats fed the cafeteria diet. However, in Tx rats, leptin levels did not change significantly during overfeeding. In conclusion, hypothyroidism caused the brown fat to become unresponsive to NE, even after 1 month on the cafeteria diet. However, these rats were able to increase basal metabolic rate and, as assessed by several different parameters, did not gain fat beyond that observed in intact controls kept on a similar overfeeding schedule.