RESUMO
AIMS: Investigate the role of melatonin on the regulation of body temperature in aged animals that have impaired melatonin production. MATERIAL AND METHODS: Aged Male Wistar rats were randomly assigned to the following groups: 1) control (vehicle added to the water bottles during the dark phase) and 2) melatonin-treated (10 mg/kg melatonin added to the water bottles during the dark phase). Before and after 16 weeks of vehicle or melatonin treatment, control group and melatonin-treated animals were acutely exposed to 18 °C for 2 h for an acute cold challenge and thermal images were obtained using an infrared camera. After 16 weeks, animals were euthanized and brown and beige adipocytes were collected for analysis of genes involved in the thermogenesis process by real-time PCR, and the uncoupling protein expression was evaluated by immunoblotting. Browning intensity of beige adipocytes were quantified by staining with hematoxylin-eosin. KEY FINDINGS: Chronic melatonin supplementation induced a minor increase in body mass and increased the animal's thermogenic potential in the cold acute challenge. Brown and beige adipocytes acted in a coordinated and complementary way to ensure adequate heat production. SIGNIFICANCE: Melatonin plays an important role in the thermoregulatory mechanisms, ensuring greater capacity to withstand cold and, also, participating in the regulation of energy balance.
Assuntos
Regulação da Temperatura Corporal/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Resposta ao Choque Frio/efeitos dos fármacos , Suplementos Nutricionais , Melatonina/farmacologia , Animais , Temperatura Baixa/efeitos adversos , Immunoblotting , Masculino , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase em Tempo RealRESUMO
PURPOSE: We studied subcutaneous white adipose tissue (sWAT) of obese mice submitted to intermittent fasting (IF). METHODS: Twelve-week-old C57BL/6 male mice received the diets Control (C) or high-fat (HF) for eight weeks (n = 20/each). Then, part of each group performed IF (24 h feeding/24 h fasting) for four weeks: C, C-IF, HF, and HF-IF (n = 10/each). RESULTS: Food intake did not show a difference in feeding and fasting days, but HF groups had a high energy intake. IF led to multilocular adipocytes in sWAT (browning), and improved respiratory quotient on the fed day. IF decreased gene expression of Leptin, but increased Adiponectin, ß3ar (beta3 adrenoreceptor), and Ucp1 (uncoupling protein). IF enhanced immunostaining of Caspase 3, Pcna (proliferating cell nuclear antigen), and UCP1 in sWAT. IF attenuated pro-inflammatory markers and pro-apoptotic markers in sWAT. CONCLUSIONS: IF in obese mice led to browning in sWAT adipocytes, enhanced thermogenesis, an improved adipose tissue pro-inflammatory profile.
Assuntos
Adipócitos Marrons/fisiologia , Adipócitos Brancos/fisiologia , Jejum/fisiologia , Obesidade/fisiopatologia , Gordura Subcutânea/citologia , Animais , Transdiferenciação Celular , Dieta Hiperlipídica , Ingestão de Energia/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/etiologia , Gordura Subcutânea/fisiologia , Termogênese/fisiologiaRESUMO
BACKGROUND: Exercise training may improve energy expenditure, thermogenesis, and oxidative capacities. Therefore, we hypothesized that physical training enhances white adipose tissue mitochondrial oxidative capacity from obese women. OBJECTIVE: To evaluate mitochondrial respiratory capacity, mitochondrial content, and UCP1 gene expression in white adipose tissue from women with obesity before and after the physical training program. METHODS: Women (n = 14, BMI 33 ± 3 kg/m2 , 35 ± 6 years, mean ± SD) were submitted to strength and aerobic exercises (75%-90% maximum heart rate and multiple repetitions), 3 times/week during 8 weeks. All evaluated subjects were paired, before and after training for resting metabolic rate (RMR), substrate oxidation (lipid and carbohydrate) by indirect calorimeter, deuterium oxide body composition, and aerobic maximum velocity (Vmax ) test. At the beginning and at the ending of the protocol, abdominal subcutaneous adipose tissue was collected to measure the mitochondrial respiration by high-resolution respirometry, mitochondrial content by citrate synthase (CS) activity, and UCP1 gene expression by RT-qPCR. RESULTS: Combined physical training increased RMR, lipid oxidation, and Vmax but did not change body weight/composition. In WAT, exercise increased CS activity, decreased mitochondrial uncoupled respiration and mRNA of UCP1. RMR was positively correlated with fat-free mass. CONCLUSION: Physical training promotes an increase in mitochondrial content without changing tissue respiratory capacity, a reduction in mitochondrial uncoupling degree and UCP1 mRNA expression in WAT. Finally, it improved the resting metabolic rate, lipid oxidation and physical performance, independent of the body changing free, or fat mass in obese women.
Assuntos
Tecido Adiposo Branco/fisiologia , Exercício Físico , Mitocôndrias/fisiologia , Obesidade/metabolismo , Proteína Desacopladora 1/metabolismo , Adulto , Metabolismo Basal , Composição Corporal , Feminino , Humanos , Metabolismo dos Lipídeos , Oxirredução , Consumo de OxigênioRESUMO
SCOPE: The mechanisms and involvement of uncoupling protein 1 (UCP1) in the protection from obesity and insulin resistance induced by intake of a high-fat diet rich in omega-3 (n-3) fatty acids are investigated. METHODS AND RESULTS: C57BL/6J mice are fed either a low-fat (control group) or one of two isocaloric high-fat diets containing either lard (HFD) or fish oil (HFN3) as fat source and evaluated for body weight, adiposity, energy expenditure, glucose homeostasis, and inguinal white and interscapular brown adipose tissue (iWAT and iBAT, respectively) gene expression, lipidome, and mitochondrial bioenergetics. HFN3 intake protected from obesity, glucose and insulin intolerances, and hyperinsulinemia. This is associated with increased energy expenditure, iWAT UCP1 expression, and incorporation of n-3 eicosapentaenoic and docosahexaenoic fatty acids in iWAT and iBAT triacylglycerol. Importantly, HFN3 is equally effective in reducing body weight gain, adiposity, and glucose intolerance and increasing energy expenditure in wild-type and UCP1-deficient mice without recruiting other thermogenic processes in iWAT and iBAT, such as mitochondrial uncoupling and SERCA-mediated calcium and creatine-driven substrate cyclings. CONCLUSION: Intake of a high-fat diet rich in omega-3 fatty acids protects both wild-type and UCP1-deficient mice from obesity and insulin resistance by increasing energy expenditure through unknown mechanisms.
Assuntos
Metabolismo Energético/efeitos dos fármacos , Óleos de Peixe/farmacologia , Intolerância à Glucose/dietoterapia , Obesidade/prevenção & controle , Proteína Desacopladora 1/genética , Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/efeitos dos fármacos , Tecido Adiposo Branco/metabolismo , Animais , Dieta Hiperlipídica/efeitos adversos , Metabolismo Energético/genética , Ácidos Graxos Ômega-3/análise , Ácidos Graxos Ômega-3/farmacologia , Óleos de Peixe/química , Intolerância à Glucose/genética , Camundongos Endogâmicos C57BL , Camundongos Knockout , Obesidade/etiologia , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo , Termogênese/efeitos dos fármacos , Termogênese/genética , Proteína Desacopladora 1/metabolismoRESUMO
Brown adipose tissue (BAT) influences energy balance through nonshivering thermogenesis, and its metabolism daily and seasonal variations are regulated by melatonin through partially known mechanisms. We evaluated the role of melatonin in BAT molecular machinery of male Control, pinealectomized (PINX), and melatonin-treated pinealectomized (PINX/Mel) adult rats. BAT was collected either every 3 hours over 24 hours or after cold or high-fat diet (HFD) acute exposure. HFD PINX animals presented decreased Dio2 expression, while HFD PINX/Mel animals showed increased Dio2, Ucp1, and Cidea expression. Cold-exposed PINX rats showed decreased Dio2 and Lhs expression, and melatonin treatment augmented Adrß3, Dio2, Ucp1, and Cidea expression. Daily profiles analyses showed altered Dio2, Lhs, Ucp1, Pgc1α, and Cidea gene and UCP1 protein expression in PINX animals, leading to altered rhythmicity under sub-thermoneutral conditions, which was partially restored by melatonin treatment. The same was observed for mitochondrial complexes I, II, and IV protein expression and enzyme activity. Melatonin absence seems to impair BAT responses to metabolic challenges, and melatonin replacement reverses this effect, with additional increase in the expression of crucial genes, suggesting that melatonin plays an important role in several key points of the thermogenic activation pathway, influencing both the rhythmic profile of the tissue and its ability to respond to metabolic challenges, which is crucial for the organism homeostasis.
Assuntos
Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Marrom/metabolismo , Melatonina/farmacologia , Animais , Temperatura Baixa , Dieta Hiperlipídica , Masculino , Pinealectomia , Ratos , Ratos WistarRESUMO
Brown adipose tissue (BAT) has recently been given more attention for the part it plays in obesity. BAT can generate great amounts of heat through thermogenesis by the activation of uncoupling protein 1 (UCP-1), which can be regulated by many environmental factors such as diet. Moreover, the build-up of BAT relates to maternal nutritional changes during pregnancy and lactation. However, at present, there is a limited number of studies looking at maternal nutrition and BAT development, and it seems that the research trend in this field has been considerably declining since the 1980s. There is much to discover yet about the role of different fatty acids on the development of BAT and the activation of UCP-1 during the fetal and the postnatal periods of life. A better understanding of the impact of nutritional intervention on the epigenetic regulation of BAT could lead to new preventive care for metabolic diseases such as obesity. It is important to know in which circumstances lipids could programme BAT during pregnancy and lactation. The modification of maternal dietary fatty acids, amount and composition, during pregnancy and lactation might be a promising strategy for the prevention of obesity in the offspring and future generations.
Assuntos
Tecido Adiposo Marrom/metabolismo , Dieta , Gorduras na Dieta/farmacologia , Ácidos Graxos/farmacologia , Fenômenos Fisiológicos da Nutrição Materna , Obesidade , Proteína Desacopladora 1/metabolismo , Animais , Gorduras na Dieta/metabolismo , Epigênese Genética , Ácidos Graxos/metabolismo , Feminino , Desenvolvimento Fetal , Humanos , Lactação , Obesidade/etiologia , Obesidade/metabolismo , Obesidade/prevenção & controle , Gravidez , TermogêneseRESUMO
The STE20/SPS1-related proline-alanine-rich protein kinase (SPAK) controls the activity of the electroneutral cation-chloride cotransporters (SLC12 family) and thus physiological processes such as modulation of cell volume, intracellular chloride concentration [Cl-]i, and transepithelial salt transport. Modulation of SPAK kinase activity may have an impact on hypertension and obesity, as STK39, the gene encoding SPAK, has been suggested as a hypertension and obesity susceptibility gene. In fact, the absence of SPAK activity in mice in which the activating threonine in the T loop was substituted by alanine (SPAK-KI mice) is associated with decreased blood pressure; however its consequences in metabolism have not been explored. Here, we fed wild-type and homozygous SPAK-KI mice a high-fat diet for 17 wk to evaluate weight gain, circulating substrates and hormones, energy expenditure, glucose tolerance, and insulin sensitivity. SPAK-KI mice exhibit resistance to HFD-induced obesity and hepatic steatosis associated with increased energy expenditure, higher thermogenic activity in brown adipose tissue, increased mitochondrial activity in skeletal muscle, and reduced white adipose tissue hypertrophy mediated by augmented whole body insulin sensitivity and glucose tolerance. Our data reveal a previously unrecognized role for the SPAK kinase in the regulation of energy balance, thermogenesis, and insulin sensitivity, suggesting that this kinase could be a new drug target for the treatment of obesity and the metabolic syndrome.
Assuntos
Dieta Hiperlipídica/efeitos adversos , Metabolismo Energético/genética , Resistência à Insulina/genética , Proteínas Serina-Treonina Quinases/genética , Aumento de Peso/genética , Animais , Células Cultivadas , Gorduras na Dieta/farmacologia , Metabolismo Energético/efeitos dos fármacos , Técnicas de Introdução de Genes , Inativação Gênica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas Serina-Treonina Quinases/fisiologia , Aumento de Peso/efeitos dos fármacosRESUMO
Perinatal maternal high-fat (HF) diet programmes offspring obesity. Obesity is associated with overactivation of the endocannabinoid system (ECS) in adult subjects, but the role of the ECS in the developmental origins of obesity is mostly unknown. The ECS consists of endocannabinoids, cannabinoid receptors (cannabinoid type-1 receptor (CB1) and cannabinoid type-2 receptor (CB2)) and metabolising enzymes. We hypothesised that perinatal maternal HF diet would alter the ECS in a sex-dependent manner in white and brown adipose tissue of rat offspring at weaning in parallel to obesity development. Female rats received standard diet (9 % energy content from fat) or HF diet (29 % energy content from fat) before mating, during pregnancy and lactation. At weaning, male and female offspring were killed for tissue harvest. Maternal HF diet induced early obesity, white adipocyte hypertrophy and increased lipid accumulation in brown adipose tissue associated with sex-specific changes of the ECS's components in weanling rats. In male pups, maternal HF diet decreased CB1 and CB2 protein in subcutaneous adipose tissue. In female pups, maternal HF diet increased visceral and decreased subcutaneous CB1. In brown adipose tissue, maternal HF diet increased CB1 regardless of pup sex. In addition, maternal HF diet differentially changed oestrogen receptor across the adipose depots in male and female pups. The ECS and oestrogen signalling play an important role in lipogenesis, adipogenesis and thermogenesis, and we observed early changes in their targets in adipose depots of the offspring. The present findings provide insights into the involvement of the ECS in the developmental origins of metabolic disease induced by inadequate maternal nutrition in early life.
Assuntos
Tecido Adiposo/metabolismo , Dieta Hiperlipídica/efeitos adversos , Endocanabinoides/metabolismo , Fenômenos Fisiológicos da Nutrição Materna , Obesidade/etiologia , Receptores de Canabinoides/metabolismo , Desmame , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Adiposidade , Fenômenos Fisiológicos da Nutrição Animal , Animais , Gorduras na Dieta/administração & dosagem , Gorduras na Dieta/efeitos adversos , Feminino , Lactação , Metabolismo dos Lipídeos , Masculino , Obesidade/metabolismo , Gravidez , Fenômenos Fisiológicos da Nutrição Pré-Natal , Ratos Wistar , Receptores de Estrogênio/metabolismo , Fatores Sexuais , TermogêneseRESUMO
Brown adipose tissue (BAT) is mainly composed of adipocytes, it is highly vascularized and innervated, and can be activated in adult humans. Brown adipocytes are responsible for performing non-shivering thermogenesis, which is exclusively mediated by uncoupling protein (UCP) -1 (a protein found in the inner mitochondrial membrane), the hallmark of BAT, responsible for the uncoupling of the proton leakage from the ATP production, therefore, generating heat (i.e. thermogenesis). Besides UCP1, other compounds are essential not only to thermogenesis, but also to the proliferation and differentiation of BAT, including peroxisome proliferator-activated receptor (PPAR) family, PPARgamma coactivator 1 (PGC1)-alpha, and PRD1-BF-1-RIZ1 homologous domain protein containing protein (PRDM) -16. The sympathetic nervous system centrally regulates thermogenesis through norepinephrine, which acts on the adrenergic receptors of BAT. This bound leads to the initialization of the many pathways that may activate thermogenesis in acute and/or chronic ways. In summary, this mini-review aims to demonstrate the latest advances in the knowledge of BAT.
Assuntos
Adipócitos/metabolismo , Tecido Adiposo Marrom/crescimento & desenvolvimento , Diferenciação Celular/genética , Termogênese/genética , Trifosfato de Adenosina/metabolismo , Tecido Adiposo Marrom/metabolismo , Animais , Proliferação de Células/genética , Proteínas de Ligação a DNA/biossíntese , Proteínas de Ligação a DNA/genética , Humanos , Camundongos , Norepinefrina/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/biossíntese , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Fatores de Transcrição/biossíntese , Fatores de Transcrição/genética , Proteína Desacopladora 1/biossíntese , Proteína Desacopladora 1/genéticaRESUMO
PURPOSE: Fish oil (FO) elicits diverse beneficial effects. Reduction in or prevention of body mass (BM) gain in animal models may be associated with modulation of brown adipose tissue (BAT). We aimed to evaluate the effects of different high-fat diets with FO on BAT metabolism and thermogenic markers. METHODS: C57BL/6 male mice (3-month-old) were fed different diets during 8 weeks: standard-chow diet (SC 10% fat), high-fat lard diet (HF-L 50% fat), high-fat lard plus FO diet (HF-L+FO 50% fat), and high-fat FO diet (HF-FO 50% fat). We evaluated BM and performed an oral glucose tolerance test. At euthanasia, plasma was collected for leptin, and triacylglycerol measurement and interscapular BAT was dissected and stored for molecular analyses. RESULTS: HF-L group showed elevated BM; glucose intolerance associated with diminished TC10 and GLUT4 expressions; hypertriglyceridemia associated with increased CD36 and diminished CPT1 expression; elevated expression of pro-inflammatory cytokines; and reduced PPAR expression. Furthermore, these animals showed hyperleptinemia with increased expression of thermogenic markers (beta3-AR, PGC1alpha, and UCP1). Conversely, HF-L+FO and HF-FO groups showed reduced BM gain with regularization of glucose tolerance and triglyceridemia, GLUT4, TC10, CD36, CPT1, and cytokines expressions. Both groups exhibited elevated PPAR and thermogenic markers expression in a dose-dependent way. CONCLUSIONS: FO improves metabolic profile and upregulates thermogenic markers, suggesting an elevated thermogenesis that leads to reduced BM gain.