RESUMO
The study aimed to evaluate the effects of Pereskia aculeata Miller (ora-pro-nobis [OPN]) flour on body and biochemical parameters, thermogenic activity, and molecular expression of markers in the muscle tissue of mice subjected to resistance training (RT). Twelve mice were randomly assigned to two groups (n=6 animals/group): G1: control (Control) fed a standard diet + RT and G2: experimental (OPN) fed a diet based on OPN flour + RT. The RT consisted of a 6-week program using a vertical ladder combined with a fixed weight attached to the animal. Several parameters were measured, including assessment of body composition, biochemical markers, thermogenic activity, and molecular (mRNA expression of interleukin (IL)-6, fibronectin type III domain-containing protein 5 (FNDC5), peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), nuclear respiratory factor 1 (NRF1), and mitochondrial transcription factor A (TFAM). The OPN group exhibited a decrease in body weight and visceral adiposity, higher energy expenditure, and lipid oxidation rate. In addition, it was observed an increase in muscle volume and in mRNA expression levels of IL-6, FNDC5, PGC-1α, and TFAM. These findings suggest that OPN flour could be a nutritional option to enhance performance in RT.
Assuntos
Farinha , Interleucina-6 , Músculo Esquelético , Miocinas , Treinamento Resistido , Animais , Humanos , Masculino , Camundongos , Composição Corporal/efeitos dos fármacos , Metabolismo Energético , Fibronectinas/metabolismo , Fibronectinas/genética , Interleucina-6/genética , Interleucina-6/metabolismo , Músculo Esquelético/metabolismo , Miocinas/genética , Miocinas/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Condicionamento Físico Animal , Termogênese/efeitos dos fármacosRESUMO
OBJECTIVE AND DESIGN: Kinin B1 receptor (B1R) has a key role in adipocytes to protect against obesity and glycemic metabolism, thus becoming a potential target for regulation of energy metabolism and adipose tissue thermogenesis. MATERIAL OR SUBJECTS: Kinin B1 knockout mice (B1KO) were subjected to acute induction with CL 316,243 and chronic cold exposure. METHODS: Metabolic and histological analyses, gene and protein expression and RNA-seq were performed on interscapular brown adipose tissue (iBAT) and inguinal white adipose tissue (iWAT) of mice. RESULTS: B1KO mice, under acute effect of CL 316,243, exhibited increased energy expenditure and upregulated thermogenic genes in iWAT. They were also protected from chronic cold, showing enhanced non-shivering thermogenesis with increased iBAT mass (~ 90%) and recruitment of beige adipocytes in iWAT (~ 50%). Positive modulation of thermogenic and electron transport chain genes, reaching a 14.5-fold increase for Ucp1 in iWAT. RNA-seq revealed activation of the insulin signaling pathways for iBAT and oxidative phosphorylation, tricarboxylic acid cycle, and browning pathways for iWAT. CONCLUSION: B1R deficiency induced metabolic and gene expression alterations in adipose tissue, activating thermogenic pathways and increasing energy metabolism. B1R antagonists emerge as promising therapeutic targets for regulating obesity and associated metabolic disorders, such as inflammation and diabetes.
Assuntos
Tecido Adiposo Marrom , Tecido Adiposo Branco , Dioxóis , Camundongos Knockout , Receptor B1 da Bradicinina , Termogênese , Animais , Masculino , Camundongos , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Branco/metabolismo , Tecido Adiposo Branco/efeitos dos fármacos , Agonistas de Receptores Adrenérgicos beta 3/farmacologia , Temperatura Baixa , Dioxóis/farmacologia , Metabolismo Energético/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Receptor B1 da Bradicinina/genética , Receptor B1 da Bradicinina/metabolismo , Receptores Adrenérgicos beta 3/genética , Receptores Adrenérgicos beta 3/metabolismo , Termogênese/efeitos dos fármacos , Tiazóis/farmacologia , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismoRESUMO
Undernutrition (UN) increases child vulnerability to illness and mortality. Caused by a low amount and/or poor quality of food intake, it impacts physical, cognitive, and social development. Modern types of food consumption have given highly processed food a higher cultural value compared to minimally processed food. OBJECTIVE: The objective of this study was to evaluate the effect on growth, metabolism, physical activity (PA), memory, inflammation, and toxicity of an enriched black corn chip (BC) made with endemic ingredients on post-weaned UN mice. METHODS: A chip was made with a mixture of black corn, fava beans, amaranth, and nopal cactus. To probe the effects of UN, UN was induced in 3wo post-weaned male C57Bl/6j mice through a low-protein diet (LPD-50% of the regular requirement of protein) for 3w. Then, the BC was introduced to the animals' diet (17%) for 5w; murinometric parameters were measured, as were postprandial glucose response, PA, and short-term memory. Histological analysis was conducted on the liver and kidneys to measure toxicity. Gene expression related to energy balance, thermogenesis, and inflammation was measured in adipose and hypothalamic tissues. RESULTS: Treatment with the BC significantly improved mouse growth, even with a low protein intake, as evidenced by a significant increase in body weight, tail length, cerebral growth, memory improvement, physical activation, normalized energy expenditure (thermogenesis), and orexigenic peptides (AGRP and NPY). It decreased anorexigenic peptides (POMC), and there was no tissue toxicity. CONCLUSIONS: BC treatment, even with persistent low protein intake, is a promising strategy against UN, as it showed efficacy in correcting growth deficiency, cognitive impairment, and metabolic problems linked to treatment by adjusting energy expenditure, which led to the promotion of energy intake and regulation of thermogenesis, all by using low-cost, accessible, and endemic ingredients.
Assuntos
Modelos Animais de Doenças , Desnutrição , Camundongos Endogâmicos C57BL , Zea mays , Animais , Masculino , Camundongos , Metabolismo Energético , Dieta com Restrição de Proteínas , Fígado/metabolismo , Alimentos Fortificados , TermogêneseRESUMO
INTRODUCTION: Obesity, characterized by excess adipose tissue, is a major public health problem worldwide. Brown adipose tissue (BAT) and beige adipose tissue participate in thermogenesis through uncoupling protein 1 (UCP1). Polyphenols including those from Calafate (a native polyphenol-rich Patagonian berry), are considered as potential anti-obesity compounds due to their pro-thermogenic characteristics. However, polyphenols are mainly metabolized by the gut microbiota (GM) that may influence their bioactivity and bioavailability. The aim of this study was to determine the impact of dietary administration with a Calafate polyphenol-rich extract on thermogenic activity of BAT and beige adipose tissue and GM composition. METHODS: Eight-week-old C57BL6 mice (n = 30) were divided into 4 groups to receive for 24 weeks a control diet (C), a high-fat diet alone (HF), or high-fat diet supplemented with Calafate extract (HFC) or the same high-fat diet supplemented with Calafate extract but treated with antibiotics (HFCAB) from week 19-20. Administration with Calafate extract (50 mg/kg per day) was carried out for 3 weeks from week 21-23 in the HFC and HFCAB groups. After euthanasia, gene expression of thermogenic markers was analyzed in BAT and inguinal white adipose tissue (iWAT). Transmission electron microscopy was performed to assess mitochondrial morphology and cristae density in BAT. GM diversity and composition were characterized by deep sequencing with the MiSeq Illumina platform. RESULTS: Calafate extract administration had no effect on weight gain in mice fed a high-fat diet. However, it prevented alterations in mitochondrial cristae induced by HFD and increased Dio2 expression in BAT and iWAT. The intervention also influenced the GM composition, preventing changes in specific bacterial taxa induced by the high-fat diet. However, the antibiotic treatment prevented in part these effects, suggesting the implications of GM. CONCLUSION: These results suggest that the acute administration of a Calafate extract modulates the expression of thermogenic markers, prevents alterations in mitochondrial cristae and intestinal microbiota in preclinical models. The study highlights the complex interaction between polyphenols, thermogenesis, and the GM, providing valuable insights into their potential roles in the treatment of obesity-related metabolic diseases.
Assuntos
Tecido Adiposo Marrom , Dieta Hiperlipídica , Microbioma Gastrointestinal , Camundongos Endogâmicos C57BL , Extratos Vegetais , Termogênese , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Termogênese/efeitos dos fármacos , Camundongos , Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Marrom/metabolismo , Extratos Vegetais/farmacologia , Masculino , Obesidade/metabolismo , Proteína Desacopladora 1/metabolismo , Tecido Adiposo Bege/efeitos dos fármacos , Tecido Adiposo Bege/metabolismo , Tecido Adiposo Branco/efeitos dos fármacos , Tecido Adiposo Branco/metabolismo , BiomarcadoresRESUMO
Menopause causes important bodily and metabolic changes, which favor the increased occurrence of cardiovascular diseases, obesity, diabetes, and osteoporosis. Resveratrol exerts proven effects on body metabolism, improving glucose and lipid homeostasis and reducing inflammation and oxidative stress in various organs and tissues. Accordingly, this study evaluates the effects of resveratrol supplementation on the expression of markers associated with thermogenesis in brown adipose tissue, and on the body, metabolic and hormonal parameters of female mice submitted to bilateral oophorectomy. Eighteen female mice were randomized into three groups: G1: control (CONTROL), G2: oophorectomy (OOF), and G3: oophorectomy + resveratrol (OOF + RSV); the animals were kept under treatment for twelve weeks, being fed a standard diet and treated with resveratrol via gavage. Body, biochemical, hormonal, and histological parameters were measured; in addition to the expression of markers associated with thermogenesis in brown adipose tissue. The results showed that animals supplemented with resveratrol showed reduced body weight and visceral adiposity, in addition to glucose, total cholesterol, and triglyceride levels; decreased serum FSH levels and increased estrogen levels were observed compared to the OOF group and mRNA expression of PRDM16, UCP1, and SIRT3 in brown adipose tissue. The findings of this study suggest the important role of resveratrol in terms of improving body, metabolic, and hormonal parameters, as well as modulating markers associated with thermogenesis in brown adipose tissue of female mice submitted to oophorectomy.
Assuntos
Tecido Adiposo Marrom , Suplementos Nutricionais , Ovariectomia , Resveratrol , Termogênese , Proteína Desacopladora 1 , Animais , Resveratrol/farmacologia , Resveratrol/administração & dosagem , Feminino , Termogênese/efeitos dos fármacos , Termogênese/genética , Camundongos , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Marrom/efeitos dos fármacos , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismo , Administração Oral , Regulação da Expressão Gênica/efeitos dos fármacos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Sirtuína 3/genética , Sirtuína 3/metabolismo , Peso Corporal/efeitos dos fármacos , Hormônios/sangueRESUMO
AIM: In cyclic climate variations, including seasonal changes, many animals regulate their energy demands to overcome critical transitory moments, restricting their high-demand activities to phases of resource abundance, enabling rapid growth and reproduction. Tegu lizards (Salvator merianae) are ectotherms with a robust annual cycle, being active during summer, hibernating during winter, and presenting a remarkable endothermy during reproduction in spring. Here, we evaluated whether changes in mitochondrial respiratory physiology in skeletal muscle could serve as a mechanism for the increased thermogenesis observed during the tegu's reproductive endothermy. METHODS: We performed high-resolution respirometry and calorimetry in permeabilized red and white muscle fibers, sampled during summer (activity) and spring (high activity and reproduction), in association with citrate synthase measurements. RESULTS: During spring, the muscle fibers exhibited increased oxidative phosphorylation. They also enhanced uncoupled respiration and heat production via adenine nucleotide translocase (ANT), but not via uncoupling proteins (UCP). Citrate synthase activity was higher during the spring, suggesting greater mitochondrial density compared to the summer. These findings were consistent across both sexes and muscle types (red and white). CONCLUSION: The current results highlight potential cellular thermogenic mechanisms in an ectothermic reptile that contribute to transient endothermy. Our study indicates that the unique feature of transitioning to endothermy through nonshivering thermogenesis during the reproductive phase may be facilitated by higher mitochondrial density, function, and uncoupling within the skeletal muscle. This knowledge contributes significant elements to the broader picture of models for the evolution of endothermy, particularly in relation to the enhancement of aerobic capacity.
Assuntos
Lagartos , Músculo Esquelético , Reprodução , Animais , Lagartos/fisiologia , Lagartos/metabolismo , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiologia , Reprodução/fisiologia , Termogênese/fisiologia , Feminino , Masculino , Estações do Ano , Mitocôndrias Musculares/metabolismo , Metabolismo Energético/fisiologiaRESUMO
White adipose tissue (WAT) regulates energy balance through energy storage, adipokines secretion and the thermogenesis process. Beige adipocytes are responsible for WAT thermogenesis. They are generated by adipogenesis or transdifferentiation during cold or ß3-adrenergic agonist stimulus through a process called browning. Browning has gained significant interest for to its preventive effect on obesity. Glucocorticoids (GCs) have several functions in WAT biology; however, their role in beige adipocyte generation and WAT browning is not fully understood. The aim of our study was to determine the effect of dexamethasone (DXM) on WAT thermogenesis. For this purpose, rats were treated with DXM at room temperature (RT) or cold conditions to determine different thermogenic markers. Furthermore, the effects of DXM on the adipogenic potential of beige precursors and on mature beige adipocytes were evaluated in vitro. Our results showed that DXM decreased UCP-1 mRNA and protein levels, mainly after cold exposure. In vitro studies showed that DXM decreased the expression of a beige precursor marker (Ebf2), affecting their ability to differentiate into beige adipocytes, and inhibited the thermogenic response of mature beige adipocytes (Ucp-1, Dio2 and Pgc1α gene expressions and mitochondrial respiration). Overall, our data strongly suggest that DXM can inhibit the thermogenic program of both retroperitoneal and inguinal WAT depots, an effect that could be exerted, at least partially, by inhibiting de novo cell generation and the thermogenic response in beige adipocytes.
Assuntos
Tecido Adiposo Marrom , Tecido Adiposo Branco , Ratos , Animais , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Obesidade/metabolismo , Adipogenia , Dexametasona/farmacologia , TermogêneseRESUMO
Spexin (SPX) is a novel adipokine that plays an emerging role in metabolic diseases due to its involvement in carbohydrate homeostasis, weight loss, appetite control, and gastrointestinal movement, among others. In obese patients, SPX plasma levels are reduced. Little is known about the relationship between SPX and white adipose tissue (WAT) thermogenesis. Therefore, the aim of the present study was to evaluate the role of SPX in this process. C57BL/6J male mice were treated or not with SPX for ten days. On day 3, mice were randomly divided into two groups: one kept at room temperature and the other kept at cold temperature (4 °C). Caloric intake and body weight were recorded daily. At the end of the protocol, plasma, abdominal (epididymal), subcutaneous (inguinal), and brown AT (EAT, IAT, and BAT, respectively) depots were collected for measurements. We found that SPX treatment reduced Uncoupling protein 1 levels in WAT under both basal and cold conditions. SPX also reduced cox8b and pgc1α mRNA levels and mitochondrial DNA, principally in IAT. SPX did not modulate the number of beige precursors. SPX decreased spx levels in IAT depots and galr2 in WAT depots. No differences were observed in the BAT depots. In conclusion, we showed, for the first time, that SPX treatment in vivo reduced the thermogenic process in subcutaneous and abdominal AT, being more evident under cold stimulation.
Assuntos
Tecido Adiposo Marrom , Temperatura Baixa , Hormônios Peptídicos , Termogênese , Animais , Humanos , Masculino , Camundongos , Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Marrom/fisiologia , Tecido Adiposo Branco/metabolismo , Camundongos Endogâmicos C57BL , Termogênese/efeitos dos fármacos , Termogênese/fisiologia , Proteína Desacopladora 1/metabolismo , Hormônios Peptídicos/farmacologia , Hormônios Peptídicos/fisiologiaRESUMO
The discovery of metabolically active brown adipose tissue (BAT) in human adults and the worldwide increase in obesity and obesity-related chronic noncommunicable diseases (NCDs) has made BAT a therapeutic target in the last two decades. The potential of BAT to oxidize fatty acids rapidly and increase energy expenditure inversely correlates with adiposity, insulin and glucose resistance, and cardiovascular and metabolic diseases. Currently, BAT is recognized by a new molecular signature; several BAT-derived molecules that act positively on target tissues have been identified and collectively called batokines. Bioactive compounds present in foods are endowed with thermogenic properties that increase BAT activation signaling. Understanding the mechanisms that lead to BAT activation and the batokines secreted by it within the thermogenic state is fundamental for its recruitment and management of obesity and NCDs. This review contributes to recent updates on the morphophysiology of BAT, its endocrine role in obesity, and the main bioactive compounds present in foods involved in classical and nonclassical thermogenic pathways activation.
Assuntos
Tecido Adiposo Marrom , Obesidade , Humanos , Tecido Adiposo Marrom/metabolismo , Obesidade/metabolismo , Metabolismo Energético , Glucose/metabolismo , Transdução de Sinais , Termogênese , Adipócitos Marrons/metabolismoRESUMO
Perfluorooctanoic acid (PFOA) is a synthetic organofluoride surfactant associated with several toxic effects in humans and animals. Particularly, it has been observed that PFOA treatment of mice results in weight loss associated with recruited brown adipose tissue (BAT), including an increased amount of uncoupling protein 1 (UCP1). The molecular mechanism behind this BAT recruitment is presently unknown. To investigate the existence of possible cell-autonomous effects of PFOA, we treated primary cultures of brown and white (inguinal) adipocytes with PFOA, or with the non-fluorinated equivalent octanoate, or with vehicle, for 48 h (from day 5 to day 7 of differentiation). PFOA in itself increased the gene expression (mRNA levels) of UCP1 and carnitine palmitoyltransferase 1A (CPT1α) (thermogenesis-related genes) in both brown and white adipocytes. In addition, PFOA increased the expression of fatty acid binding protein 4 (FABP4) and peroxisome proliferator-activated receptor α (PPARα) (adipogenesis-related genes). Also the protein levels of UCP1 were increased in brown adipocytes exposed to PFOA. This increase was more due to an increase in the fraction of cells that expressed UCP1 than to an increase in UCP1 levels per cell. The PFOA-induced changes were even more pronounced under simultaneous adrenergic stimulation. Octanoate induced less pronounced effects on adipocytes than did PFOA. Thus, PFOA in itself increased the levels of thermogenic markers in brown and white adipocytes. This could enhance the energy metabolism of animals (and humans) exposed to the compound, resulting in a negative energy balance, leading to diminished fitness.