The effects of mirabegron on obesity-induced inflammation and insulin resistance are associated with brown adipose tissue activation but not beiging in the subcutaneous white adipose tissue.

Mirabegron is a selective ß3-adrenergic receptors agonist, which has been recently shown to improve metabolic health in rodents and humans. In this study, we investigated the effects of 2-week mirabegron treatment on the metabolic parameters of mice with a diet-induced obesity (DIO). C57BL/6JUnib mice were divided into control (CTR) and obese (OB) groups treated with vehicle, and an OB group treated with mirabegron (OB + MIRA). The obese groups were fed a high-fat diet for 12 weeks. Mirabegron (10 mg/kg/day) was administrated orally by gavage from weeks 10-12. After 2 weeks of mirabegron treatment, the energy expenditure was assessed with indirect calorimetry. Blood glucose, insulin, glycerol, free fatty acids (FFA), thiobarbituric acid reactive substance (TBAR), and tumour necrosis factor (TNF)-α levels were also assessed, and the HOMA index was determined. Liver tissue, brown adipose tissue (BAT), and inguinal white adipose tissue (iWAT) samples were collected for histological examination. The protein expressions of uncoupling protein 1 (UCP1) and mitochondrial transcription factor A (TFAM) were assessed using western blotting of the BAT and iWAT samples. In this study, mirabegron increased the energy expenditure and decreased adiposity in OB + MIRA. Increased UCP1 expression in BAT without changes in iWAT was also found. Mirabegron decreased circulating levels of FFA, glycerol, insulin, TNF-α, TBARS and HOMA index. DIO significantly increased the lipid deposits in the liver and BAT, but mirabegron partially reversed this change. Our findings indicate that treatment with mirabegron decreased inflammation and improved metabolism in obese mice. This effect was associated with increased BAT-mediated energy expenditure, but not iWAT beiging, which suggests that mirabegron might be useful for the treatment of obesity and diabetes.

Identification of Suitable Reference Genes for Quantitative Gene Expression Analysis in Innervated and Denervated Adipose Tissue from Cafeteria Diet-Fed Rats.

Our previous studies show that cafeteria diet increases body adiposity, plasma insulin levels, and sympathetic activity to brown adipose tissue (BAT) and white adipose tissue (WAT) of Wistar rats, leading to rapid and progressive changes in the metabolic profile. The identification of suitable reference genes that are not affected by the experimental conditions is a critical step in accurate normalization of the reverse transcription quantitative real-time PCR (qRT-PCR), a commonly used assay to elucidate changes in the gene expression profile. In the present study, the effects of the cafeteria diet and sympathetic innervation on the gene expression of adrenoceptor beta 3 (Adrb3) from BAT and WAT were assessed using one of the most stable and one of the least stable genes as normalizers. Rats were fed the cafeteria diet and on the 17th day, interscapular BAT or retroperitoneal WAT was denervated and, 7 days after surgery, the contralateral innervated tissue was used as control. Ten reference genes were evaluated (18S, B2m, Actb, CypA, Gapdh, Hprt1, Rpl32, Tbp, Ubc, and Ywhaz) and ranked according to their stability using the following algorithms: geNorm, NormFinder, BestKeeper, and comparative delta threshold cycle (ΔC t ) method. According to the algorithms employed, the normalization of Adrb3 expression by the least stable genes produced opposite results compared with the most stable genes and literature data. In cafeteria and control diet-fed rats, the three most stable genes were Hprt1, Tbp, and Rpl32 for interscapular BAT and Tbp, B2m, and Hprt1 for retroperitoneal WAT, while the least stable genes were 18S, Actb, and Gapdh for both tissues.

Chia oil supplementation changes body composition and activates insulin signaling cascade in skeletal muscle tissue of obese animals.

OBJECTIVE: Chia seed oil is the richest source of plant-based ω-3 fatty acid, α-linolenic acid, but its potential and mechanisms of action to treat obesity are unclear. The aim of the study was to evaluate the effects of chia oil (ChOi) supplementation on body composition and insulin signaling in skeletal muscles of obese mice. METHODS: Male C57 BL/6 mice (n = 8/group) were fed regular control chow or a high-fat diet (HFD) for 135 d. Another HFD group additionally received ChOi from 90 to 135 d. RESULTS: Consumption of ChOi reduced fat mass accumulation and increased lean mass as evidenced by nuclear magnetic resonance. Moreover, obese mice treated with ChOi showed higher tyrosine phosphorylation of insulin receptor substrate 1, greater activation of protein kinase B, and increased translocation of glucose transporter type 4 in skeletal muscle tissue in response to insulin. ChOi supplementation improved glucose levels and insulin tolerance; decreased serum insulin, leptin, and triacylglycerols; and increased blood high-density lipoprotein cholesterol levels. All these effects caused by the use of ChOi seemed to be independent of the resolution of inflammation because the markers of inflammation were not altered in animals fed the HFD. CONCLUSION: The molecular effects observed in muscle tissue together with changes in body composition may have contributed to the increased glucose tolerance and to the healthy phenotype presented by obese animals treated with ChOi.

Increase in liver cytosolic lipases activities and VLDL-TAG secretion rate do not prevent the non-alcoholic fatty liver disease in cafeteria diet-fed rats.

We have previously shown that the cafeteria diet increases body fat mass, plasma triacylglycerol (TAG) and insulin levels, glucose uptake by white and brown adipose tissues, as well as the sympathetic activity to both adipose tissues in Wistar rats. The metabolic pathways responsible for the development of non-alcoholic fatty liver disease (NAFLD) were examined in cafeteria diet-fed rats. After 3 weeks offering cafeteria diet, we evaluated: (i) activity of the sympathetic nervous system by norepinephrine turnover rates; (ii) de novo fatty acid synthesis in vivo using 3H2O; (iii) secretion of very low density lipoprotein (VLDL)-TAG secretion measuring serum TAG levels after administration of lipase lipoprotein inhibitor, (iv) liver cytosolic lipases activities and (v) liver mRNA expression of enzymes involved in lipids secretion and oxidation by RT-PCR. The cafeteria diet induced an increase in TAG (120%) and cholesterol (30%) liver contents. Cafeteria diet did not change the sympathetic nervous system activity to liver, but induced a marked increase in the lipogenesis (approximately four-fold) and significant increase in cytosolic lipases activities (46%) and VLDL-TAG secretion (22%) compared to control diet-fed rats. The cafeteria diet also increased the microsomal triglyceride transfer protein (30%) and carnitine palmitoyltransferase I (130%) mRNA expression but decreased the apolipoprotein B100 (26%) mRNA expression. Our findings demonstrate that the increase in the cytosolic lipases activities and VLDL-TAG secretion rates were not able to compensate for the increased lipogenesis rates induced by the cafeteria diet, resulting in NAFLD.

Taioba (Xanthosoma sagittifolium) leaves: nutrient composition and physiological effects on healthy rats.

Several studies have shown that fruits and vegetables contribute to protect against degenerative pathologies such as cardiovascular diseases, diabetes, and cancer, mainly due to the presence of dietary fiber (DF) and polyphenols. Taioba (Xanthosoma sagittifolium) is an edible aroid widely grown in many parts of Africa, America, and Asia. The tubers portions of taioba are widely consumed; however, the leafy portions are generally discarded, despite their high nutritive value. In this study, we have partly characterized the DF of lyophiized taioba leaf (LTL), and assessed the possible protective effects on biochemical parameters and on bile acid (BA) production in colon and cecum, when fed to healthy rats for 4 wk. Forty-five Wistar rats were assigned to either of 5 groups: group 1 received AIN 93G diet (CG: Control); group 2 received AIN 93G containing 2.5% of cellulose + 2.5% inulin (CEIN_5%); group 3 received AIN 93G containing 2.5% of cellulose + 2.5% taioba fiber (CETA_5%); group 4 received AIN 93G containing 5% cellulose + 2.5% taioba fiber (CETA_7.5%); group 5 received AIN 93G containing 5% cellulose + 2.5% of inulin (CEIN_7.5%). LTL showed high contents of total fiber, predominantly comprising insoluble DF with glucose as the major monomer. Rats receiving LTL had increased fecal mass and fat excretion, and improved BA profiles by diminishing the proportion of secondary acids, thus suggesting that consumption of taioba leaf may have the property of lowering the risk of colon cancer.

A soyabean diet does not modify the activity of brown adipose tissue but alters the rate of lipolysis in the retroperitoneal white adipose tissue of male rats recovering from early-life malnutrition.

Nutritional recovery with a soyabean diet decreases body and fat weights when compared with a casein diet. We investigated whether the reduced adiposity observed in rats recovering from early-life malnutrition with a soyabean diet results from alterations in lipid metabolism in white adipose tissue (WAT) and/or brown adipose tissue (BAT). Male rats from mothers fed either 17 or 6 % protein during pregnancy and lactation were maintained on 17 % casein (CC and LC groups), 17 % soyabean (CS and LS groups) or 6 % casein (LL group) diets over 60 d. The rats maintained on a soyabean diet had similar relative food intakes, but lower body and retroperitoneal WAT weights and a reduced lipid content in the retroperitoneal WAT. The insulin levels were lower in the recovered rats and were elevated in those fed a soyabean diet. Serum T3 concentration and uncoupling protein 1 content in the BAT were decreased in the recovered rats. The thermogenic capacity of the BAT was not affected by the soyabean diet. The lipogenesis rate in the retroperitoneal WAT was similar in all of the groups except for the LL group, which had exacerbated lipogenesis. The enhancement of the lipolysis rate by isoproterenol was decreased in white adipocytes from the soyabean-recovered rats and was elevated in adipocytes from the soyabean-control rats. Thus, in animals maintained on a soyabean diet, the proportions of fat deposits are determined by the lipolysis rate, which differs depending on the previous nutritional status.

Efeito dos ácidos graxos n-3 e n-6 na expressão de genes do metabolismo de lipídeos e risco de aterosclerose / Effects of n-3 and n-6 fatty acids on the expression of genes involved in the lipid metabolism and risk of atherosclerosis

A aterosclerose, principal responsável pela patogênese do infarto miocárdico e cerebral, bem como pela gangrena e por outras doenças vasculares periféricas, permanece como principal causa de morbidade e mortalidade nas populações "ocidentalizadas". Estima-se que 17,5 milhões de pessoas morreram por doenças cardiovasculares em 2005, o que representou 30 por cento das causas de morte nesse ano, e que, em 2015, 20 milhões de pessoas morrerão por doenças cardiovasculares no mundo. Os ácidos graxos n-3, principalmente os de cadeia longa, encontrados nos peixes, têm-se mostrado particularmente úteis na prevenção e tratamento de doenças como dislipidemias, diabetes mellitus e obesidade, apresentando importante efeito cardioprotetor. Nesse contexto, pesquisas têm evidenciado que ao menos parte dos benefícios dos ácidos graxos eicosapentaenóico e docosahexaenóico sobre o risco de doenças cardiovasculares é decorrente da modulação de genes responsivos aos receptores ativados por proliferadores de peroxissomos e envolvidos no metabolismo lipídico. Nesta revisão, pretende-se expor alguns mecanismos de ação dos ácidos graxos n-3 e n-6 sobre o metabolismo de lipídeos e de lipoproteínas. Conclui-se que muitos aspectos que contribuem para o risco de doenças cardiovasculares são afetados pela ingestão de n-3. Além da redução de triglicérides, fatores como o aumento de adiponectina, a redução da concentração de colesterol plasmático e a melhora do transporte reverso de colesterol também são responsáveis pela redução do risco de aterosclerose promovida pelos ácidos graxos n-3. No entanto, ainda são necessários estudos adicionais para definir mais claramente os mecanismos celulares e moleculares responsáveis pelo efeito cardioprotetor dos ácidos graxos n-3.

Atherosclerosis, the main cause of myocardial infarction, stroke, gangrene and other peripheral vascular diseases, also persists as the main cause of morbidity and mortality in Western populations. Roughly 17.5 million people died from cardiovascular diseases in 2005, representing 30 percent of the causes of death in that year, and in 2015, another 20 million people will die of cardiovascular diseases around the world. The n-3 fatty acids, especially the long-chain n-3 found in fish, have been shown to be particularly effective in the prevention and treatment of diseases such as dyslipidemias, diabetes mellitus and obesity, presenting an important cardioprotective effect. In this context, studies have found that at least some of the cardiovascular benefits associated with eicosapentaenoic and docosahexaenoic fatty acids regard the modulation of genes that respond to the peroxisome proliferator-activated receptors involved in lipid metabolism. This review will discuss some of the mechanisms of action of some n-3 and n-6 fatty acids on the metabolism of lipids and lipoproteins. In conclusion, many aspects that contribute to the risk of cardiovascular diseases are affected by n-3 intake. N-3 fatty acids not only reduce triglycerides, but also promote factors that increase adiponectin, reduce blood cholesterol levels and improve the reverse cholesterol transport, and all of these contribute to reducing the risk of atherosclerosis. However, additional studies are still necessary to elucidate all the cellular and molecular mechanisms responsible for the cardioprotective effect of n-3 fatty acids.

Restrição alimentar de carboidratos no tratamento da obesidade / Restricted carbohydrate intake in obesity treatment

Alteração nos padrões alimentares associados ao aumento do sedentarismo têm sido relacionadas com a epidemia da obesidade, doença que envolve interação complexa entre fatores genéticos e metabólicos entre outros. O excesso de peso está associado ao risco de doença aterosclerótica, diabetes mellitus tipo 2 e certos tipos de cânceres, além de provocar efeitos adversos no metabolismo, como aumento da pressão arterial, dislipidemias e resistência à insulina. No tratamento da obesidade é importante considerar todos os fatores causais, sendo indicada atuação multidisciplinar. É recomendada mudança no estilo de vida, mas, em alguns casos, são necessários medicamentos ou mesmo intervenção cirúrgica. Dentre as intervenções nutricionais, as dietas com restrição de carboidratos têm se tornado cada vez mais populares. Este trabalho buscou apresentar os principais resultados de estudos dos últimos dez anos referentes a dietas restritas em carboidratos como parte do tratamento da obesidade. Os estudos mostram-se bastante heterogêneos, dificultando a comparação entre eles. A perda de peso parece estar mais relacionada à restrição energética, responsável por balanço energético negativo do que com o conteúdo de carboidrato das dietas. Embora alguns autores relatem melhora do perfil lipídico, da glicemia e da insulinemia, relacionada às dietas restritas em carboidratos, ainda estamos distantes de um consenso. Conclui-se, portanto, que ainda não há evidências suficientes para recomendações de tais dietas.

Adaptação das diretrizes alimentares para a população brasileira e o estabelecimento do índice de alimentação saudável para pré-escolares de 2 a 6 anos / Adaptation of the dietary guidelines for brazilian population and the application of the healthy eating index for preschool aged between 2 and 6 years

Guias Alimentares podem ser úteis para o monitoramento do padrão alimentar e para o conhecimento do risco de comprometimento do estado nutricional de grupos populacionais. O Healthy Eating Index – HEI é o resultado de um método para avaliação da qualidade da dieta que compara o padrão dietético norte americano com as recomendações estabelecidas na Pirâmide Alimentar desenvolvida para aquela população. A Agência Nacional de Vigilância Sanitária estabeleceu as Diretrizes Alimentares para População Brasileira - DAPBs, visando definir porções de alimentos e bebidas com o objetivo de orientar a rotulagem de produtos alimentares. Ainda não se conhece estudo de avaliação das DAPBs, e não há um sistema de avaliação qualitativa do consumo alimentar de grupos populacionais. Este trabalho avaliou a aplicação do HEI para uso no Brasil, empregando-se como referência as DAPBs, visando gerar indicadores na forma de um Índice de Alimentação Saudável - IAS. Para o estudo de adaptação, foram empregados os dados de consumo de 94 pré-escolares de 2 a 6 anos, por meio de pesagem direta dos alimentos consumidos na creche, combinada com o recordatório 24h. A aplicação do IAS mostrou baixo consumo de cereais, verduras e legumes; excesso no consumo de leguminosas, carnes, ovos, laticínios, gordura saturada e açúcares; o consumo de óleos e gorduras pareceu estar dentro do esperado. O IAS pode ser utilizado para monitorar o consumo, auxiliando no diagnóstico e avaliação de insegurança alimentar, mas a aplicação das DAPBs não é adequada para a categorização dos alimentos em porções por grupos alimentares