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Omega 3 (ω3) fatty acids have been described since the 1980s as promising anti-inflammatory substances. Prostaglandin and leukotriene modulation were exhaustively explored as the main reason for ω3 beneficial outcomes. However, during the early 2000s, after the human genome decoding advent, the nutrigenomic approaches exhibited an impressive plethora of ω3 targets, now under the molecular point of view. Different G protein-coupled receptors (GPCRs) recognizing ω3 and its derivatives appear to be responsible for blocking inflammation and insulin-sensitizing effects. A new class of ω3-derived substances, such as maresins, resolvins, and protectins, increases ω3 actions. Inflammasome disruption, the presence of GPR120 on immune cell surfaces, and intracellular crosstalk signaling mediated by PPARγ compose the last discoveries regarding the multipoint anti-inflammatory targets for this nutrient. This review shows a detailed mechanistic proposal to understand ω3 fatty acid action over the inflammatory environment in the background of several chronic diseases. [ABSTRACT FROM AUTHOR]

The hypothalamus plays a critical role in the control of food consumption and energy expenditure. Fatty diets can elicit an inflammatory response in specific hypothalamic cells, including astrocytes, tanycytes, and microglia, disrupting anorexigenic signals in region-specific hypothalamic neurons, contributing to overeating and body weight gain. In this study, we present an update regarding the knowledge of the effects of physical exercise on inflammatory signaling and circuits to control hunger in the hypothalamus in obesity conditions. To try to understand changes in the hypothalamus, we review the use of magnetic resonance/anorexigenic hormone analysis in humans, as well as in animal models to explore the physiological and molecular mechanism by which exercise modulates satiety signals, such as the central antiinflammatory response, myokine delivery from skeletal muscle, and others. The accumulation of scientific evidence in recent years allows us to understand that exercise contributes to weight control, and it is managed by mechanisms that go far beyond "burning calories.". [ABSTRACT FROM AUTHOR]

Autophagy plays an essential role in body homeostasis achievement. One of the main proteins involved in this process is the LC3I, which, after lipidation, leads to the formation of LC3II that participates in the formation and maturation of autophagosome. This descriptive study verified the responses of LC3II to LC3I proteins, as well as the time-course of this ratio in mice livers after different types of acute physical exercise protocols. Eight-week-old male C57BL/6 mice were maintained three per cage with controlled temperature (22±2 °C) on a 12:12-h light-dark normal cycle with food (Purina chow) and water ad libitum. Mice were randomly divided into four groups: control (CT, sedentary mice), resistance (RE, submitted to a single bout of resistance exercise), endurance (EE, submitted to a single bout of endurance exercise), and concurrent (CE, submitted to a single bout of endurance combined with resistance exercise). The mice livers were extracted and used for the immunoblotting technique. The hepatic LC3B II/I ratio for the RE and EE groups were not altered during the different time-points. For the CE group, there was a decrease in this ratio 12h after exercise compared to time 0 and 18h. Also, the hepatic LC3B II/I ratios were not different among the acute physical exercise protocols along the time-course. The hepatic LC3B II/I ratio was not influenced by the endurance and resistance protocols but decreased in response to the concurrent protocol at 12h after the stimulus. [ABSTRACT FROM AUTHOR]

Fructose consumption has been growing exponentially and, concomitant with this, the increase in the incidence of obesity and associated complications has followed the same behavior. Studies indicate that fructose may be a carbohydrate with greater obesogenic potential than other sugars. In this context, the liver seems to be a key organ for understanding the deleterious health effects promoted by fructose consumption. Fructose promotes complications in glucose metabolism, accumulation of triacylglycerol in the hepatocytes, and alterations in the lipid profile, which, associated with an inflammatory response and alterations in the redox state, will imply a systemic picture of insulin resistance. However, physical exercise has been indicated for the treatment of several chronic diseases. In this review, we show how each exercise protocol (aerobic, strength, or a combination of both) promote improvements in the obesogenic state created by fructose consumption as an improvement in the serum and liver lipid profile (high-density lipoprotein (HDL) increase and decrease triglyceride (TG) and low-density lipoprotein (LDL) levels) and a reduction of markers of inflammation caused by an excess of fructose. Therefore, it is concluded that the practice of aerobic physical exercise, strength training, or a combination of both is essential for attenuating the complications developed by the consumption of fructose. [ABSTRACT FROM AUTHOR]

To maintain euglycemia in healthy organisms, hepatic glucose production is increased during fasting and decreased during the postprandial period. This whole process is supported by insulin levels. These responses are associated with the insulin signaling pathway and the reduction in the activity of key gluconeogenic enzymes, resulting in a decrease of hepatic glucose production. On the other hand, defects in the liver insulin signaling pathway might promote inadequate suppression of gluconeogenesis, leading to hyperglycemia during fasting and after meals. The hepatocyte nuclear factor 4, the transcription cofactor PGC1-α, and the transcription factor Foxo1 have fundamental roles in regulating gluconeogenesis. The loss of insulin action is associated with the production of pro-inflammatory biomolecules in obesity conditions. Among the molecular mechanisms involved, we emphasize in this review the participation of TRB3 protein (a mammalian homolog of Drosophila tribbles), which is able to inhibit Akt activity and, thereby, maintain Foxo1 activity in the nucleus of hepatocytes, inducing hyperglycemia. In contrast, physical exercise has been shown as an important tool to reduce insulin resistance in the liver by reducing the inflammatory process, including the inhibition of TRB3 and, therefore, suppressing gluconeogenesis. The understanding of these new mechanisms by which physical exercise regulates glucose homeostasis has critical importance for the understanding and prevention of diabetes. [ABSTRACT FROM AUTHOR]

Since diabetes mellitus is considered a world public health problem, the present study aimed to evaluate oral glucose tolerance (TTGo) and pancreatic insulin concentration (PIC) of type I diabetic rats subjected to an individualized exercise training protocol. A total of 40 adult Wistar rats were used, half of which induced to diabetes by alloxan (32 mg/kg) endovenous injection, and divided into four groups (10 per group): Sedentary Control (SC), Trained Control (TC), Sedentary Diabetic (SD) and Trained Diabetic (TD). The physical training consisted of swimming, 1 h/day, 5 days/week during 8 weeks, supporting overload equivalent to 90% of the individual anaerobic/aerobic metabolic transition determined at the beginning of the experiment. The rats of SD and TD groups presented body weight reduction in relation to controls, which was less accentuated in TD group. Water and food ingestion increased in the diabetic groups in relation to controls. The areas under the serum glucose curve during the GTTo of diabetic groups were higher than the controls. Physical training attenuated this elevation. The diabetic groups showed reduced PIC when compared to both control groups. The physical training protocol employed improved glucose homeostasis and attenuated the body weight loss of diabetic animals but did not alter pancreatic insulin concentration. [ABSTRACT FROM AUTHOR]

Introdução. Ácidos graxos ômega-3 (ω3) são encontrados principalmente em óleos de peixe, e sua suplementação tem sido empregada no auxílio ao tratamento e prevenção de doenças cardiovasculares, se ingeridos em doses adequadas. Entretanto, devido à relevância que que vem ganhando no mercado de produtos saudáveis, tanto no Brasil quanto no mundo, os casos de adulteração do conteúdo do óleo das cápsulas tem sido registrados com frequência. O objetivo do estudo foi analisar o perfil de ácidos graxos nas principais marcas de ω3 comercializadas no mercado brasileiro. Métodos. Inicialmente foram selecionados e adquiridos quatorze marcas de suplementos de ω3, comercializados em todos os estados do Brasil, com grande visibilidade midiática. Para análise do perfil de ácidos graxos das cápsulas, o conteúdo do óleo foi extraído e submetido ao processo saponificação e esterificação. Posteriormente, utilizou-se um cromatógrafo a gás, acoplado a um espectrômetro de massas. Houve diferença entre a quantidade de ácidos graxos impresso nos rótulos e a encontrada na análise, no tocante ao total de gorduras saturadas, monoinsaturadas, poliinsaturadas, e também ácido eicosapentaenóico (EPA) e docosahexaenoico (DHA). A legislação brasileira admite de ± 20% de variabilidade. Apenas a gordura poli-insaturada obteve adequação maior que 50% nos suplementos analisados. Em contrapartida, gordura saturada e monoinsaturada apresentaram-se inadequadas em 79% das marcas. Foi constatado que ambos o EPA e DHA estavam inadequados em 50% das marcas. Ácidos graxos ω6 apresentaramse em quantidade elevada em um dos produtos. No tocante ao ω3, algumas marcas possuíram quantidade razoável, mas apenas duas atenderam a dosagem mínima de 2 g/porção, quantidade mínima recomendada ao tratamento de hipertrigliceridemia. Os resultados. do presente estudo demonstram que todas as marcas apresentaram incongruências entre a quantidade de nutrientes alegado nos rótulos e o detectado em análise. Apesar do estudo não ter detectado fraudes com misturas de outros óleos nas cápsulas, encontrou produtos com concentrações irrelevantes de ω3. Isso reforça a necessidade de monitoramento da qualidade desses suplementos pelos fabricantes e agências governamentais do país, uma vez que são dispensados, por legislação, de registro no Ministério da Saúde ou Agricultura, a fim de coibir produtos de tão baixa qualidade. [ABSTRACT FROM AUTHOR]

Estudos apontam para a obesidade como um dos principais fatores ambientais predisponentes à Doença de Alzheimer (DA), marcada pelo acúmulo anormal das proteínas beta-amiloide e hiperfosforilação da Tau. Nesse estudo translacional, o objetivo foi avaliar se a substituição parcial da gordura suína (fonte de saturados) por de óleo de linhaça (fonte de ácido ω3 [alfa-linolênico]) pode bloquear vias moleculares associadas à DA, no hipocampo de animais obesos e diabéticos. Também, o perfil de ácidos graxos e marcadores da DA no líquor de pacientes com deficit cognitivo. Camundongos foram alocados nos seguintes grupos: Grupo controle (N=10) - ração comercial por 16 semanas; Obeso (N=10) - dieta hiperlipídica por 16 semanas; Obeso+ω3 (N=10) - que receberam dieta hiperlipídica por 8 semanas e, posteriormente, dieta hiperlipídica substituída em 1/3 da gordura suína por óleo de linhaça, por mais 8 semanas. Os animais foram submetidos aos testes de: tolerância à insulina e glicose, aprendizado e memória. O hipocampo foi coletado para análises: morfológicas (microscopia eletrônica - M.E); proteínas (Western blot) e genes (RT-qPCR) envolvidos na DA, e espectrometria de massas para o perfil de ácidos graxos no sangue e hipocampo. Quarenta pacientes foram submetidos à antropometria e análises do liquor. Nos animais, os obesos apresentaram intolerância à glicose e resistência sistêmica e hipocampal à insulina. No hipocampo, houve aumento na expressão gênica e proteica de marcadores inflamatórios (IL1β, TNFα, p-JNK), de estresse de retículo (p-eIF2α, CHOP), apoptose (BAX) e da DA (βamiloide, p-Tau). Na M.E. observou-se importante neurodegeneração hipocampal nos obesos, justificando o prejuízo cognitivo, comparados ao grupo controle. O grupo que recebeu óleo de linhaça apresentou a molécula de ω3 incorporada nos neurônios hipocampais, e redução significante nos marcadores descritos. Os pacientes apresentaram IL1β e βamiloide aumentadas no liquor, proporcional ao aumento da massa corporal adiposa, associada também à menor presença de ω3. A dieta contendo óleo de linhaça foi eficaz em controlar o estado inflamatório e degenerativo, induzidos pela obesidade, e desacelerou o surgimento da DA ao preservar as funções hipocampais. Em humanos houve correlação dos achados experimentais, mostrando possibilidade terapêutica de uso preventivo de ω3 à Doença de Alzheimer. [ABSTRACT FROM AUTHOR]

Although unfolded protein response (UPR) is essential for cellular protection, its prolonged activation may induce apoptosis, compromising cellular longevity. The aging process increases the endoplasmic reticulum (ER) stress in skeletal muscle. However, whether combined exercise can prevent age-induced ER stress in skeletal muscle remains unknown. Evidence suggests that ER stress may increase inflammation by counteracting the positive effects of interleukin-10 (IL-10), whereas its administration in cells inhibits ER stress and apoptosis. This study verified the effects of aging and combined exercise on physical performance, ER stress markers, and inflammation in the quadriceps of mice. Moreover, we verified the effects of IL-10 on ER stress markers. C57BL/6 mice were distributed into young (Y, 6 mo old), old sedentary (OS, sedentary, 24 mo old), and old trained group (OT, submitted to short-term combined exercise, 24 mo old). To clarify the role of IL-10 in UPR pathways, knockout mice lacking IL-10 were used. The OS mice presented worse physical performance and higher ER stress-related proteins, such as C/EBP homologous protein (CHOP) and phospho-eukaryotic translation initiation factor 2 alpha (p-eIF2α/eIF2α). The exercise protocol increased muscle strength and IL-10 protein levels in OT while inducing the downregulation of CHOP protein levels compared with OS. Furthermore, mice lacking IL-10 increased BiP, CHOP, and p-eIF2α/eIF2α protein levels, indicating this cytokine can regulate the ER stress response in skeletal muscle. Bioinformatics analysis showed that endurance and resistance training downregulated DNA damage inducible transcript 3 (DDIT3) and XBP1 gene expression in the vastus lateralis of older people, reinforcing our findings. Thus, combined exercise is a potential therapeutic intervention for promoting adjustments in ER stress markers in aged skeletal muscle. NEW & NOTEWORTHY Aging elevates endoplasmic reticulum (ER) stress in skeletal muscle, potentially heightening inflammation by opposing interleukin-10 (IL-10) effects. This study found that short-term combined exercise boosted strength and IL-10 protein levels while reducing CHOP protein levels in older mice. In addition, IL-10-deficient mice exhibited increased ER stress markers, highlighting IL-10's role in regulating ER stress in skeletal muscle. Consequently, combined exercise emerges as a therapeutic intervention to elevate IL-10 and adjust ER stress markers in aging.

Nonalcoholic fatty liver disease (NAFLD), a condition characterized by the accumulation of fat in the liver, is estimated to be the most common liver disease worldwide. Obesity is a major risk factor and contributor, and, accordingly, weight loss can improve NAFLD. Previous studies in preclinical models of diet-induced obesity and fatty liver disease have shown the independent benefits of resistance exercise training (RT) and time-restricted feeding (TRF) in preventing weight gain and hepatic build-up of fat. Here, we tested the combined effect of TRF and RT on obesity and NAFLD in mice fed a high-fat diet. Our results showed that both TRF-8-h food access in the active phase-and RT-consisting of three weekly sessions of ladder climbing-attenuated body weight gain, improved glycemic homeostasis, and decreased the accumulation of lipids in the liver. TRF combined with RT improved the respiratory exchange rate, energy expenditure, and mitochondrial respiration in the liver. Furthermore, gene expression analysis in the liver revealed lower mRNA expression of lipogenesis and inflammation genes along with increased mRNA of fatty acid oxidation genes in the TRF + RT group. Importantly, combined TRF + RT was shown to be more efficient in preventing obesity and metabolic disorders. In conclusion, TRF and RT exert complementary actions compared with isolated interventions, with significant effects on metabolic disorders and NAFLD in mice. NEW & NOTEWORTHY Whether time-restricted feeding (TRF) combined with resistance exercise training (RT) may be more efficient compared with these interventions alone is still unclear. We show that when combined with RT, TRF provided additional benefits, being more effective in increasing energy expenditure, preventing weight gain, and regulating glycemic homeostasis than each intervention alone. Thus, our results demonstrate that TRF and RT have complementary actions on some synergistic pathways that prevented obesity and hepatic liver accumulation.