Physical exercise elicits UPR in the skeletal muscle: The role of c-Jun N-terminal kinase.

Objective: The mitochondrial unfolded protein response (UPR) is an adaptive cellular response to stress to ensure mitochondrial proteostasis and function. Here we explore the capacity of physical exercise to induce UPR in the skeletal muscle.

Methods: Therefore, we combined mouse models of exercise (swimming and treadmill running), pharmacological intervention, and bioinformatics analyses.

Exogenous succinate impacts mouse brown adipose tissue mitochondrial proteome and potentiates body mass reduction induced by liraglutide.

Obesity is one of the leading noncommunicable diseases in the world. Despite intense efforts to develop strategies to prevent and treat obesity, its prevalence continues to rise worldwide. A recent study has shown that the tricarboxylic acid intermediate succinate increases body energy expenditure by promoting brown adipose tissue thermogenesis through the activation of uncoupling protein-1; this has generated interest surrounding its potential usefulness as an approach to treat obesity.

FOXO1 is downregulated in obese mice subjected to short-term strength training.

Obesity is a worldwide health problem and is directly associated with insulin resistance and type 2 diabetes. The liver is an important organ for the control of healthy glycemic levels, since insulin resistance in this organ reduces phosphorylation of forkhead box protein 1 (FOXO1) protein, leading to higher hepatic glucose production (HGP) and fasting hyperglycemia. Aerobic physical training is known as an important strategy in increasing the insulin action in the liver by increasing FOXO1 phosphorylation and reducing gluconeogenesis.

Hypothalamic CREB Regulates the Expression of Pomc-Processing Enzyme Pcsk2.

Background: The hypothalamic proopiomelanocortin (Pomc) neurons act as first-order sensors of systemic energy stores, providing signals that regulate caloric intake and energy expenditure. In experimental obesity, dietary saturated fatty acids affect Pomc endopeptidases (PCs), resulting in the abnormal production of the neurotransmitters α-melanocyte-stimulating hormone (α-MSH) and β-endorphin, thus impacting energy balance. The cAMP response element-binding protein (CREB) is one of the transcription factors that control the expression of Pomc endopeptidases; however, it was previously unknown if dietary fats could affect CREB and consequently the expression of Pomc endopeptidases.

Arcuate Nucleus Overexpression of NHLH2 Reduces Body Mass and Attenuates Obesity-Associated Anxiety/Depression-like Behavior.

Nescient helix-loop-helix 2 (NHLH2) is a hypothalamic transcription factor that controls the expression of prohormone convertase 1/3, therefore having an impact on the processing of proopiomelanocortin and thus on energy homeostasis. Studies have shown that KO of results in increased body mass, reduced physical activity, and hypogonadism. In humans, a polymorphism of the gene is associated with obesity; and in Prader-Willi syndrome, a condition characterized by obesity, hypogonadism and behavioral abnormalities, the expression of NHLH2 is reduced.

Interleukin-17 acts in the hypothalamus reducing food intake.

Interleukin-17 (IL-17) is expressed in the intestine in response to changes in the gut microbiome landscape and plays an important role in intestinal and systemic inflammatory diseases. There is evidence that dietary factors can also modify the expression of intestinal IL-17. Here, we hypothesized that, similar to several other gut-produced factors, IL-17 may act in the hypothalamus to modulate food intake.

TGF-β1 downregulation in the hypothalamus of obese mice through acute exercise.

Obesity and aging lead to abnormal transforming growth factor-β1 (TGF-β1) signaling in the hypothalamus, triggering the imbalance on glucose metabolism and energy homeostasis. Here, we determine the effect of acute exercise on TGF-β1 expression in the hypothalamus of two models of obesity in mice. The bioinformatics analysis was performed to evaluate the correlation between hypothalamic Tgf-β1 messenger RNA (mRNA) and genes related to thermogenesis in the brown adipose tissue (BAT) by using a large panel of isogenic BXD mice.

Short-term strength training reduces gluconeogenesis and NAFLD in obese mice.

Non-alcoholic fatty liver disease (NAFLD) has a positive correlation with obesity, insulin resistance and type 2 diabetes mellitus (T2D). The aerobic training is an important tool in combating NAFLD. However, no studies have demonstrated the molecular effects of short-term strength training on the accumulation of hepatic fat in obese mice.

Hypothalamic expression of the atypical chemokine receptor ACKR2 is involved in the systemic regulation of glucose tolerance.

In experimental obesity, the hypothalamus is affected by an inflammatory response activated by dietary saturated fats. This inflammation is triggered as early as one day after exposure to a high-fat diet, and during its progression, there is recruitment of inflammatory cells from the systemic circulation. The objective of the present study was identifying chemokines potentially involved in the development of hypothalamic diet-induced inflammation.

CD1 is involved in diet-induced hypothalamic inflammation in obesity.

Obesity-associated hypothalamic inflammation plays an important role in the development of defective neuronal control of whole body energy balance. Because dietary fats are the main triggers of hypothalamic inflammation, we hypothesized that CD1, a lipid-presenting protein, may be involved in the hypothalamic inflammatory response in obesity. Here, we show that early after the introduction of a high-fat diet, CD1 expressing cells gradually appear in the mediobasal hypothalamus.

The partial inhibition of hypothalamic IRX3 exacerbates obesity.

Background: The Iroquois homeobox 3 (Irx3) gene has been identified as a functional long-range target of obesity-associated variants within the fat mass and obesity-associated protein (FTO) gene. It is highly expressed in the hypothalamus, and both whole-body knockout and hypothalamic restricted abrogation of its expression results in a lean phenotype, which is mostly explained by the resulting increased energy expenditure in the brown adipose tissue. Because of its potential implication in the pathogenesis of obesity, we evaluated the hypothalamic cell distribution of Irx3 and the outcomes of inhibiting its expression in a rodent model of diet-induced obesity.

Abnormal brown adipose tissue mitochondrial structure and function in IL10 deficiency.

Background: Inflammation is the most relevant mechanism linking obesity with insulin-resistance and metabolic disease. It impacts the structure and function of tissues and organs involved in metabolism, such as the liver, pancreatic islets and the hypothalamus. Brown adipose tissue has emerged as an important component of whole body energy homeostasis, controlling caloric expenditure through the regulation of non-shivering thermogenesis.

Exercise activates the hypothalamic S1PR1-STAT3 axis through the central action of interleukin 6 in mice.

Hypothalamic sphingosine-1-phosphate receptor 1 (S1PR1), the G protein-coupled receptor 1 of sphingosine-1-phosphate, has been described as a modulator in the control of energy homeostasis in rodents. However, this mechanism is still unclear. Here, we evaluate the role of interleukin 6 (IL-6) associated with acute physical exercise in the control of the hypothalamic S1PR1-signal transducer and activator of transcription 3 (STAT3) axis.

The role of physical exercise on Sestrin1 and 2 accumulations in the skeletal muscle of mice.

Aims: Sestrins, a class of stress-related proteins, is involved in the control of aging-induced organic dysfunctions and metabolic control. However, the factors that modulate the levels of Sestrins are poorly studied. Here, we evaluated the effects of acute and chronic aerobic exercise on Sestrin 1 (Sesn1) and Sesn2 protein contents in the skeletal muscle of mice.

Physical exercise reduces pyruvate carboxylase (PCB) and contributes to hyperglycemia reduction in obese mice.

The present study evaluated the effects of exercise training on pyruvate carboxylase protein (PCB) levels in hepatic tissue and glucose homeostasis control in obese mice. Swiss mice were distributed into three groups: control mice (CTL), fed a standard rodent chow; diet-induced obesity (DIO), fed an obesity-inducing diet; and a third group, which also received an obesity-inducing diet, but was subjected to an exercise training protocol (DIO + EXE). Protocol training was carried out for 1 h/d, 5 d/wk, for 8 weeks, performed at an intensity of 60% of exhaustion velocity.

Strength Training Prevents Hyperinsulinemia, Insulin Resistance, and Inflammation Independent of Weight Loss in Fructose-Fed Animals.

The aim of this study was to compare the effects of aerobic, strength, and combined training on metabolic disorders induced by a fructose-rich diet. Wistar rats (120 days old) were randomized into five groups (n = 8-14): C (control diet and sedentary), F (fed the fructose-rich diet and sedentary), FA (fed the fructose-rich diet and subject to aerobic exercise), FS (fed the fructose-rich diet and subject to strength exercise), and FAS (fed the fructose-rich diet and subject to combined aerobic and strength exercises). After the 8-week experiment, glucose homeostasis, blood biochemistry, tissue triglycerides, and inflammation were evaluated and analyzed.