Rho-Kinase Is Differentially Expressed in the Adipose Tissue of Rodent and Human in Response to Aging, Sex, and Acute Exercise.

White adipose tissue (WAT) controls energy storage, expenditure, and endocrine function. Rho-kinase (ROCK) is related to impaired thermogenesis, downregulation of preadipocyte differentiation, and adipokine production. Furthermore, WAT ROCK responds to metabolic stress from high-fat diets or diabetes. However, ROCK distribution in adipose depots and its response to aging and sex remain unclear. Thus, we aim to investigate ROCK function in adipose tissue of rodent and human in response to aging and sex. We observed specific differences in the ROCK1/2 distribution in inguinal WAT (ingWAT), perigonadal WAT (pgWAT), and brown adipose tissue of male and female rodents. However, ROCK2 expression was lower in female ingWAT compared with males, a fact that was not observed in the other depots. In the pgWAT and ingWAT of male and female rodents, ROCK activity increased during development. Moreover, middle-aged female rodents and humans showed downregulation in ROCK activity after acute physical exercise. Interestingly, ROCK levels were associated with several inflammatory markers both in rats and humans WAT (Nfkb1, Tnf, Il1b, Il6, and Mcp1). Induction of cell senescence by etoposide elevates ROCK activity in human preadipocytes; however, silencing ROCK1/2 demonstrates improvement in the inflammatory and cell senescence state. Using public databases, several pathways were strongly associated with ROCK modulation in WAT. In summary, WAT ROCK increases with development in association with inflammatory markers. Further, ROCK activity was attenuated by acute physical exercise, implicating it as a possible therapeutic target for metabolism improvement mediated by adipose tissue inflammatory state changes.

Effects of short-term endurance and strength exercise in the molecular regulation of skeletal muscle in hyperinsulinemic and hyperglycemic Slc2a4+/- mice.

OBJECTIVE: Intriguingly, hyperinsulinemia, and hyperglycemia can predispose insulin resistance, obesity, and type 2 diabetes, leading to metabolic disturbances. Conversely, physical exercise stimulates skeletal muscle glucose uptake, improving whole-body glucose homeostasis. Therefore, we investigated the impact of short-term physical activity in a mouse model (Slc2a4+/-) that spontaneously develops hyperinsulinemia and hyperglycemia even when fed on a chow diet. METHODS: Slc2a4+/- mice were used, that performed 5 days of endurance or strength exercise training. Further analysis included physiological tests (GTT and ITT), skeletal muscle glucose uptake, skeletal muscle RNA-sequencing, mitochondrial function, and experiments with C2C12 cell line. RESULTS: When Slc2a4+/- mice were submitted to the endurance or strength training protocol, improvements were observed in the skeletal muscle glucose uptake and glucose metabolism, associated with broad transcriptomic modulation, that was, in part, related to mitochondrial adaptations. The endurance training, but not the strength protocol, was effective in improving skeletal muscle mitochondrial activity and unfolded protein response markers (UPRmt). Moreover, experiments with C2C12 cells indicated that insulin or glucose levels could contribute to these mitochondrial adaptations in skeletal muscle. CONCLUSIONS: Both short-term exercise protocols were efficient in whole-body glucose homeostasis and insulin resistance. While endurance exercise plays an important role in transcriptome and mitochondrial activity, strength exercise mostly affects post-translational mechanisms and protein synthesis in skeletal muscle. Thus, the performance of both types of physical exercise proved to be a very effective way to mitigate the impacts of hyperglycemia and hyperinsulinemia in the Slc2a4+/- mouse model.

Short-term flaxseed oil, rich in omega 3, protects mice against metabolic damage caused by high-fat diet, but not inflammation.

It is known that long-term high-fat diet (HF) feeding drastically affects the adipose tissue, contributing to metabolic disorders. Recently, short-term HF consumption was shown to affect different neuronal signaling pathways. Thus, we aimed to evaluate the inflammatory effects of a short-term HF and whether a diet containing omega-3 fatty acid fats from flaxseed oil (FS) has protective effects. Mice were divided into three groups for 3 d, according to their diets: Control group (CT), HF, or FS for 3 d. Lipid profiles were assessed through mass spectrometry and inflammatory markers by RT-qPCR and Western blotting. After short-term HF, mice increased food intake, body weight, adiposity, and fasting glucose. Increased mRNA content of Ccl2 and Tnf was demonstrated in the HF compared to CT in mesenteric adipose tissue. In the liver, TNFα protein was higher in the HF group than in CT, followed by a decreased polyunsaturated fatty acids tissue incorporation in HF. On the other hand, the consumption of FS reduced food intake and fasting glucose, as well as increased omega-3 fatty acid incorporation in MAT and the liver. However, short-term FS was insufficient to control the early inflammation triggered by HF in MAT and the liver. These data demonstrated that a 3-d HF diet is enough to damage glucose homeostasis and trigger inflammation. In contrast, short-term FS protects against increased food intake and fasting glucose but not inflammation in mice.

Resistance exercise attenuates IKKε phosphorylation and hepatic fat accumulation of obese mice.

Obesity is associated with low-grade inflammation and disturbances in hepatic metabolism. This study aimed to investigate the effects of resistance exercise on inflammatory signalling related to IκB kinase (IKK) ɛ protein (IKKɛ) and on hepatic fat accumulation in obese mice. Male Swiss mice were distributed into three groups: control (CTL) fed with standard chow; obese (OB) mice induced by a high-fat diet (HFD); obese exercised (OB + RE) mice fed with HFD and submitted to a resistance exercise training. The resistance exercise training protocol consisted of 20 sets/3 ladder climbs for 8 weeks, three times/week on alternate days. The training overload was equivalent to 70% of the maximum load supported by the rodent. Assays were performed to evaluate weight gain, hepatic fat content, fasting glucose, insulin sensitivity, IKKɛ phosphorylation and proteins related to insulin signalling and lipogenesis in the liver. Mice that received the high-fat diet showed greater adiposity, impaired insulin sensitivity, increased fasting glucose and increased hepatic fat accumulation. These results were accompanied by an increase in IKKɛ phosphorylation and lipogenesis-related proteins such as cluster of differentiation 36 (CD36) and fatty acid synthase (FAS) in the liver of obese mice. In contrast, exercised mice showed lower body weight and adiposity evolution throughout the experiment. In addition, resistance exercise suppressed the effects of the high-fat diet by reducing IKKɛ phosphorylation and hepatic fat content. In conclusion, resistance exercise training improves hepatic fat metabolism and glycaemic homeostasis, which are, at least in part, linked to the anti-inflammatory effect of reduced IKKɛ phosphorylation in the liver of obese mice.

12,13-diHOME as a new therapeutic target for metabolic diseases.

Lipokines are bioactive compounds, derived from adipose tissue depots, that control several molecular signaling pathways. Recently, 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME), an oxylipin, has gained prominence in the scientific literature. An increase in circulating 12,13-diHOME has been associated with improved metabolic health, and the action of this molecule appears to be mediated by brown adipose tissue (BAT). Scientific evidence indicates that the increase in serum levels of 12,13-diHOME caused by stimuli such as physical exercise and exposure to cold may favor the absorption of fatty acids by brown adipose tissue and stimulate the browning process in white adipose tissue (WAT). Thus, strategies capable of increasing 12,13-diHOME levels may be promising for the prevention and treatment of obesity and metabolic diseases. This review explores the relationship of 12,13-diHOME with brown adipose tissue and its role in the metabolic health context, as well as the signaling pathways involved between 12,13-diHOME and BAT.

Time-restricted feeding combined with aerobic exercise training can prevent weight gain and improve metabolic disorders in mice fed a high-fat diet.

KEY POINTS: Time-restricted feeding (TRF, in which energy intake is restricted to 8 h/day during the dark phase) alone or combined with aerobic exercise (AE) training can prevent weight gain and metabolic disorders in Swiss mice fed a high-fat diet. The benefits of TRF combined with AE are associated with improved hepatic metabolism and decreased hepatic lipid accumulation. TRF combined with AE training increased fatty acid oxidation and decreased expression of lipogenic and gluconeogenic genes in the liver of young male Swiss mice. TRF combined with AE training attenuated the detrimental effects of high-fat diet feeding on the insulin signalling pathway in the liver. ABSTRACT: Time-restricted feeding (TRF) or physical exercise have been shown to be efficient in the prevention and treatment of metabolic disorders; however, the additive effects of TRF combined with aerobic exercise (AE) training on liver metabolism have not been widely explored. In this study TRF (8 h in the active phase) and TRF combined with AE (TRF+Exe) were compared in male Swiss mice fed a high-fat diet, with evaluation of the effects on insulin sensitivity and expression of hepatic genes involved in fatty acid oxidation, lipogenesis and gluconeogenesis. As in previous reports, we show that TRF alone (eating only between zeitgeber time 16 and 0) was sufficient to reduce weight and adiposity gain, increase fatty acid oxidation and decrease lipogenesis genes in the liver. In addition, we show that mice of the TRF+Exe group showed additional adaptations such as increased oxygen consumption ( V̇O2${\dot V_{{{\rm{O}}_{\rm{2}}}}}$ ), carbon dioxide production ( V̇CO2${\dot V_{{\rm{C}}{{\rm{O}}_{\rm{2}}}}}$ ) and production of ketone bodies (ß-hydroxybutyrate). Also, TRF+Exe attenuated the negative effects of high-fat diet feeding on the insulin signalling pathway (insulin receptor, insulin receptor substrate, Akt), and led to increased fatty acid oxidation (Ppara, Cpt1a) and decreased gluconeogenic (Fbp1, Pck1, Pgc1a) and lipogenic (Srebp1c, Cd36) gene expression in the liver. These molecular results were accompanied by increased glucose metabolism, lower serum triglycerides and reduced hepatic lipid content in the TRF+Exe group. The data presented in this study show that TRF alone has benefits but TRF+Exe has additive benefits and can mitigate the harmful effects of consuming a high-fat diet on body adiposity, liver metabolism and glycaemic homeostasis in young male Swiss mice.

Omega-3 mechanism of action in inflammation and endoplasmic reticulum stress in mononuclear cells from overweight non-alcoholic fatty liver disease participants: study protocol for the "Brazilian Omega Study" (BROS)-a randomized controlled trial.

The low-grade inflammation is pivotal in obesity and its comorbidities; however, the inflammatory proteins are out of target for traditional drug therapy. Omega-3 (ω3) fatty acids can modulate the downstream signaling of Toll-like receptor (TLR) and tumor necrosis factor-α receptor (TNFα) through GPR120, a G-protein-coupled receptor, a mechanism not yet elucidated in humans. This work aims to investigate if the ω3 supplementation, at a feasible level below the previously recommended level in the literature, is enough to disrupt the inflammation and endoplasmic reticulum stress (ER-stress), and also if in acute treatment (3 h) ω3 can activate the GPR120 in peripheral blood mononuclear cells (PBMC) and leukocytes from overweight non-alcoholic fatty liver disease (NAFLD) participants. The R270H variant of the Ffar4 (GPR120 gene) will also be explored about molecular responses and blood lipid profiles. A triple-blind, prospective clinical trial will be conducted in overweight men and women, aged 19-75 years, randomized into placebo or supplemented (2.2 g of ω3 [EPA+DHA]) groups for 28 days. For sample calculation, it was considered the variation of TNFα protein and a 40% dropout rate, obtaining 22 individuals in each group. Volunteers will be recruited among patients with NAFLD diagnosis. Anthropometric parameters, food intake, physical activity, total serum lipids, complete fatty acid blood profile, and glycemia will be evaluated pre- and post-supplementation. In the PBMC and neutrophils, the protein content and gene expression of markers related to inflammation (TNFα, MCP1, IL1ß, IL6, IL10, JNK, and TAK1), ER-stress (ATF1, ATF6, IRE1, XBP1, CHOP, eIF2α, eIF4, HSP), and ω3 pathway (GPR120, ß-arrestin2, Tab1/2, and TAK1) will be evaluated using Western blot and RT-qPCR. Participants will be genotyped for the R270H (rs116454156) variant using the TaqMan assay. It is hypothesized that attenuation of inflammation and ER-stress signaling pathways in overweight and NAFLD participants will be achieved through ω3 supplementation through binding to the GPR120 receptor. TRIAL REGISTRATION: ClinicalTrials.gov #RBR-7x8tbx. Registered on May 10, 2018, with the Brazilian Registry of Clinical Trials.

Mitochondrial dysfunction plays an essential role in remodeling aging adipose tissue.

Aging is characterized by several physiological changes in the human body, such as the remodeling/redistribution of body fat, highlighted by the increase in fat in the abdominal region due to reduced fat in the peripheral limbs. Abdominal fat is related to metabolic complications and an increased risk for developing diseases such as obesity, type 2 diabetes mellitus, and hypertension. Understanding this process is crucial for developing new therapeutic strategies able to mitigate its impact. This redistribution of fat has been associated with lower activation of brown adipose tissue over the years of life. Brown adipose tissue differs from white adipose tissue, mainly because it produces heat, increasing energy expenditure. Current evidence points to morphological and functional changes in mitochondria during aging, a key mechanism for understanding the dysmetabolic and pro-inflammatory phenotype associated with senescence. Therefore, this minireview will focus on how aging-induced mitochondrial changes are involved in the remodeling/redistribution of body fat.

Taurine supplementation in conjunction with exercise modulated cytokines and improved subcutaneous white adipose tissue plasticity in obese women.

Interventions that can modulate subcutaneous white adipose tissue (scWAT) function, such as exercise training and nutritional components, like taurine, modulate the inflammatory process, therefore, may represent strategies for obesity treatment. We investigated the effects of taurine supplementation in conjunction with exercise on inflammatory and oxidative stress markers in plasma and scWAT of obese women. Sixteen obese women were randomized into two groups: Taurine supplementation group (Tau, n = 8) and Taurine supplementation + exercise group (Tau + Exe, n = 8). The intervention was composed of daily taurine supplementation (3 g) and exercise training for 8 weeks. Anthropometry, body fat composition, and markers of inflammatory and oxidative stress were determined in plasma and scWAT biopsy samples before and after the intervention. We found that, although taurine supplementation increased taurine plasma levels, no changes were observed for the anthropometric characteristics. However, Tau alone decreased interleukin-6 (IL-6), and in conjunction with exercise (Tau + Exe), increased anti-inflammatory interleukins (IL-15 and IL10), followed by reduced IL1ß gene expression in the scWAT of obese women. Tau and Tau + Exe groups presented reduced adipocyte size and increased connective tissue and multilocular droplets. In conclusion, taurine supplementation in conjunction with exercise modulated levels of inflammatory markers in plasma and scWAT, and improved scWAT plasticity in obese women, promoting protection against obesity-induced inflammation. TRN NCT04279600 retrospectively registered on August 18, 2019.

Taurine supplementation associated with exercise increases mitochondrial activity and fatty acid oxidation gene expression in the subcutaneous white adipose tissue of obese women.

PURPOSE: To evaluate the effects of taurine supplementation associated or not with chronic exercise on body composition, mitochondrial function, and expression of genes related to mitochondrial activity and lipid oxidation in the subcutaneous white adipose tissue (scWAT) of obese women. METHODS: A randomized and double-blind trial was developed with 24 obese women (BMI 33.1 ± 2.9 kg/m2, 32.9 ± 6.3 y) randomized into three groups: Taurine supplementation group (Tau, n = 8); Exercise group (Ex, n = 8); Taurine supplementation + exercise group (TauEx, n = 8). The intervention was composed of 3 g of taurine or placebo supplementation and exercise training for eight weeks. Anthropometry, body fat composition, indirect calorimetry, scWAT biopsy for mitochondrial respiration, and gene expression related to mitochondrial activity and lipid oxidation were assessed before and after the intervention. RESULTS: No changes were observed for the anthropometric characteristics. The Ex group presented an increased resting energy expenditure rate, and the TauEx and Ex groups presented increased lipid oxidation and a decreased respiratory quotient. Both trained groups (TauEx and Ex) demonstrated improved scWAT mitochondrial respiratory capacity. Regarding mitochondrial markers, no changes were observed for the Tau group. The TauEx group had higher expression of CIDEA, PGC1a, PRDM16, UCP1, and UCP2. The genes related to fat oxidation (ACO2 and ACOX1) were increased in the Tau and Ex groups, while only the TauEx group presented increased expression of CPT1, PPARa, PPARγ, LPL, ACO1, ACO2, HSL, ACOX1, and CD36 genes. CONCLUSION: Taurine supplementation associated with exercise improved lipid metabolism through the modulation of genes related to mitochondrial activity and fatty acid oxidation, suggesting a browning effect in the scWAT of obese women.

Aging is associated with increased TRB3, ER stress, and hepatic glucose production in the liver of rats.

TRB3, a mammalian homolog of Drosophila tribbles, plays an important role in multiple tissues and it has been implicated in stress response regulation and metabolic control. However, the role of hepatic TRB3 and its relationship with endoplasmic reticulum stress (ER stress) during aging has not been elucidated. Thus, the present study aimed to explore the association of aging with TRB3 and ER stress on the hepatic glucose production in Wistar rats. We found the TRB3 protein content to be higher in livers of old rats (27 months) compared to young (3 months) and middle-aged (17 months) rats. The increased content of hepatic TRB3 of the old rats was associated with insulin resistance (decreased protein kinase B (Akt) and Forkhead Box O1 (FoxO1) phosphorylation) and increased enzymes of gluconeogenesis (phosphoenolpyruvate carboxykinase (PEPCK) and Glucose 6-phosphatase (G6Pase)). Moreover, aging was associated with activation of the endoplasmic reticulum stress pathway-related molecules, with an increase in phosphorylation of Inositol-requiring enzyme 1 (p-IRE1α), the protein kinase RNA-like endoplasmic reticulum kinase (p-PERK), eukaryotic translation initiation factor-α (p-eIF2α), binding immunoglobulin protein (BiP), and the C/EBP homologous protein (CHOP) contents in rats. These molecular changes resulted in increased liver glucose production in response to the pyruvate challenge and hyperglycemia of the old rats. In conclusion, our results suggested that, by interfering with insulin signaling in the liver, TRB3 was associated with ER stress and increased hepatic glucose production in aging rats.

Physical exercise increases ROCK activity in the skeletal muscle of middle-aged rats.

The physical exercise is a potential strategy to control age-related metabolic disorders, such as insulin resistance, impaired glucose homeostasis, and type 2 diabetes. Rho-kinase (ROCK) increases skeletal muscle glucose uptake through Insulin Receptor Substrate 1 (IRS1) phosphorylation. Here, we investigated the role of physical exercise in ROCK pathway in the skeletal muscle of Fischer middle-aged rats. Firstly, we observed the ROCK distribution in different skeletal muscle fiber types. ROCK signaling pathway (ROCK1 and ROCK2) and activity (pMYPT1) were higher in the soleus, which was associated with increased insulin signaling pathway (pIR, pIRS1, pPDK, pGSK3ß). Middle-aged rats submitted to physical exercise, showed the upregulation of ROCK2 content and normalized RhoA (ROCK activator enzyme) levels in soleus muscle compared with middle-aged sedentary rats. These molecular changes in middle-aged exercised rats were accompanied by higher insulin signaling (pIRS1, pGSK3ß, pAS160, GLUT4) in the soleus muscle. Reinforcing these findings, when pharmacological inhibition of ROCK activity was performed (using Y-27632), the insulin signaling pathway and glucose metabolism-related genes (Tpi, Pgk1, Pgam2, Eno3) were decreased in the soleus muscle of exercised rats. In summary, ROCK signaling seems to contribute with whole-body glucose homeostasis (∼50 %) through its higher upregulation in the soleus muscle in middle-aged exercised rats.

The Effects of Aging on Rho-Kinase and Insulin Signaling in Skeletal Muscle and White Adipose Tissue of Rats.

The insulin receptor substrate 1 regulates insulin-mediated glucose uptake and is a target of Rho-kinase (Rock); however, the relationship between age-related insulin resistance and Rock signaling specifically in skeletal muscle and adipose tissue is unknown. We evaluated the content and activity of Rock in C2C12 myotubes, and in skeletal muscle and white adipose tissue (WAT) from two rodent models that differ in their patterns of body fat accumulation during aging (Wistar and Fischer 344 rats). Body fat gain in the Wistar rats was greater than in Fischer rats and only Wistar rats had impairment of whole-body insulin sensitivity. Rock activity and insulin signaling were impaired in skeletal muscle in both rat models, but only middle-aged Wistar rats had higher Rock activity in WAT. These data are consistent with a positive role of Rock in regulating insulin signaling in both skeletal muscle and its negative role in the adipose tissue, suggesting that Rock activity in adipose tissue is important in age-related insulin resistance.

Short-term Resistance Training Increases APPL1 Content in the Liver and the Insulin Sensitivity of Mice Fed a Long-term High-fat Diet.

BACKGROUND: APPL1, an adapter protein, interact directly with adiponectin receptors mediating adiponectin signaling and acting as a critical regulator of the crosstalk between adiponectin and insulin signaling pathway. The inadequate level of physical activity, high-calorie intake, or both lead to adverse consequences on health, like insulin resistance. On the order hand, physical exercise acts positively in the insulin action. PURPOSE: Here, we investigated the effects of short-term resistance training (RT) on APPL1 content and adiponectin pathway in the liver of mice fed a long-term high-fat diet. METHODS: Swiss mice were distributed into 3 groups: Mice that fed a chow diet (CTR); Mice fed a high-fat diet for 16 months (HFD); and mice fed a high-fat diet for 16 months and submitted to a climbing ladder exercise (RT) for 7 days (HFD-EXE). RESULTS: The results show that short-term RT increases the APPL1 content but wasn't able to alter AdipoR1 and AdipoR2 content in the liver of HFD-EXE mice. However, this increase in the APPL1 content in response to RT was accompanied by improvement in the insulin sensitivity. CONCLUSION: In summary, our data suggested that short-term RT improves glycemic homeostasis and increases APPL1 in the hepatic tissue of mice treated with long-term high-fat diet.

Occurrence of overweight in schoolchildren and analysis of agreement between anthropometric methods / Ocorrência de excesso de peso em escolares e análise da concordância entre métodos antropométricos

Abstract The child population is strongly affected by obesity. Accessible and reliable strategies for the obesity diagnosis are of utmost importance.. The aim of this study was to identify childhood obesity according the WHO (World Health Organization): malnourished, healthy weight, overweight and obese. It was collected measures of height, Body Mass Index (BMI), Waist Circumference (WC) and Triceps Skinfold Thickness (TSF) of 449 children from Municipal School of Araras/SP, from 7 to 10 years old. It was performed a Spearman correlation test between BMI, WC and TSF variables. Also, was realized cross tabulation between the found results by the different methods, constructing a contingency table 2x2, with absolute frequency of boys and girls classified as "without overweight" and "with overweight". The concordance between methods was analyzed by kappa index. In the results, 28.3% of children presented overweight according to BMI, with higher prevalence in boys. Generally, the found results through TSF showed strong correlation with both BMI and WC (rs=0.7994 e rs=0.7519, respectively). The same was observed when data was analyzed separately by sex. When crossed the TSF data with BMI and WC, the kappa index demonstrated a satisfactory concordance (0.4419 e 0.5161, respectively). The TSF can be suggested a method to body composition assessment and cardiometabolic risk in children.

Resumo A população infantil mostra-se fortemente atingida pela obesidade. Estratégias acessíveis e confiáveis para o diagnóstico da obesidade são de extrema importância. O objetivo desse estudo foi identificar a obesidade infantil de acordo com a OMS (Organização Mundial de Saúde): desnutridas, peso saudável, sobrepeso e obesas. Foram coletadas medidas de estatura, Índice de Massa Corporal (IMC), Circunferência abdominal (CA) e Dobra Cutânea Tricipital (DCT) de 449 crianças de uma Escola Municipal na cidade de Araras/SP, de 7 a 10 anos de idade. Foi realizado o teste de correlação de Spearman entre as variáveis IMC, CA e DCT. Também foi realizado tabulação cruzada entre os resultados encontrados pelos diferentes métodos, construindo uma tabela de contingência 2x2, com a frequência absoluta de meninos e meninas classificados como "sem excesso de peso" e "com excesso de peso". A concordância entre os métodos foi analisada pelo índice kappa. Nos resultados 28,3% das crianças apresentaram excesso de peso de acordo com o IMC, com maior ocorrência entre os meninos. De modo geral, os resultados encontrados por meio da DCT apresentaram forte correlação tanto com IMC quanto com CA (rs=0,7994 e rs=0,7519, respectivamente). O mesmo foi observado quando analisados separadamente por sexo. Quando cruzados os dados de DCT com os de IMC e CA, o índice kappa revelou uma satisfatória concordância (0,4419 e 0,5161, respectivamente). A DCT pode ser sugerido como um método para investigação de composição corporal e risco cardiometabólico de crianças.

Mapping Research in the Obesity, Adipose Tissue, and MicroRNA Field: A Bibliometric Analysis.

Recent studies have investigated the control of adipose tissue expansion and inflammatory process by microRNAs (miRNAs). These two processes are of great interest because both are associated with obesity and metabolic syndrome. However, despite the great relevance of the role of miRNAs in obesity and adipose tissue, no qualitative and quantitative analysis on the subject has been performed. Thus, we aimed to examine global research activity and current trends with respect to the interaction between obesity, adipose tissue and miRNAs through a bibliometric analysis. This research was performed on the Scopus database for publications containing miRNA, obesity, and adipose tissue keyword combinations. In total, 898 articles were analyzed and the most frequently occurring keywords were selected and clustered into three well-defined groups. As a result, first group of keywords pointed to the research area on miRNAs expressed in obesity-associated diseases. The second group demonstrated the regulation of the adipogenesis process by miRNAs, while the third group highlighted brown adipose tissue and thermogenesis as one of the latest global research trends related to the theme. The studies selected in this paper describe the expression and performance of different miRNAs in obesity and comorbidities. Most studies have focused on identifying miRNAs and signaling pathways associated with obesity, type 2 diabetes mellitus, and cardiovascular disease. Thus, the miRNA profile for these diseases may be used as biomarkers and therapeutic targets in the prevention and treatment of obesity-associated diseases.

Rho-kinase activity is upregulated in the skeletal muscle of aged exercised rats.

There is a gap in the knowledge regarding the regulation of glucose uptake in skeletal muscle during the development of insulin resistance in the elderly. Rho-Kinase (Rock) signaling has been demonstrated as a crucial mechanism related to glucose metabolism and insulin sensitivity in skeletal muscle. This kinase is involved in the insulin receptor substrate 1 (IRS1) phosphorylation, leading to glucose uptake stimulation in the skeletal muscle; however, the mechanisms elucidating the role of Rock regulation in the context of advanced ages are still limited. In this study, we submitted old Fischer 344 rats to short-term treadmill physical exercise protocol (5 days) and evaluated the glucose tolerance and proteins involved with Rock/insulin signaling in the skeletal muscle. Compared to young rats, the old rats showed glucose intolerance, hyperinsulinemia, and decreased phosphorylation in the proteins related to the insulin signaling pathway in the skeletal muscle, without changes in body mass and adiposity. Otherwise, when these rats were submitted to physical exercise, it was found decreased fasting glucose, higher glucose tolerance, decreased insulinemia, and upregulation of Rock2/pIRS1/pAkt/pGSK3ß/GLUT4 pathway in the skeletal muscle. In summary, the aging process did not change Rock signaling, but the physical exercise was able to increase Rock2 content and insulin signaling pathway in the skeletal muscle. This finding suggests the benefic role of physical exercise to advanced ages, promoting insulin-sensitive effects with Rho-kinase contribution.

Acute physical exercise increases APPL1/PI3K signaling in the hypothalamus of lean mice.

Adiponectin is an adipokine that acts in the control of energy homeostasis. The adaptor protein containing the pleckstrin homology domain, phosphotyrosine-binding domain, and leucine zipper motif 1 (APPL1) is a key protein in the adiponectin signaling. The APPL1 mediates a positive effect on the insulin signaling through the interaction with the phosphoinositide 3-kinase (PI3K). Thus, the present study aimed to explore the effects of an acute physical exercise session on the hypothalamic adiponectin signaling. Firstly, using bioinformatics analysis, we found a negative correlation between hypothalamic APPL1 mRNA levels and food consumption in several strains of genetically diverse BXD mice. Also, the mice and the human database revealed a positive correlation between the levels of APPL1 mRNA and PI3K mRNA. At the molecular level, the exercised mice showed increased APPL1 and PI3K (p110) protein contents in the hypothalamus of Swiss mice. Furthermore, the exercise increases co-localization between APPL1 and PI3K p110 predominantly in neurons of the arcuate nucleus of hypothalamus (ARC). Finally, we found an acute exercise session reduced the food intake 5 hr after the end of fasting. In conclusion, our results indicate that physical exercise reduces the food intake and increases some proteins related to adiponectin pathway in the hypothalamus of lean mice.

Short-term high-fat diet modulates several inflammatory, ER stress, and apoptosis markers in the hippocampus of young mice.

The consumption of saturated fatty acids is one of the leading risk factors for Alzheimer's Disease (AD) development. Indeed, the short-term consumption of a high-fat diet (HFD) is related to increased inflammatory signals in the hippocampus; however, the potential molecular mechanisms linking it to AD pathogenesis are not fully elucidated. In our study, we investigated the effects of short-term HFD feeding (within 3, 7 and 10 days) in AD markers and neuroinflammation in the hippocampus of mice. The short period of HFD increased fasting glucose and HOMA-IR. Also, mice fed HFD increased the protein content of ß-Amyloid, pTau, TNFα, IL1ß, pJNK, PTP1B, peIF2α, CHOP, Caspase3, Cleaved-Caspase3 and Alzheimer-related genes (Bax, PS1, PEN2, Aph1b). At 10 days, both neuronal (N2a) and microglial (BV2) cells presented higher expression of inflammatory and apoptotic genes when stimulated with palmitate. These findings suggest that a short period of consumption of a diet rich in saturated fat is associated with activation of inflammatory, ER stress and apoptotic signals in the hippocampus of young mice.