Sleep deprivation induces pathological changes in rat masticatory muscles: Role of Toll like signaling pathway and atrophy.

The aim of this study was to evaluate the Toll like signaling pathway and atrophy after sleep deprivation (SD) in rat masticatory muscles: masseter and temporal. A total of 24 animals was distributed into three groups: Control group (CTL, n = 8), subjected to SD for 96 h (SD96, n = 8) and subjected to SD for 96 h more 96 h of sleep recovery (SD96 + R, n = 8). Histopathological analysis revealed the presence of acute inflammatory cells, congested vessels, fibrosis, and high cellularity in the skeletal muscle fibers from masseter and temporal submitted to SD. These morphological alterations were not observed in the control group since neither inflammatory cells nor congested vessels were observed to this group. In the group SD96 + R, the absence of inflammation was noticed to the masseter only. In this group, COX-2 and TNF-alpha downregulation were detected when comparing to control group. MyD88 and pIKK decreased in SD96 and SD96 + R groups being pNFKBp50 downregulatated in SD96 + R. MyD88 expression increased in rats submitted to SD96 and SD96 + R in temporal when compared to control group. On the other hand, pIKK decreased the protein expression in groups SD96 and SD96 + R while pNFKBp50 showed a decreased protein expression in group SD96 only. The activation of atrophy by means of MAFbx upregulation was detected in temporal muscle in SD96 and SD96 + R when compared to control. In summary, our results show that SD is able to induce morphological alterations in rat masticatory muscles. Toll like signaling pathway and atrophy play important roles in ethiopathogenesis induced by SD, being dependent of skeletal muscle type.

Macadamia oil supplementation attenuates inflammation and adipocyte hypertrophy in obese mice.

Excess of saturated fatty acids in the diet has been associated with obesity, leading to systemic disruption of insulin signaling, glucose intolerance, and inflammation. Macadamia oil administration has been shown to improve lipid profile in humans. We evaluated the effect of macadamia oil supplementation on insulin sensitivity, inflammation, lipid profile, and adipocyte size in high-fat diet (HF) induced obesity in mice. C57BL/6 male mice (8 weeks) were divided into four groups: (a) control diet (CD), (b) HF, (c) CD supplemented with macadamia oil by gavage at 2 g/Kg of body weight, three times per week, for 12 weeks (CD + MO), and (d) HF diet supplemented with macadamia oil (HF + MO). CD and HF mice were supplemented with water. HF mice showed hypercholesterolemia and decreased insulin sensitivity as also previously shown. HF induced inflammation in adipose tissue and peritoneal macrophages, as well as adipocyte hypertrophy. Macadamia oil supplementation attenuated hypertrophy of adipocytes and inflammation in the adipose tissue and macrophages.

Anthocyanins ameliorate obesity-associated metainflammation: Preclinical and clinical evidence.

The growing rates of obesity worldwide call for intervention strategies to help control the pathophysiological consequences of weight gain. The use of natural foods and bioactive compounds has been suggested as such a strategy because of their recognized antioxidant and anti-inflammatory properties. For example, polyphenols, especially anthocyanins, are candidates for managing obesity and its related metabolic disorders. Obesity is well known for the presence of metainflammation, which has been labeled as an inflammatory activation that leads to a variety of metabolic disorders, usually related to increased oxidative stress. Considering this, anthocyanins may be promising natural compounds able to modulate several intracellular mechanisms, mitigating oxidative stress and metainflammation. A wide variety of foods and extracts rich in anthocyanins have become the focus of research in the field of obesity. Here, we bring together the current knowledge regarding the use of anthocyanins as an intervention tested in vitro, in vivo, and in clinical trials to modulate metainflammation. Most recent research applies a wide variety of extracts and natural sources of anthocyanins, in diverse experimental models, which represents a limitation of the research field. However, the literature is sufficiently consistent to establish that the in-depth molecular analysis of gut microbiota, insulin signaling, TLR4-triggered inflammation, and oxidative stress pathways reveals their modulation by anthocyanins. These targets are interconnected at the cellular level and interact with one another, leading to obesity-associated metainflammation. Thus, the positive findings with anthocyanins observed in preclinical models might directly relate to the positive outcomes in clinical studies. In summary and based on the entirety of the relevant literature, anthocyanins can mitigate obesity-related perturbations in gut microbiota, insulin resistance, oxidative stress and inflammation and therefore may contribute as a therapeutic tool in people living with obesity.

A low-carbohydrate diet with different fatty acids' sources in the treatment of obesity: Impact on insulin resistance and adipogenesis.

BACKGROUND: The search for nutritional intervention strategies against obesity has grown, highlighting the low-carbohydrate diet model. However, little is known about the impact of the quality of fatty acids consumed in this diet. Thus, we aim to investigate the influence of fatty acid quality on dietary strategy on obesity. METHODS: Male Swiss mice were diet-induced to obesity. Afterward, mice consume a low-carb diet with different types of fat: saturated, polyunsaturated ω-3, ω-6, and monounsaturated ω-9 fatty acids. Weight gain and food consumption were monitored weekly. An oral glucose tolerance test was performed and blood and tissue samples were collected for analysis of insulin resistance markers. Protein expression of insulin signaling pathway molecules, lipid metabolism, mitochondrial function, macrophage polarization, and cytokine production were analyzed. RESULTS: The high-fat diet was able to induce obesity and glucose intolerance. The switch to a low-carbohydrate dietary pattern reversed the glucose intolerance, with better results in the ω-3 and ω-9 groups. After the low-carbohydrate diet, groups ω-3 and ω-9 presented improved fasting serum glucose, insulin, and HOMA indexes. The low-carbohydrate diet also increased the activity of insulin pathway proteins such as IR, IRS1, and AKT. Furthermore, the ω-3 diet group showed greater activity of mitochondrial complexes and AMPK signaling pathway proteins. The ω-6 and ω-9 -rich diet induced M2-type macrophage polarization, as well as cytokine production modulation by the low-carbohydrate diet in the ω-3 and ω-9 groups. CONCLUSIONS: Consuming a low-carbohydrate diet pattern promotes weight loss and improves glucose intolerance in obesity. Also, the quality of lipids has a direct influence, demonstrating that the consumption of ω-3 polyunsaturated and ω-9 monounsaturated lipids can lead to more favorable outcomes for the improvement of glucose intolerance, lipid metabolism, and anti-inflammatory effects.

Supplementation of carotenoids from peach palm waste (Bactris gasipaes) obtained with an ionic liquid mediated process displays kidney anti-inflammatory and antioxidant outcomes.

Sustainable extraction processes based on alternative solvents to recover bioactive compounds of different raw materials have been highlighted as excellent alternatives to supply the needs of society towards a bioeconomy strategy. Little is known about the safety and biological effect of compounds extracted by these processes. In this work, carotenoids from Bactris gasipaes wastes obtained by an IL-based process were investigated in terms of safety, anti-inflammatory and, antioxidant activity in a high-fat-diet animal model on the kidney. Wistar rats were supplemented or not by carotenoids extracted with IL or VOS. The animals supplemented with carotenoids had lower weight than control and high-fat diets. In the animals supplemented with carotenoids, the group IL improved anti-inflammatory and antioxidant activity compared with carotenoids obtained by VOS. Also, the group HFD-VOS showed moderate-severe injuries on the kidney. Then, ILs could represent a novel tool for natural pigments safely applied to food industry.

Anti-inflammatory effects of oleic acid and the anthocyanin keracyanin alone and in combination: effects on monocyte and macrophage responses and the NF-κB pathway.

Monocyte recruitment and activation of macrophages are essential for homeostasis but are also related to the development and progression of cardiometabolic diseases. The management of inflammation with dietary components has been widely investigated. Two components that may influence inflammation are unsaturated fatty acids such as oleic acid (OA; 18:1cis-9) and antioxidant compounds like anthocyanins. Molecular and metabolic effects of such bioactive compounds are usually investigated in isolation, whereas they may be present in combination in foods or the diet. Considering this, we aimed to analyze the effects of OA and the anthocyanin keracyanin (AC) alone and in combination on toll-like receptor-mediated inflammatory responses in monocytes and macrophages. For this, THP-1-derived macrophages and monocytes were exposed to 3 treatments: OA, AC, or the combination (OAAC) and then stimulated with lipopolysaccharide. Inflammation-related gene expression and protein concentrations of IL-1ß, TNF-α, IL-6, MCP-1, and IL-10 were assessed. Also, NFκBp65, IκBα, and PPAR-γ protein expression were determined. OA, AC, and OAAC decreased pNFκBp65, PPARγ, IκBα, TNF-α, IL-1ß, IL-6, and MCP-1 and increased IL-10. MCP-1 protein expression was lower with OAAC than with either OA and AC alone. Compared to control, OAAC decreased mRNA for TLR4, IκKα, IκBα, NFκB1, MCP-1, TNF-α, IL-6, and IL-1ß more than OA or AC did alone. Also, IL-10 mRNA was increased by OAAC compared with control, OA, and AC. In summary, OA and AC have anti-inflammatory effects individually but their combination (OAAC) exerts a greater effect.

Carotenoids obtained from an ionic liquid-mediated process display anti-inflammatory response in the adipose tissue-liver axis.

Ionic liquids (ILs) have been proposed as more efficient and sustainable solvents to replace volatile organic solvents (VOSs). However, the drawbacks associated with their use are still limiting the regular application of bioactive compounds obtained from the processes they mediate as food ingredients. It is true that the number of ILs approved by the Food and Drug Administration for food applications is still low and mainly focused on the ones from the quaternary ammonium family. However, this trend is changing, judging from the evidence that industries are surpassing overgeneralization about ILs (on price and toxicity) and starting to consider the potential and performance of ILs as solvents. Despite the examples of industries applying ILs in their processes, the use of bioactive compounds obtained from IL-based processes as ingredients in food formulations is still a big challenge. The positive influence of carotenoids on diseases associated or originating from the inflammatory scenario including, among others, obesity, is not new. Moreover, it is also well known that the poorest population worldwide does not have the recommended intake of carotenoids, especially those pro-vitaminic A. In an attempt to help answer this issue, dietary supplements containing adequate doses of natural carotenoids are expected to be the solution, or at least, part of the solution for a healthier life, but also, to reduce hunger. Thus, complete studies evaluating the toxicological potential and the real viability of adding these bioactive compounds in food formulations proving (or not!) their safety to consumers and handlers are highly demanded. This work proposes to investigate the potential of carotenoids extracted from Bactris gasipaes feedstocks mediated by an ethanolic solution of an imidazolium-based IL. Thus, male Wistar rats were randomized in six different groups, supplemented or not by carotenoids extracted by IL or VOS, and fed by control- and/or high-fat-diets (HFD). The adipose tissue-liver axis was studied as a model to investigate the influence of the carotenoids on the levels of inflammation and oxidative stress markers. The main results showed that animals supplemented with carotenoids extracted with IL displayed improvements in serum parameters, besides lower metabolic efficiency, and antioxidant response on the liver, even when fed with HFD. However, animals supplemented with carotenoids extracted by VOS showed higher levels of pro-inflammatory markers and huge oxidative stress on the liver.

Decaffeinated green tea extract rich in epigallocatechin-3-gallate prevents fatty liver disease by increased activities of mitochondrial respiratory chain complexes in diet-induced obesity mice.

Nonalcoholic fatty liver disease has been considered the hepatic manifestation of obesity. It is unclear whether supplementation with green tea extract rich in epigallocatechin-3-gallate (EGCG) influences the activity of mitochondrial respiratory chain complexes and insulin resistance in the liver. EGCG regulated hepatic mitochondrial respiratory chain complexes and was capable of improving lipid metabolism, attenuating insulin resistance in obese mice. Mice were divided into four groups: control diet+water (CW) or EGCG (CE) and hyperlipidic diet+water (HFW) or EGCG (HFE). All animals received water and diets ad libitum for 16 weeks. Placebo groups received water (0.1 ml/day) and EGCG groups (0.1 ml EGCG and 50 mg/kg/day) by gavage. Cytokines concentrations were obtained by ELISA, protein expression through Western blotting and mitochondrial complex enzymatic activity by colorimetric assay of substrate degradation. HFW increased body weight gain, adiposity index, retroperitoneal and mesenteric adipose tissue relative weight, serum glucose, insulin and Homeostasis Model Assessment of Basal Insulin Resistance (HOMA-IR); glucose intolerance was observed in oral glucose tolerance test (OGTT) as well as ectopic fat liver deposition. HFE group decreased body weight gain, retroperitoneal and mesenteric adipose tissue relative weight, HOMA-IR, insulin levels and liver fat accumulation; increased complexes II-III and IV and malate dehydrogenase activities and improvement in glucose uptake in OGTT and insulin sensitivity by increased protein expression of total AKT, IRα and IRS1. We did not find alterations in inflammatory parameters analyzed. EGCG was able to prevent obesity stimulating the mitochondrial complex chain, increasing energy expenditure, particularly from the oxidation of lipid substrates, thereby contributing to the prevention of hepatic steatosis and improved insulin sensitivity.

Green Tea Extract Rich in Epigallocatechin-3-Gallate Prevents Fatty Liver by AMPK Activation via LKB1 in Mice Fed a High-Fat Diet.

Supplementation with epigallocatechin-3-gallate has been determined to aid in the prevention of obesity. Decaffeinated green tea extract appears to restore a normal hepatic metabolic profile and attenuate high-fat diet (HFD)-induced effects, thereby preventing non-alcoholic fatty liver disease in mice. Mice were maintained on either a control diet (CD) or HFD for 16 weeks and supplemented with either water or green tea extract (50 mg/kg/day). The body mass increase, serum adiponectin level, and lipid profile were measured over the course of the treatment. Furthermore, the AMPK pathway protein expression in the liver was measured. From the fourth week, the weight gain in the CD + green tea extract (CE) group was lower than that in the CD + water (CW) group. From the eighth week, the weight gain in the HFD + water (HFW) group was found to be higher than that in the CW group. Moreover, the weight gain in the HFD + green tea extract (HFE) group was found to be lower than that in the HFW group. Carcass lipid content was found to be higher in the HFW group than that in the CW and HFE groups. Serum analysis showed reduced non-esterified fatty acid level in the CE and HFE groups as compared with their corresponding placebo groups. Increased adiponectin level was observed in the same groups. Increased VLDL-TG secretion was observed in the HFW group as compared with the CW and HFE groups. Increased protein expression of AdipoR2, SIRT1, pLKB1, and pAMPK was observed in the HFE group, which explained the reduced expression of ACC, FAS, SREBP-1, and ChREBP in this group. These results indicate that the effects of decaffeinated green tea extract may be related to the activation of AMPK via LKB1 in the liver of HFD-fed mice.

Green tea extract improves high fat diet-induced hypothalamic inflammation, without affecting the serotoninergic system.

To investigate possible mechanisms of green tea's anti-obesity and anti-diabetic effects in the hypothalamus, the central regulator of metabolism, of mice fed with high-fat diet (HFD), we analyzed proteins of the toll-like receptor 4 (TLR4) pathway and serotoninergic proteins involved in energy homeostasis. Thirty-day-old male Swiss mice were fed with HFD rich in saturated fat and green tea extract (GTE) for 8 weeks. After that, body weight and mass of fat depots were evaluated. Oral glucose tolerance test was performed 3 days prior to euthanasia; serum glucose, insulin and adiponectin were measured in fasted mice. Hypothalamic TLR4 pathway proteins, serotonin receptors 1B and 2C and serotonin transporter were analyzed by Western blotting or enzyme-linked immunosorbent assay. A second set of animals was used to measure food intake in response to fluoxetine, a selective serotonin reuptake inhibitor. Mice fed with HFD had increased body weight and mass of fat depots, impaired oral glucose tolerance, elevated glucose and insulin and decreased adiponectin serum levels. TLR4, IκB-α, nuclear factor κB p50 and interleukin 6 were increased by HFD. Concomitant GTE treatment ameliorated these parameters. The serotoninergic system remained functional after HFD treatment despite a few alterations in protein content of serotonin receptors 1B and 2C and serotonin transporter. In summary, the GTE attenuated the deleterious effects of the HFD investigated in this study, partially due to reduced hypothalamic inflammation.