Obesity and type 2 diabetes are characterized by subclinical inflammatory process. Changes in composition or modulation of the gut microbiota may play an important role in the obesity-associated ...inflammatory process. In the current study, we evaluated the effects of probiotics (Lactobacillus rhamnosus, L. acidophilus and Bifidobacterium bifidumi) on gut microbiota, changes in permeability, and insulin sensitivity and signaling in high-fat diet and control animals. More importantly, we investigated the effects of these gut modulations on hypothalamic control of food intake, and insulin and leptin signaling. Swiss mice were submitted to a high-fat diet (HFD) with probiotics or pair-feeding for 5 weeks. Metagenome analyses were performed on DNA samples from mouse feces. Blood was drawn to determine levels of glucose, insulin, LPS, cytokines and GLP-1. Liver, muscle, ileum and hypothalamus tissue proteins were analyzed by Western blotting and real-time polymerase chain reaction. In addition, liver and adipose tissues were analyzed using histology and immunohistochemistry. The HFD induced huge alterations in gut microbiota accompanied by increased intestinal permeability, LPS translocation and systemic low-grade inflammation, resulting in decreased glucose tolerance and hyperphagic behavior. All these obesity-related features were reversed by changes in the gut microbiota profile induced by probiotics. Probiotics also induced an improvement in hypothalamic insulin and leptin resistance. Our data demonstrate that the intestinal microbiome is a key modulator of inflammatory and metabolic pathways in both peripheral and central tissues. These findings shed light on probiotics as an important tool to prevent and treat patients with obesity and insulin resistance.
In obesity, insulin resistance (IR) and diabetes, there are proteins and hormones that may lead to the discovery of promising biomarkers and treatments for these metabolic disorders. For example, ...these molecules may impair the insulin signaling pathway or provide protection against IR. Thus, identifying proteins that are upregulated in IR states is relevant to the diagnosis and treatment of the associated disorders. It is becoming clear that hepatocyte growth factor (HGF) is an important component of the pathophysiology of IR, with increased levels in most common IR conditions, including obesity. HGF has a role in the metabolic flux of glucose in different insulin sensitive cell types; plays a key role in β-cell homeostasis; and is capable of modulating the inflammatory response. In this review, we discuss how, and to what extent HGF contributes to IR and diabetes pathophysiology, as well as its role in cancer which is more prevalent in obesity and diabetes. Based on the current literature and knowledge, it is clear that HGF plays a central role in these metabolic disorders. Thus, HGF levels could be employed as a biomarker for disease status/progression, and HGF/c-Met signaling pathway modulators could effectively regulate IR and treat diabetes.
Insulin resistance is present in obesity and in type 2 diabetes and is associated with islet cell hyperplasia and hyperinsulinemia, but the driving forces behind this compensatory mechanism are ...incompletely understood. Previous data have suggested the involvement of an unknown circulating insulin resistance-related β-cell growth factor. In this context, looking for candidates to be a circulating factor, we realized that hepatocyte growth factor (HGF) is a strong candidate as a link between insulin resistance and increased mass of islets/hyperinsulinemia. Our approach aimed to show a possible cause-effect relationship between increase in circulating HGF levels and compensatory islet hyperplasia/hyperinsulinemia by showing the strength of the association, whether or not is a dose-dependent response, the temporality, consistency, plausibility, and reversibility of the association. In this regard, our data showed: 1) a strong and consistent correlation between HGF and the compensatory mechanism in three animal models of insulin resistance; 2) HGF increases β-cell mass in a dose-dependent manner; 3) blocking HGF shuts down the compensatory mechanisms; and 4) an increase in HGF levels seems to precede the compensatory response associated with insulin resistance, indicating that these events occur in a sequential mode. Additionally, blockages of HGF receptor (Met) worsen the impaired insulin-induced insulin signaling in liver of diet-induced obesity rats. Overall, our data indicate that HGF is a growth factor playing a key role in islet mass increase and hyperinsulinemia in diet-induced obesity rats and suggest that the HGF-Met axis may have a role on insulin signaling in the liver.
Obesity and type 2 diabetes are characterized by insulin resistance, and the common basis of these events is a chronic and systemic inflammatory process marked by the activation of the c-Jun ...N-terminal kinase (JNK) and inhibitor-κB kinase (IKKβ)/nuclear factor-κB (NFκB) pathways, up-regulated cytokine synthesis, and endoplasmic reticulum dysfunction. The aim of this study was to evaluate the effects of diacerhein administration, an antiinflammatory drug that reduces the levels of inflammatory cytokines, on insulin sensitivity and signaling in diet-induced obese (DIO) mice. Swiss mice were fed with conventional chow (control group) or a high-fat diet (DIO group). Later, DIO mice were randomly subdivided into a new subgroup (DAR) that received 20 mg/kg diacerhein for 10 d. Western blotting was used to quantify the expression and phosphorylation of insulin receptor, insulin receptor substrate 1, and Akt and of inflammatory mediators that modulate insulin signaling in a negative manner (IKKβ, JNK, and inducible nitric oxide synthase). We show here, for the first time, that the administration of diacerhein in DIO mice improved endoplasmic reticulum stress, reduced JNK and IKKβ phosphorylation, and resulted in a marked improvement in fasting glucose, a decrease in macrophage infiltration in adipose tissue, and a reduced expression and activity of proinflammatory mediators accompanied by an improvement in the insulin signaling mainly in the liver and adipose tissue. Taken together, these results indicate that diacerhein treatment improves insulin sensitivity in obesity, mediated by the reversal of subclinical inflammation, and that this drug may be an alternative therapy for insulin resistance.
Objective: The double‐stranded RNA‐dependent protein kinase (PKR) was recently implicated in regulating molecular integration of nutrient‐ and pathogen‐sensing pathways in obese mice. However, its ...modulation in human tissues in situations of insulin resistance has not been investigated. The present study was performed to first determine the tissue expression and phosphorylation levels of PKR in the liver, muscle, and adipose tissue in obese humans, and also the modulation of this protein in the adipose tissue of obese patients after bariatric surgery.
Design and Methods: Eleven obese subjects who were scheduled to undergo Roux‐en‐Y Gastric Bypass Procedure participated in this study. Nine apparently healthy lean subjects as a control group were also included.
Results: Our data show that PKR is activated in liver, muscle, and adipose tissue of obese humans and, after bariatric surgery, there is a clear reduction in PKR activation accompanied by a decrease in protein kinase‐like endoplasmic reticulum kinase, c‐Jun N‐terminal kinase, inhibitor of kappa β kinase, and insulin receptor substrate‐1 serine 312 phosphorylation in subcutaneous adipose tissue from these patients.
Conclusion: Thus, it is proposed that PKR is an important mediator of obesity‐induced insulin resistance and a potential target for the therapy.
Objective
It has become clear that exercise may be a useful therapy in the insulin resistance treatment, as it has anti‐inflammatory effects and improves insulin sensitivity. However, it remains ...uncertain whether exercise affects the adipocytes or infiltrated macrophages. Thus, the aim was to investigate the effects of acute exercise on the inflammatory status and insulin signaling of the white adipose tissue (WAT) fractions (stromal‐vascular fraction SVF and adipocytes).
Design and Methods
The effect of acute swimming exercise was investigated on insulin sensitivity, insulin signaling, inflammatory pathways in the WAT fractions of high‐fat fed Wistar rats. Additionally, macrophage infiltration and polarization were analyzed in the WAT.
Results
Acute exercise can improve insulin signaling in WAT fractions, along with a phenotypic switch from M1‐ to M2‐macrophages in obese rats, as indicated by a marked increase in macrophage galactose‐type C‐type lectin 1‐positive cells in WAT was observed. Additionally, exercise promoted a reduction in circulating levels of lipopolysaccharide, and toll‐like receptor 4 activity along with TNF‐alpha, IL‐1‐beta and MCP‐1 mRNA levels in WAT fractions.
Conclusions
These data suggest that acute exercise improves insulin signaling in the WAT, at least in part by inducing macrophage polarization toward the M2‐state.
Industrial egg residue (IER) possesses substantial concentrations of calcium and crude protein. The objective of this study was to measure the digestibility and performance of broilers when IER was ...added to the feed. Four treatments were tested, which caused increasing replacement of calcitic limestone by IER (0, 35, 70 and 100%) during a 42-day production cycle. First, total bird excreta were collected from broilers with and without IER, and we determined dry matter digestibility, apparent metabolizable energy (AME), calcium, and nitrogen retention. The IER presented 7.5% of crude protein, 31% of calcium, 209 kcal/kg of AME and the digestibility coefficients for dry matter, crude protein, and calcium were calculated at 83.95%, 86.20%, and 67%, respectively. After the digestibility test, the effects of IER on performance, carcass and meat yield were evaluated. No significant differences between the treatments were found in terms of performance (weight gain, feed conversion, consumption, and mortality), and no differences were found in terms of carcass or meat yield. A linear decrease in the percentage of abdominal fat was observed with increasing inclusion of IER in feed. These findings suggest that IER can totally replace limestone (calcium carbonate) in broiler diets.
Catalysts of AlMCM-48 with different Si/Al molar rations were synthesized by modified hydrothermal method with respect to previous works. As a consequence, the materials showed different porous ...structures making them of high adsorption capacities and high efficiency to high-density polyethylene (HDPE). Samples synthesized with various Si/Al molar ratios were characterized by X-ray diffraction (XRD), nitrogen adsorption at – 196 °C, scanning electron microscope (SEM), transmission electron microscope (TEM), Fourier transform infrared (FTIR) and dispersive energy X-ray spectrometry (EDX). Characterization results suggested the presence of tetrahedral Al species on AlMCM-48(x), giving highly ordered materials that exhibit thermal stability. It is important to highlight that the use pseudoboehmite as a promising Al source for the synthesis of this type of molecular sieves, leading to materials with slight morphological differences due to the formation of interconnected particles spherical. The catalytic performance showed that the high-density polyethylene (HDPE) degradation reaction occurs in complex reaction steps in the heating rates 5, 10 and 20 °C min
−1
. The pore diameters of the catalysts influence the degradation process under non-isothermal condition. Furthermore, on the conditions studied, the AlMCM-48(x) catalysts exhibited high conversion values and play important roles in the decrease of HDPE degradation temperature, potentially leading to an efficient process in terms of energy expenditure.
A simple, easy, and safe procedure aiming to improve liver regeneration could be of great clinical benefit in critical situations such as major hepatectomy, trauma, or hemorrhage. Low-power laser ...irradiation (LPLI) has come into a wide range of use in clinical practice by inducing regeneration in healthy and injured tissues. However, the effect of LPLI on the process of liver regeneration, especially those related to the molecular mechanisms, is not fully understood. Thus, the aim of the present study was to investigate the main molecular mechanisms involved in liver regeneration of partially hepatectomized rats exposed to LPLI. We used Wistar male rats, which had their remaining liver irradiated or not with LPLI (wavelength of 632.8 nm and fluence of 65 mW/cm
2
) for 15 min after a 70 % hepatectomy. We subsequently investigated hepatocyte growth factor (HGF), Met, Akt, and Erk 1/2 signaling pathways through protein expression and phosphorylation analyses along with cell proliferation (proliferating cell nuclear antigen (PCNA) and Ki-67) using immunoblotting and histological studies. Our results show that LPLI can improve liver regeneration as shown by increased HGF protein expression and the phosphorylation levels of Met, Akt, and Erk 1/2 accompanied by higher levels of the PCNA and Ki-67 protein in the remnant livers. In summary, our results suggest that LPLI may play a clinical role as a simple, fast, and easy-to-perform strategy in order to enhance the liver regenerative capacity of a small liver remnant after hepatectomy.
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