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Objective The obesogenic food environment facilitates access to multiple palatable foods. Exendin-4 (EX4) is a glucagon-like peptide 1 receptor (GLP1R) agonist that inhibits food intake and has been proposed as an obesity therapy. This study tested whether the composition of the food environment and experience with palatable foods modulate the effects of EX4 on food intake and reward. Methods Mice fed a cafeteria (CAF) or control diet were tested for the anorectic effects of EX4 when simultaneously offered foods of varying individual preference and in a conditioned place preference (CPP) test for chocolate. Plasma glucagon-like peptide 1 (GLP1) and hypothalamic GLP1R mRNA were analyzed post mortem. Results Mice fed a CAF diet developed individual food preference patterns. Offering mice either novel or highly preferred foods decreased the potency of EX4 to inhibit food intake compared to low preference foods or chow. Compared to the control diet, CAF diet intake blocked the decrease in chocolate CPP caused by EX4 and decreased the expression of hypothalamic GLP1R mRNA without altering the plasma GLP1 concentration. Conclusions The composition of the food environment, food preference, and experience modulate the ability of EX4 to inhibit food intake and reward. These data highlight the significance of modeling the complexity of the human food environment in preclinical obesity studies.

Prostate cancer (PCa) is a disease of increasing medical significance worldwide. In developed countries, PCa is the most common non-skin cancer in men, and one of the leading causes of cancer-related deaths. Exercise is one of the environmental factors that have been shown to influence cancer risk. Moreover, systemic reviews and meta-analysis have suggested that total physical activity is related to a decrease in the risk of developing PCa. In addition, epidemiological studies have shown that exercise, after diagnosis, has benefits regarding PCa development, and positive outcome in patients under treatment. The standard treatment for locally advanced or metastatic PCa is Androgen deprivation therapy (ADT). ADT produces diverse side effects, including loss of libido, changes in body composition (increase abdominal fat), and reduced muscle mass, and muscle tone. Analysis of numerous research publications showed that aerobic and/or resistance training improve patient's physical condition, such us, cardiorespiratory fitness, muscle strength, physical function, body composition, and fatigue. Therefore, exercise might counteract several ADT treatment-induced side effects. In addition of the aforementioned benefits, epidemiological, and in vitro studies have shown that exercise might decrease PCa development. Thus, physical activity might attenuate the risk of PCa and supervised exercise intervention might improve deleterious effects of cancer treatment, such as ADT side effects. This review article provides evidence indicating that exercise could complement, and potentiate, the current standard treatments for advanced PCa, probably by creating an unfavorable microenvironment that can negatively affect tumor development, and progression.

The obesogenic food environment facilitates access to multiple palatable foods. Exendin-4 (EX4) is a glucagon-like peptide 1 receptor (GLP1R) agonist that inhibits food intake and has been proposed as an obesity therapy. This study tested whether the composition of the food environment and experience with palatable foods modulate the effects of EX4 on food intake and reward.Mice fed a cafeteria (CAF) or control diet were tested for the anorectic effects of EX4 when simultaneously offered foods of varying individual preference and in a conditioned place preference (CPP) test for chocolate. Plasma glucagon-like peptide 1 (GLP1) and hypothalamic GLP1R mRNA were analyzed post mortem.Mice fed a CAF diet developed individual food preference patterns. Offering mice either novel or highly preferred foods decreased the potency of EX4 to inhibit food intake compared to low preference foods or chow. Compared to the control diet, CAF diet intake blocked the decrease in chocolate CPP caused by EX4 and decreased the expression of hypothalamic GLP1R mRNA without altering the plasma GLP1 concentration.The composition of the food environment, food preference, and experience modulate the ability of EX4 to inhibit food intake and reward. These data highlight the significance of modeling the complexity of the human food environment in preclinical obesity studies.

One of the major goals in the research of autoimmune diseases is to develop specific therapies to regulate the expression and function of gene products that could contribute to restoring tolerance to self-constituents and replace conventional systemic immunosuppression, which is associated with important undesired side effects. Although significant progress has been made on the understanding of the pathogenesis of autoimmunity, therapies for these ailments have not seen a change. During the last decade, different strategies such as pharmacologic or gene therapy modulation of heme oxygenase-1 (HO-1) and the administration of its metabolic product, carbon monoxide (CO), have been shown to display beneficial immunoregulatory and cytoprotective properties. In different experimental autoimmune conditions, such as Experimental autoimmune encephalomyelitis, type-1 diabetes and systemic lupus erythematosus, genetic or pharmacological modulation of HO-1, as well as delivery of CO have shown to ameliorate disease progression. Furthermore, it has been demonstrated that dendritic cell and monocyte function can be modulated by HO-1 and/or CO. In this article, recent data related to the immunoregulatory properties of HO-1/CO will be discussed, focusing on their potential therapeutic use to treat autoimmune diseases.

Introduction The clinical localization of primary cancers and sites of metastasis by positron emission tomography (PET) is based on the enhanced cellular uptake of 2-deoxy-2-[ 18 F]-fluoro-d-glucose (FDG). In prostate cancer (CaP), however, FDG-PET imaging has shown limited clinical applicability. This striking difference suggests that CaP cells utilise hexoses other than glucose, such as fructose, as the principal energy source. The purpose of this study was to determine whether or not fructose is a/the principal source of energy for CaP cells. Material and methods We determined the glucose and fructose concentration in serum from benign and CaP patients, the protein expression of Glut1, Glut5 and Glut9 and mRNA expression of Glut1, Glut5, Glut7, Glut9 and Glut11 in clinical specimens of benign and malignant prostate tissue using immunostaining and qRT-PCR. Moreover, mRNA and protein expression for the glucose transporters was analysed in vitro in benign (RWPE-1) and malignant (LNCaP, LNCaP-C4-2, DU-145, and PC3) CaP cell lines using qRT-PCR and western blot. Fructose and glucose uptake was measured in vitro in prostate cell lines using radiolabelled d-[U- 14 C]-fructose or 2-[1,2–3 hour]-deoxy-d-[ 3 H]-glucose, respectively. The effect of fructose and glucose on mitochondrial metabolism was analysed in prostate cell lines using seahorse analysis and the effect of fructose on tumour growth was analysed in vivo using a PC3 cell line xenograft model using immunosuppressed NSG mice. Results and discussions Fructose concentration was elevated in CaP patients compared to benign and no difference in glucose levels was observed. The expression of the fructose transporters, Glut5 and Glut9, was increased in CaP cell lines and in human CaP tissues compared to benign cell lines and benign prostate tissues, respectively. Glut1 expression, however, did not differ between benign and malignant human prostate cells. Transport assays demonstrated that CaP cell lines have a higher capacity to transport fructose compared to benign cell lines. However, glucose uptake was not altered between benign and malignant human prostate cell lines. ATP levels, basal and maximal respiration in bening and CaP cells were similar in the presence of fructose or glucose. Lastly, fructose was able to increase the growth rate, size and weight of the tumours in the NSG mice compared to controls (without fructose). Conclusion Our results indicate that fructose may represent an alternative energy source for CaP cells and may promote CaP tumour growth of CaP cells in vivo .

Introduction PET-scanning can detect primary tumours relaying on their high glucose uptake ability through overexpression of the glucose transporter Glut-1. However, this method has shown limited clinical applicability for prostate cancer (PCa) diagnosis, suggesting that PCa cells do not use glucose as its primary source of energy. Preliminary data from our laboratory has shown overexpression of the fructose transporter Glut-5 in PCa cell lines and in clinical specimens of PCa, which suggest that fructose could play an important role in PCa biology. Material and methods We analysed the effect of fructose on aggressiveness and metabolic reprogramming in benign prostate epithelial and PCa cell lines. Cells were incubated with glucose or fructose in the media for 24, 48, and 72 hour and then we evaluated: 1) the proliferative rate of benign and PCa cells, 2) the invasion and migration capacity of PCa cells, and 3) the mRNA levels of the enzymes involved in glycolysis, pentose phosphate and de novo lipogenesis pathways using real-time PCR in PCa cells. The effect of fructose on tumour growth was analysed by a PC3 cell line xenograft in immunosuppressed NSG mice. 15% fructose was added to the drinking water for 8 weeks. Tumour weight and the expression of glycolytic enzymes by qPCR was evaluated with respect to the control (water without additives). Results and discussions PCa cells incubated with fructose or glucose, showed similar proliferative rate, invasion and migration capacities. However, fructose evokes a different expression profile of the enzymes involve in glycolysis, pentose phosphate and de novo lipogenesis pathways. Fructose promotes tumour growth of PC3 cells in the NSG mice. Conclusion Our data suggest that fructose could play an important role in PCa pathophysiology, promoting proliferation and migration of PCa cells in vitro , and increasing tumour growth in vivo thanks to a reprogram in their metabolism that allows PCa cells to use fructose as effectively as glucose.