Effects of different doses of glucose and fructose on central metabolic pathways and intercellular wireless communication networks in humans

Fructose and glucose are often widely used in food processing and may contribute to many metabolic diseases.To observe the effects of different doses of glucose and fructose on human metabolism and cellular communication,volunteers were given low,medium,and high doses of glucose and fructose.Serum cytokines,glucose,lactate,nicotinamide adenine dinucleotide(NADH)and metabolic enzymes were assayed,and central carbon metabolic pathway networks and cytokine communication networks were constructed.The results showed that the glucose and fructose groups basically maintained the trend of decreasing catabolism and increasing anabolism with increasing dose.Compared with glucose,low-dose fructose decreased catabolism and increased anabolism,significantly enhanced the expression of the inflammatory cytokine interferon-γ(IFN-γ),macrophage-derived chemokine(MDC),induced protein-10(IP-10),and eotaxin,and significantly reduced the activity of isocitrate dehydrogenase(ICDH)and pyruvate dehydrogenase complexes(PDHC).Both medium and high doses of fructose increase catabolism and anabolism,and there are more cytokines and enzymes with significant changes.Furthermore,multiple cytokines and enzymes show strong relevance to metabolic regulation by altering the transcription and expression of enzymes in central carbon metabolic pathways.Therefore,excessive intake of fructose should be reduced to avoid excessive inflammatory responses,allergic reactions and autoimmune diseases.

How functional foods play critical roles in human health

How do functional foods affect human health?To answer this question it is important to understand what happens when food is digested and taken up by the gastrointestinal(GI)tract.The gut is a selective nutrient absorption system and the most important signal transduction and information exchange system within the body.It acts as a signal transducer,a neuroendocrine sensor,and an immunological recognition and presentation system.It is also a complex information exchange system comprising a number of signaling networks involving GI cells and cells immobilized in organs or transported in blood.The bioactivity of functional foods in vivo may be due to their effects on such networks,but this raises the question of what signaling pathways are used by non-nutrients that cannot be absorbed by the gut.The purpose of this review is to describe intestinal nutrient transportation,identify a number of widely expressed receptors and signal transduction pathways,and outline our current understanding of the mechanisms involved in health and disease.At the end of the review,a method for developing a cell communication network is described.This network is convenient for investigating the effects of oral administration of experimental medicines,drugs,or functional foods on cytokines of interest.Because cytokines and chemokines are transported via the circulatory system,a simple 2–3 mL blood sample from a volunteer is a rich source of information.This method may become the gold standard for evaluating the effects of functional foods or medicines in vivo.©2012 Production and hosting by Elsevier B.V.on behalf of Beijing Academy of Food Sciences.

Effect of casein glycomacropeptide on subunit p65 of nuclear transcription factor-B in lipopolysaccharide-stimulated human colorectal tumor HT-29 cells

Objective:The effect of casein glycomacropeptide(CGMP)on the expression of NF-B subunit p65 in human colorectal cancer HT-29 cells induced by lipopolysaccharide(LPS)was investigated to explore the therapeutic efficacy of CGMP for human colorectal cancer.Methods:HT-29 cells cultured in 96-well plates were stimulated with LPS for 30 min at the concentrations of 0,0.001,0.01,0.1,1 and 10g/mL.After stimulation,the expression of p65 in HT-29 cells was evaluated by immunofluorescence method.Similarly,HT-29 cells were incubated with 0,0.001,0.01,0.1,1,10 and 100g/mL CGMP for 24 h at the optimal LPS concentration.After treatment with CGMP under the incubation with optimal LPS concentration for 30 min,the protein expression of p65 was analyzed by Western blotting.The optimum culture time was evaluated by incubating HT-29 cells with the optimal CGMP concentration for 6,12,24,48 and 72 h.Results:NF-B-p65 revealed that the highest protein expression was achieved with 1g/mL LPS treatment.Meanwhile,CGMP could inhibit the protein expression of NF-B-p65 in LPS-stimulated HT-29 cells,and the optimal inhibitory effect was observed at a CGMP concentration of 0.01g/mL with 48 h incubation.Conclusion:CGMP can regulate NF-B signaling pathway through inhibiting the expression of its subunit p65,which is beneficial for the further improvement of human colorectal cancer treatment.

Energy intake,metabolic homeostasis,and human health

The energy substances(mainly carbohydrates and fats)are the basis and guarantee of life activity,especially the oxidative phosphorylation for energy supply.However,excessive absorption and accumulation of these substances can lead to metabolic diseases such as obesity,hyperlipidemia,diabetes,and cancers.A large amount of studies demonstrate that G protein-coupled receptors(GPCRs)play a key role in identification and absorption of energy substances,and the signaling network of nerves,immune,and endocrine regulates their storage and utilization.The gastrointestinal mucus layer not only identifies these substances through identification in diet components but also transfers immune,metabolic,and endocrine signals of hormones,cytokines,and chemokines by promoting interactions between receptors and ligands.These signaling molecules are transferred to corresponding organs,tissues,and cells by the circulatory system,and cell activity is regulated by amplifying of cell signals that constitute the wireless communication network among cells in the body.Absorption,accumulation,and utilization of energy substances in the body obey the law of energy conservation.Energy is stored in the form of fat,and meets the demand of body via two coupled mechanisms:catabolism and oxidative phosphorylation.Under normal physiological conditions,fat consumption involves ketone body metabolism through the circulatory system and glucose consumption requires blood lactic acid cycle.Accumulation of excessive energy leads to the abnormal activation of mammalian target of rapamycin(mTOR),thus promoting the excretion of glucose or glycogen in the form of blood glucose and urine glucose.Alternatively,the body cancels the intercellular contact inhibition and promotes cell proliferation to induce carcinogenesis,which can induce the consumption of large amounts of glucose.Intercellular communication is performed by signaling molecules via sensing,absorption,accumulation,and utilization of energy substances,and anabolism and catabolism are controlled by the central metabolic pathway.Therefore,slower catabolism will result in longer life expectancy,whereas faster catabolism results in shorter life expectancy.Energy substances in diet influence the balance between energy and metabolism in the body through the sensing function of the gastrointestinal system at two levels:cellular communication network and metabolic network.The present review of studies aims to strengthen our knowledge on cellular communication and metabolic networks to offer a dietary guidance on the metabolism and communication role of various foods.

Effects of casein glycomacropeptide on the early development of primary colorectal cancer in rats

In this paper,we utilized dimethylhydrazine(DMH)-induced colorectal cancer(CC)model rats to explore the effects of casein glycomacropeptide(CGMP)on colorectal cancer.Rats with CC were orally administrated with 10,50,or 100 mg/kg bw d CGMP,or the same volume of phosphatebuffered saline for 15 weeks.The total numbers of aberrant crypt foci(ACF)and crypts per focus in colon were scored using a light microscope at low magnification after the colon was stained with methylene blue solutions.The methylation level of DNA extracted from colon was detected using methylation-specific PCR.The expression of p16 and mucin 2(MUC2)proteins were measured by immunohistochemistry.The results showed that although ACF were found in rats treated with CGMP,their number was significantly decreased compared to that of model rats.In addition,methylation and expression levels of p16 and MUC2 were also inhibited by CGMP,which were more obvious in rats treated with 50 mg/kg bw d CGMP.In conclusion,CGMP has potential application as nutritional therapy for preventing colorectal cancer.©2013 Beijing Academy of Food Sciences.Production and hosting by Elsevier B.V.All rights reserved.

Remodeling of the ryanodine receptor isoform 1 channel regulates the sweet and umami taste perception of Rattus norvegicus

Sweet and umami tastes are elicited by sweet and umami receptors on the tongue and palate epithelium,respectively.However,the molecular machinery allowing the taste reaction remains incompletely understood.Through a phosphoproteomic approach,we identified the key proteins that trigger taste mechanisms based on phosphorylation cascades.Ryanodine receptor isoform 1(RYR1)was further verified by sensory and behavioral assays.We propose a model of RYR1-mediated sweet/umami signaling in which the RYR1 channel,which mediates Ca^(2+)release from the endoplasmic reticulum,is closed by dephosphorylation in bud tissue after sweet/umami treatment.The alteration in Ca^(2+)content in the cytosol induces transient membrane depolarization and generates a cell current for taste signal transduction.We demonstrate that RYR1 is a new channel involved in the regulation of sweet/umami signal transduction and propose a“metabolic clock”notion based on sweet/umami sensing.Our study provides a valuable foundation for a system-level understanding of the taste perception mechanism.