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Editorial

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3 pages, 158 KiB

Open AccessEditorial

Bioactivity of Inositol Phosphates

by Ivana Vucenik

Molecules 2021, 26(16), 5042; https://doi.org/10.3390/molecules26165042 - 20 Aug 2021

Cited by 8 | Viewed by 2245

Abstract

Inositol phosphates (IPs) are a huge and complex family of biomolecules, important in regulating vital cellular functions, signal transduction, energy transmission, and ion channels physiology and serving as structural components of cell membranes [...] Full article

(This article belongs to the Special Issue Bioactivity of Inositol Phosphates)

Research

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12 pages, 747 KiB

Open AccessArticle

Phytic Acid Protects from Oxidative Stress Induced by Iron-Overload and High-Fat Diets in ß2-Microglobulin Knockout Mice

by Sixtus Aguree, Ling Guo and Manju B. Reddy

Molecules 2020, 25(22), 5331; https://doi.org/10.3390/molecules25225331 - 15 Nov 2020

Cited by 8 | Viewed by 2520

Abstract

The objective of this study was to examine the protective effect of phytic acid (PA) in reducing oxidative stress in an animal model for human hereditary hemochromatosis (HH) fed high-fat diets. Sixty-four ß2 microglobulin knockout (β2m KO) mice were randomly assigned to three [...] Read more.

The objective of this study was to examine the protective effect of phytic acid (PA) in reducing oxidative stress in an animal model for human hereditary hemochromatosis (HH) fed high-fat diets. Sixty-four ß2 microglobulin knockout (β2m KO) mice were randomly assigned to three treatments by feeding: control (basal), atherogenic (AT), and polyunsaturated fatty acid (PUFA) diets. One-half of the mice in each treatment group were fed 2% (wt/wt) PA. The ß2m+/+ mice (wild type (WT)) were fed a basal diet. All seven groups were fed for 10 weeks with a 50-ppm iron-containing diet (AIN-93G). Free iron and lipids were measured in serum samples. Nonheme iron, thiobarbituric acid-reactive substances (TBARS), superoxide dismutase (SOD), and catalase concentrations were measured in the liver tissue. Nonheme iron concentration in ß2m KO mice (on the basal diet) was 20× higher (p < 0.0001) than in the WT mice. Compared to the WT mice, ß2m KO mice had a significantly higher concentration of free iron in the serum (p < 0.0001), six-fold higher hepatic TBARs (p < 0.0001), and 18% lower hepatic SOD level. When PA was added to the β2m KO basal diet, a reduction (26 to 50%) of iron concentration was seen in the liver and heart. The addition of PA also significantly reduced TBARs in all three dietary groups of the iron-overloaded group, but most effectively in the control group. An increase in SOD concentration was seen only in the PUFA group, but serum triacylglycerol (TG) concentration was reduced in both dietary fat groups. In conclusion, our results suggest that PA protects against oxidative stress-induced by genetic iron overload alone or when fed high fat. Full article

(This article belongs to the Special Issue Bioactivity of Inositol Phosphates)

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16 pages, 2502 KiB

Open AccessArticle

Regulation of MicroRNA-155 and Its Related Genes Expression by Inositol Hexaphosphate in Colon Cancer Cells

by Małgorzata Kapral, Joanna Wawszczyk and Ludmiła Węglarz

Molecules 2019, 24(22), 4153; https://doi.org/10.3390/molecules24224153 - 16 Nov 2019

Cited by 20 | Viewed by 3485

Abstract

Inositol hexaphosphate (IP6), a natural dietary component, has been found as an antitumor agent by stimulating apoptosis and inhibiting cancer cell proliferation, their migration, and metastasis in diverse cancers including colon cancer. However, molecular mechanisms of its action have not been well understood. [...] Read more.

Inositol hexaphosphate (IP6), a natural dietary component, has been found as an antitumor agent by stimulating apoptosis and inhibiting cancer cell proliferation, their migration, and metastasis in diverse cancers including colon cancer. However, molecular mechanisms of its action have not been well understood. In recent years, microRNAs (miRNAs) have been reported to play important roles in a broad range of biologic processes, such as cell growth, proliferation, apoptosis, or autophagy. These small noncoding molecules regulate post-transcriptional expression of targets genes via degradation of transcript or inhibition of protein synthesis. Aberrant expression and/or dysregulation of miRNAs have been characterized during tumor development and progression, thus, they are potential molecular targets for cancer prevention. The aim of this study was to investigate the effect of IP6 on the miRNAs expression profile in Caco-2 colon cancer cells. 84 miRNAs were analyzed in Caco-2 cells treated with 2.5 mM and 5 mM IP6 by the use of PCR (Polymerase Chain Reaction) array. The effect of 5 mM IP6 on selected potential miR-155 targets was determined by real-time (RT)-qPCR and ELISA (quantitative Polymerase Chain Reaction and Enzyme-Linked Immunosorbent Assay )method. The results indicated alteration in the specific 10 miRNA expression in human colon cancer cells following their treatment with 5 mM IP6. It down-regulated 8 miRNAs (miR-155, miR-210, miR-144, miR-194, miR-26b, miR-126, miR-302c, and miR-29a) and up-regulated 2 miRNAs (miR-223 and miR-196b). In silico analysis revealed that FOXO3a, HIF-1α, and ELK3 mRNAs are those of predicted targets of miR-155. IP6 at the concentration of 5 mM markedly induced FOXO3a and HIF-1a genes’ expression at both mRNA and protein level and decreased the amount of ELK3 mRNA as well as protein concentration in comparison to the control. In conclusion, the present study indicates that one of the mechanisms of antitumor potential of IP6 is down-regulation of the miR-155 expression in human colon cancer cells. Moreover, the expression of genes that are targeted by miRNA are also modulated by IP6. Full article

(This article belongs to the Special Issue Bioactivity of Inositol Phosphates)

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Review

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28 pages, 1361 KiB

Open AccessReview

Analytical Methods for Determination of Phytic Acid and Other Inositol Phosphates: A Review

by Gregor Marolt and Mitja Kolar

Molecules 2021, 26(1), 174; https://doi.org/10.3390/molecules26010174 - 31 Dec 2020

Cited by 45 | Viewed by 11860

Abstract

From the early precipitation-based techniques, introduced more than a century ago, to the latest development of enzymatic bio- and nano-sensor applications, the analysis of phytic acid and/or other inositol phosphates has never been a straightforward analytical task. Due to the biomedical importance, such [...] Read more.

From the early precipitation-based techniques, introduced more than a century ago, to the latest development of enzymatic bio- and nano-sensor applications, the analysis of phytic acid and/or other inositol phosphates has never been a straightforward analytical task. Due to the biomedical importance, such as antinutritional, antioxidant and anticancer effects, several types of methodologies were investigated over the years to develop a reliable determination of these intriguing analytes in many types of biological samples; from various foodstuffs to living cell organisms. The main aim of the present work was to critically overview the development of the most relevant analytical principles, separation and detection methods that have been applied in order to overcome the difficulties with specific chemical properties of inositol phosphates, their interferences, absence of characteristic signal (e.g., absorbance), and strong binding interactions with (multivalent) metals and other biological molecules present in the sample matrix. A systematical and chronological review of the applied methodology and the detection system is given, ranging from the very beginnings of the classical gravimetric and titrimetric analysis, through the potentiometric titrations, chromatographic and electrophoretic separation techniques, to the use of spectroscopic methods and of the recently reported fluorescence and voltammetric bio- and nano-sensors. Full article

(This article belongs to the Special Issue Bioactivity of Inositol Phosphates)

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11 pages, 592 KiB

Open AccessReview

Overview of Inositol and Inositol Phosphates on Chemoprevention of Colitis-Induced Carcinogenesis

by Samuel E. Weinberg, Le Yu Sun, Allison L. Yang, Jie Liao and Guang Yu Yang

Molecules 2021, 26(1), 31; https://doi.org/10.3390/molecules26010031 - 23 Dec 2020

Cited by 15 | Viewed by 4266

Abstract

Chronic inflammation is one of the most common and well-recognized risk factors for human cancer, including colon cancer. Inflammatory bowel disease (IBD) is defined as a longstanding idiopathic chronic active inflammatory process in the colon, including ulcerative colitis and Crohn’s disease. Importantly, patients [...] Read more.

Chronic inflammation is one of the most common and well-recognized risk factors for human cancer, including colon cancer. Inflammatory bowel disease (IBD) is defined as a longstanding idiopathic chronic active inflammatory process in the colon, including ulcerative colitis and Crohn’s disease. Importantly, patients with IBD have a significantly increased risk for the development of colorectal carcinoma. Dietary inositol and its phosphates, as well as phospholipid derivatives, are well known to benefit human health in diverse pathologies including cancer prevention. Inositol phosphates including InsP₃, InsP₆, and other pyrophosphates, play important roles in cellular metabolic and signal transduction pathways involved in the control of cell proliferation, differentiation, RNA export, DNA repair, energy transduction, ATP regeneration, and numerous others. In the review, we highlight the biologic function and health effects of inositol and its phosphates including the nature and sources of these molecules, potential nutritional deficiencies, their biologic metabolism and function, and finally, their role in the prevention of colitis-induced carcinogenesis. Full article

(This article belongs to the Special Issue Bioactivity of Inositol Phosphates)

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13 pages, 243 KiB

Open AccessReview

Inositol Hexaphosphate (IP6) and Colon Cancer: From Concepts and First Experiments to Clinical Application

by Ivana Vucenik, Ana Druzijanic and Nikica Druzijanic

Molecules 2020, 25(24), 5931; https://doi.org/10.3390/molecules25245931 - 15 Dec 2020

Cited by 31 | Viewed by 9172

Abstract

Multiple human health-beneficial effects have been related to highly phosphorylated inositol hexaphosphate (IP6). This naturally occurring carbohydrate and its parent compound, myo-inositol (Ins), are abundantly present in plants, particularly in certain high-fiber diets, but also in mammalian cells, where they regulate important [...] Read more.

Multiple human health-beneficial effects have been related to highly phosphorylated inositol hexaphosphate (IP6). This naturally occurring carbohydrate and its parent compound, myo-inositol (Ins), are abundantly present in plants, particularly in certain high-fiber diets, but also in mammalian cells, where they regulate important cellular functions. However, the striking and broad-spectrum anticancer activity of IP6, consistently demonstrated in different experimental models, has been in a spotlight of the scientific community dealing with the nutrition and cancer during the last several decades. First experiments were performed in colon cancer 30 years ago. Since then, it has been shown that IP6 reduces cell proliferation, induces apoptosis and differentiation of malignant cells with reversion to normal phenotype, affecting several critical molecular targets. Enhanced immunity and antioxidant properties also contribute to the tumor cell destruction. Although Ins possesses a modest anticancer potential, the best anticancer results were obtained from the combination of IP6 + Ins. Here we review the first experimental steps in colon cancer, when concepts and hypotheses were put together almost without real knowledge and present clinical studies, that were initiated in colon cancer patients. Available as a dietary supplement, IP6 + Ins has been shown to enhance the anticancer effect of conventional chemotherapy, controls cancer metastases, and improves quality of life in cancer patients. Emerging clinical and still vast amount of experimental data suggest its role either as an adjuvant or as an “alternative” to current chemotherapy for cancer. Full article

(This article belongs to the Special Issue Bioactivity of Inositol Phosphates)

21 pages, 707 KiB

Open AccessReview

Inositols in PCOS

by Zdravko Kamenov and Antoaneta Gateva

Molecules 2020, 25(23), 5566; https://doi.org/10.3390/molecules25235566 - 27 Nov 2020

Cited by 55 | Viewed by 21056

Abstract

(1) Background: Myoinositol (MI) and D-chiro-inositol (DCI) are involved in a number of biochemical pathways within oocytes having a role in oocyte maturation, fertilization, implantation, and post-implantation development. Both inositols have a role in insulin signaling and hormonal synthesis in the ovaries. (2) [...] Read more.

(1) Background: Myoinositol (MI) and D-chiro-inositol (DCI) are involved in a number of biochemical pathways within oocytes having a role in oocyte maturation, fertilization, implantation, and post-implantation development. Both inositols have a role in insulin signaling and hormonal synthesis in the ovaries. (2) Methods: Literature search (with key words: inositols, myo-inositol, d-chiro-inositol, PCOS) was done in PubMed until Sept. 2020 and 197 articles were identified, of which 47 were of clinical trials (35 randomized controlled trials). (3) Results: Many studies have demonstrated that in patients with polycystic ovarian syndrome (PCOS) MI treatment improved ovarian function and fertility, decreased the severity of hyperandrogenism including acne and hirsutism, positively affected metabolic aspects, and modulated various hormonal parameters deeply involved in the reproductive axis function and ovulation. Thus treating with MI has become a novel method to ameliorate PCOS symptoms, improve spontaneous ovulation, or induce ovulation. The current review is focused on the effects of MI and DCI alone or in combination with other agents on the pathological features of PCOS with focus on insulin resistance and adverse metabolic outcomes. (4) Conclusions: The available clinical data suggest that MI, DCI, and their combination in physiological ratio 40:1 with or without other compound could be beneficial for improving metabolic, hormonal, and reproductive aspects of PCOS. Full article

(This article belongs to the Special Issue Bioactivity of Inositol Phosphates)

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13 pages, 1802 KiB

Open AccessReview

Signalling Properties of Inositol Polyphosphates

by Tania Maffucci and Marco Falasca

Molecules 2020, 25(22), 5281; https://doi.org/10.3390/molecules25225281 - 12 Nov 2020

Cited by 11 | Viewed by 3601

Abstract

Several studies have identified specific signalling functions for inositol polyphosphates (IPs) in different cell types and have led to the accumulation of new information regarding their cellular roles as well as new insights into their cellular production. These studies have revealed that interaction [...] Read more.

Several studies have identified specific signalling functions for inositol polyphosphates (IPs) in different cell types and have led to the accumulation of new information regarding their cellular roles as well as new insights into their cellular production. These studies have revealed that interaction of IPs with several proteins is critical for stabilization of protein complexes and for modulation of enzymatic activity. This has not only revealed their importance in regulation of several cellular processes but it has also highlighted the possibility of new pharmacological interventions in multiple diseases, including cancer. In this review, we describe some of the intracellular roles of IPs and we discuss the pharmacological opportunities that modulation of IPs levels can provide. Full article

(This article belongs to the Special Issue Bioactivity of Inositol Phosphates)

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18 pages, 1642 KiB

Open AccessFeature PaperReview

Role of Inositols and Inositol Phosphates in Energy Metabolism

by Saimai Chatree, Nanthaphop Thongmaen, Kwanchanit Tantivejkul, Chantacha Sitticharoon and Ivana Vucenik

Molecules 2020, 25(21), 5079; https://doi.org/10.3390/molecules25215079 - 1 Nov 2020

Cited by 98 | Viewed by 14866

Abstract

Recently, inositols, especially myo-inositol and inositol hexakisphosphate, also known as phytic acid or IP6, with their biological activities received much attention for their role in multiple health beneficial effects. Although their roles in cancer treatment and prevention have been extensively reported, interestingly, [...] Read more.

Recently, inositols, especially myo-inositol and inositol hexakisphosphate, also known as phytic acid or IP6, with their biological activities received much attention for their role in multiple health beneficial effects. Although their roles in cancer treatment and prevention have been extensively reported, interestingly, they may also have distinctive properties in energy metabolism and metabolic disorders. We review inositols and inositol phosphate metabolism in mammalian cells to establish their biological activities and highlight their potential roles in energy metabolism. These molecules are known to decrease insulin resistance, increase insulin sensitivity, and have diverse properties with importance from cell signaling to metabolism. Evidence showed that inositol phosphates might enhance the browning of white adipocytes and directly improve insulin sensitivity through adipocytes. In addition, inositol pyrophosphates containing high-energy phosphate bonds are considered in increasing cellular energetics. Despite all recent advances, many aspects of the bioactivity of inositol phosphates are still not clear, especially their effects on insulin resistance and alteration of metabolism, so more research is needed. Full article

(This article belongs to the Special Issue Bioactivity of Inositol Phosphates)

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20 pages, 1209 KiB

Open AccessReview

The Key Role of IP₆K: A Novel Target for Anticancer Treatments?

by Mirko Minini, Alice Senni, Vittorio Unfer and Mariano Bizzarri

Molecules 2020, 25(19), 4401; https://doi.org/10.3390/molecules25194401 - 25 Sep 2020

Cited by 13 | Viewed by 4385

Abstract

Inositol and its phosphate metabolites play a pivotal role in several biochemical pathways and gene expression regulation: inositol pyrophosphates (PP-IPs) have been increasingly appreciated as key signaling modulators. Fluctuations in their intracellular levels hugely impact the transfer of phosphates and the phosphorylation status [...] Read more.

Inositol and its phosphate metabolites play a pivotal role in several biochemical pathways and gene expression regulation: inositol pyrophosphates (PP-IPs) have been increasingly appreciated as key signaling modulators. Fluctuations in their intracellular levels hugely impact the transfer of phosphates and the phosphorylation status of several target proteins. Pharmacological modulation of the proteins associated with PP-IP activities has proved to be beneficial in various pathological settings. IP₇ has been extensively studied and found to play a key role in pathways associated with PP-IP activities. Three inositol hexakisphosphate kinase (IP₆K) isoforms regulate IP₇ synthesis in mammals. Genomic deletion or enzymic inhibition of IP₆K1 has been shown to reduce cell invasiveness and migration capacity, protecting against chemical-induced carcinogenesis. IP₆K1 could therefore be a useful target in anticancer treatment. Here, we summarize the current understanding that established IP₆K1 and the other IP₆K isoforms as possible targets for cancer therapy. However, it will be necessary to determine whether pharmacological inhibition of IP₆K is safe enough to begin clinical study. The development of safe and selective inhibitors of IP₆K isoforms is required to minimize undesirable effects. Full article

(This article belongs to the Special Issue Bioactivity of Inositol Phosphates)

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11 pages, 837 KiB

Open AccessReview

Inositol Pyrophosphate Pathways and Mechanisms: What Can We Learn from Plants?

by Caitlin Cridland and Glenda Gillaspy

Molecules 2020, 25(12), 2789; https://doi.org/10.3390/molecules25122789 - 17 Jun 2020

Cited by 21 | Viewed by 5233

Abstract

The ability of an organism to maintain homeostasis in changing conditions is crucial for growth and survival. Eukaryotes have developed complex signaling pathways to adapt to a readily changing environment, including the inositol phosphate (InsP) signaling pathway. In plants and humans the pyrophosphorylated [...] Read more.

The ability of an organism to maintain homeostasis in changing conditions is crucial for growth and survival. Eukaryotes have developed complex signaling pathways to adapt to a readily changing environment, including the inositol phosphate (InsP) signaling pathway. In plants and humans the pyrophosphorylated inositol molecules, inositol pyrophosphates (PP-InsPs), have been implicated in phosphate and energy sensing. PP-InsPs are synthesized from the phosphorylation of InsP₆, the most abundant InsP. The plant PP-InsP synthesis pathway is similar but distinct from that of the human, which may reflect differences in how molecules such as Ins(1,4,5)P₃ and InsP₆ function in plants vs. animals. In addition, PP-InsPs can potentially interact with several major signaling proteins in plants, suggesting PP-InsPs play unique signaling roles via binding to protein partners. In this review, we will compare the biosynthesis and role of PP-InsPs in animals and plants, focusing on three central themes: InsP₆ synthesis pathways, synthesis and regulation of the PP-InsPs, and function of a specific protein domain called the Syg1, Pho1, Xpr1 (SPX ) domain in binding PP-InsPs and regulating inorganic phosphate (Pi) sensing. This review will provide novel insights into the biosynthetic pathway and bioactivity of these key signaling molecules in plant and human systems. Full article

(This article belongs to the Special Issue Bioactivity of Inositol Phosphates)

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15 pages, 1513 KiB

Open AccessReview

Inositol Pyrophosphates: Signaling Molecules with Pleiotropic Actions in Mammals

by Seulgi Lee, Min-Gyu Kim, Hyoungjoon Ahn and Seyun Kim

Molecules 2020, 25(9), 2208; https://doi.org/10.3390/molecules25092208 - 8 May 2020

Cited by 39 | Viewed by 6006

Abstract

Inositol pyrophosphates (PP-IPs) such as 5-diphosphoinositol pentakisphosphate (5-IP7) are inositol metabolites containing high-energy phosphoanhydride bonds. Biosynthesis of PP-IPs is mediated by IP6 kinases (IP6Ks) and PPIP5 kinases (PPIP5Ks), which transfer phosphate to inositol hexakisphosphate (IP6). Pleiotropic actions of PP-IPs are involved in many [...] Read more.

Inositol pyrophosphates (PP-IPs) such as 5-diphosphoinositol pentakisphosphate (5-IP7) are inositol metabolites containing high-energy phosphoanhydride bonds. Biosynthesis of PP-IPs is mediated by IP6 kinases (IP6Ks) and PPIP5 kinases (PPIP5Ks), which transfer phosphate to inositol hexakisphosphate (IP6). Pleiotropic actions of PP-IPs are involved in many key biological processes, including growth, vesicular remodeling, and energy homeostasis. PP-IPs function to regulate their target proteins through allosteric interactions or protein pyrophosphorylation. This review summarizes the current understanding of how PP-IPs control mammalian cellular signaling networks in physiology and disease. Full article

(This article belongs to the Special Issue Bioactivity of Inositol Phosphates)

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15 pages, 728 KiB

Open AccessReview

New Frontiers for the Use of IP6 and Inositol Combination in Treating Diabetes Mellitus: A Review

by Felix O. Omoruyi, Dewayne Stennett, Shadae Foster and Lowell Dilworth

Molecules 2020, 25(7), 1720; https://doi.org/10.3390/molecules25071720 - 10 Apr 2020

Cited by 33 | Viewed by 9883

Abstract

Inositol, or myo-inositol, and associated analog molecules, including myo-inositol hexakisphosphate, are known to possess beneficial biomedical properties and are now being widely studied. The impact of these compounds in improving diabetic indices is significant, especially in light of the high cost of treating [...] Read more.

Inositol, or myo-inositol, and associated analog molecules, including myo-inositol hexakisphosphate, are known to possess beneficial biomedical properties and are now being widely studied. The impact of these compounds in improving diabetic indices is significant, especially in light of the high cost of treating diabetes mellitus and associated disorders globally. It is theorized that, within ten years, the global population of people with the disease will reach 578 million individuals, with the cost of care projected to be approximately 2.5 trillion dollars. Natural alternatives to pharmaceuticals are being sought, and this has led to studies involving inositol, and myo-inositol-hexakisphosphate, also referred to as IP6. It has been reported that IP6 can improve diabetic indices and regulate the activities of some metabolic enzymes involved in lipid and carbohydrate metabolism. Current research activities have been focusing on the mechanisms of action of inositol and IP6 in the amelioration of the indices of diabetes mellitus. We demonstrated that an IP6 and inositol combination supplement may regulate insulin secretion, modulate serum leptin concentrations, food intake, and associated weight gain, which may be beneficial in both prediabetic and diabetic states. The supplement attenuates vascular damage by reducing red cell distribution width. Serum HDL is increased while serum triglycerides tend to decrease with consumption of the combination supplement, perhaps due to the modulation of lipogenesis involving reduced serum lipase activity. We also noted increased fecal lipid output following combination supplement consumption. Importantly, liver function was found to be preserved. Concurrently, serum reactive oxygen species production was reduced, indicating that inositol and IP6 supplement consumption may reduce free radical damage to tissues and organs as well as serum lipids and blood glucose by preserving liver function. This review provides an overview of the findings associated with inositol and IP6 supplementation in the effective treatment of diabetes with a view to proposing the potential mechanisms of action. Full article

(This article belongs to the Special Issue Bioactivity of Inositol Phosphates)

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28 pages, 995 KiB

Open AccessReview

Targeting the Inositol Pyrophosphate Biosynthetic Enzymes in Metabolic Diseases

by Sandip Mukherjee, Jake Haubner and Anutosh Chakraborty

Molecules 2020, 25(6), 1403; https://doi.org/10.3390/molecules25061403 - 19 Mar 2020

Cited by 28 | Viewed by 5797

Abstract

In mammals, a family of three inositol hexakisphosphate kinases (IP6Ks) synthesizes the inositol pyrophosphate 5-IP7 from IP6. Genetic deletion of Ip6k1 protects mice from high fat diet induced obesity, insulin resistance and fatty liver. IP6K1 generated 5-IP7 promotes insulin secretion from pancreatic β-cells, [...] Read more.

In mammals, a family of three inositol hexakisphosphate kinases (IP6Ks) synthesizes the inositol pyrophosphate 5-IP7 from IP6. Genetic deletion of Ip6k1 protects mice from high fat diet induced obesity, insulin resistance and fatty liver. IP6K1 generated 5-IP7 promotes insulin secretion from pancreatic β-cells, whereas it reduces insulin signaling in metabolic tissues by inhibiting the protein kinase Akt. Thus, IP6K1 promotes high fat diet induced hyperinsulinemia and insulin resistance in mice while its deletion has the opposite effects. IP6K1 also promotes fat accumulation in the adipose tissue by inhibiting the protein kinase AMPK mediated energy expenditure. Genetic deletion of Ip6k3 protects mice from age induced fat accumulation and insulin resistance. Accordingly, the pan IP6K inhibitor TNP [N2-(m-trifluorobenzyl), N6-(p-nitrobenzyl)purine] ameliorates obesity, insulin resistance and fatty liver in diet induced obese mice by improving Akt and AMPK mediated insulin sensitivity and energy expenditure. TNP also protects mice from bone loss, myocardial infarction and ischemia reperfusion injury. Thus, the IP6K pathway is a potential target in obesity and other metabolic diseases. Here, we summarize the studies that established IP6Ks as a potential target in metabolic diseases. Further studies will reveal whether inhibition of this pathway has similar pleiotropic benefits on metabolic health of humans. Full article

(This article belongs to the Special Issue Bioactivity of Inositol Phosphates)

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9 pages, 561 KiB

Open AccessReview

Key Aspects of Myo-Inositol Hexaphosphate (Phytate) and Pathological Calcifications

by Felix Grases and Antonia Costa-Bauza

Molecules 2019, 24(24), 4434; https://doi.org/10.3390/molecules24244434 - 4 Dec 2019

Cited by 35 | Viewed by 5903

Abstract

Phytate (myo-inositol hexaphosphate, InsP6) is an important component of seeds, legumes, nuts, and whole cereals. Although this molecule was discovered in 1855, its biological effects as an antinutrient was first described in 1940. The antinutrient effect of phytate results because it can decrease [...] Read more.

Phytate (myo-inositol hexaphosphate, InsP6) is an important component of seeds, legumes, nuts, and whole cereals. Although this molecule was discovered in 1855, its biological effects as an antinutrient was first described in 1940. The antinutrient effect of phytate results because it can decrease the bioavailability of important minerals under certain circumstances. However, during the past 30 years, researchers have identified many important health benefits of phytate. Thus, 150 years have elapsed since the discovery of phytate to the first descriptions of its beneficial effects. This long delay may be due to the difficulty in determining phytate in biological media, and because phytate dephosphorylation generates many derivatives (InsPs) that also have important biological functions. This paper describes the role of InsP6 in blocking the development of pathological calcifications. Thus, in vitro studies have shown that InsP6 and its hydrolysates (InsPs), as well as pyrophosphate, bisphosphonates, and other polyphosphates, have high capacity to inhibit calcium salt crystallization. Oral or topical administration of phytate in vivo significantly decreases the development of pathological calcifications, although the details of the underlying mechanism are uncertain. Moreover, oral or topical administration of InsP6 also leads to increased urinary excretion of mixtures of different InsPs; in the absence of InsP6 administration, only InsP2 occurs at detectable levels in urine. Full article

(This article belongs to the Special Issue Bioactivity of Inositol Phosphates)

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