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      Application of Inositol Hexaphosphate and Inositol in Dental Medicine: An Overview

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      Biomolecules
      MDPI AG

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          Abstract

          Phosphorylated inositol hexaphosphate (IP6) is a naturally occurring carbohydrate, and its parent compound, myoinositol (Ins), is abundantly present in plants, particularly in certain high-fiber diets, but also in mammalian cells, where they regulate essential cellular functions. IP6 has profound modulation effects on macrophages, which warrants further research on the therapeutic benefits of IP6 for inflammatory diseases. Here, we review IP6 as a promising compound that has the potential to be used in various areas of dentistry, including endodontics, restorative dentistry, implantology, and oral hygiene products, due to its unique structure and characteristic properties. Available as a dietary supplement, IP6 + Ins has been shown to enhance the anti-inflammatory effect associated with preventing and suppressing the progression of chronic dental inflammatory diseases. IP6 in dentistry is now substantial, and this narrative review presents and discusses the different applications proposed in the literature and gives insights into future use of IP6 in the fields of orthodontics, periodontics, implants, and pediatric dentistry.

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          Most cited references33

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          Phytate in foods and significance for humans: food sources, intake, processing, bioavailability, protective role and analysis.

          The article gives an overview of phytic acid in food and of its significance for human nutrition. It summarises phytate sources in foods and discusses problems of phytic acid/phytate contents of food tables. Data on phytic acid intake are evaluated and daily phytic acid intake depending on food habits is assessed. Degradation of phytate during gastro-intestinal passage is summarised, the mechanism of phytate interacting with minerals and trace elements in the gastro-intestinal chyme described and the pathway of inositol phosphate hydrolysis in the gut presented. The present knowledge of phytate absorption is summarised and discussed. Effects of phytate on mineral and trace element bioavailability are reported and phytate degradation during processing and storage is described. Beneficial activities of dietary phytate such as its effects on calcification and kidney stone formation and on lowering blood glucose and lipids are reported. The antioxidative property of phytic acid and its potentional anticancerogenic activities are briefly surveyed. Development of the analysis of phytic acid and other inositol phosphates is described, problems of inositol phosphate determination and detection discussed and the need for standardisation of phytic acid analysis in foods argued.
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            Adipocyte-specific deletion of Ip6k1 reduces diet-induced obesity by enhancing AMPK-mediated thermogenesis.

            Enhancing energy expenditure (EE) is an attractive strategy to combat obesity and diabetes. Global deletion of Ip6k1 protects mice from diet-induced obesity (DIO) and insulin resistance, but the tissue-specific mechanism by which IP6K1 regulates body weight is unknown. Here, we have demonstrated that IP6K1 regulates fat accumulation by modulating AMPK-mediated adipocyte energy metabolism. Cold exposure led to downregulation of Ip6k1 in murine inguinal and retroperitoneal white adipose tissue (IWAT and RWAT) depots. Adipocyte-specific deletion of Ip6k1 (AdKO) enhanced thermogenic EE, which protected mice from high-fat diet-induced weight gain at ambient temperature (23°C), but not at thermoneutral temperature (30°C). AdKO-induced increases in thermogenesis also protected mice from cold-induced decreases in body temperature. UCP1, PGC1α, and other markers of browning and thermogenesis were elevated in IWAT and RWAT of AdKO mice. Cold-induced activation of sympathetic signaling was unaltered, whereas AMPK was enhanced, in AdKO IWAT. Moreover, beige adipocytes from AdKO IWAT displayed enhanced browning, which was diminished by AMPK depletion. Furthermore, we determined that IP6 and IP6K1 differentially regulate upstream kinase-mediated AMPK stimulatory phosphorylation in vitro. Finally, treating mildly obese mice with the IP6K inhibitor TNP enhanced thermogenesis and inhibited progression of DIO. Thus, IP6K1 regulates energy metabolism via a mechanism that could potentially be targeted in obesity.
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              Influence of inositol pyrophosphates on cellular energy dynamics.

              With its high-energy phosphate bonds, adenosine triphosphate (ATP) is the main intracellular energy carrier. It also functions in most signaling pathways, as a phosphate donor or a precursor for cyclic adenosine monophosphate. We show here that inositol pyrophosphates participate in the control of intracellular ATP concentration. Yeasts devoid of inositol pyrophosphates have dysfunctional mitochondria but, paradoxically, contain four times as much ATP because of increased glycolysis. We demonstrate that inositol pyrophosphates control the activity of the major glycolytic transcription factor GCR1. Thus, inositol pyrophosphates regulate ATP concentration by altering the glycolytic/mitochondrial metabolic ratio. Metabolic reprogramming through inositol pyrophosphates is an evolutionary conserved mechanism that is also preserved in mammalian systems.
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                Author and article information

                Contributors
                (View ORCID Profile)
                (View ORCID Profile)
                Journal
                BIOMHC
                Biomolecules
                Biomolecules
                MDPI AG
                2218-273X
                June 2023
                May 31 2023
                : 13
                : 6
                : 913
                Article
                10.3390/biom13060913
                10296266
                37371493
                62170102-56a5-44d6-944c-31c9b6258dd1
                © 2023

                https://creativecommons.org/licenses/by/4.0/

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