ArticleMolecular metabolism2016
TNP [N2-(m-Trifluorobenzyl), N6-(p-nitrobenzyl)purine] ameliorates diet induced obesity and insulin resistance via inhibition of the IP6K1 pathway.
Article in Molecular metabolism, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 57 citations in OpenAlex.
- Inositol pyrophosphate kinases in health and disease.FEBS letters · 2026Review
- Exercise suppresses IP6K3 to modulate BCAA metabolism and ferroptosis in MASLD.Cellular & molecular biology letters · 2026Article
- Inhibition of IP6K1 suppresses NPA formation via platelet short-chain polyphosphate polymers in necrotizing enterocolitis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Role of Inositol Hexakisphosphate Kinases in Vascular Smooth Muscle Cell Calcification.International journal of molecular sciences · 2026Article
- Integrated Genomic-Metabolomic Analysis for Tri-Categorical Classification of Type 2 Diabetes Status in the Korean Ansan-Ansung Cohort.International journal of molecular sciences · 2025Article
- Physiological roles of phosphoinositides and inositol phosphates: Implications for metabolic dysfunction-associated steatotic liver disease.Clinical science (London, England : 1979) · 2025Review
- Insights into the roles of inositol hexakisphosphate kinase 1 (IP6K1) in mammalian cellular processes.The Journal of biological chemistry · 2024Review
- Functions, Mechanisms, and therapeutic applications of the inositol pyrophosphates 5PP-InsPJournal of cardiovascular translational research · 2024Review
- Synthesis and biological evaluation of flavonoid-based IP6K2 inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2023Article
- The IP6K Inhibitor LI-2242 Ameliorates Diet-Induced Obesity, Hyperglycemia, and Hepatic Steatosis in Mice by Improving Cell Metabolism and Insulin Signaling.Biomolecules · 2023Article
- The Role of Inositols in the Hyperandrogenic Phenotypes of PCOS: A Re-Reading of Larner's Results.International journal of molecular sciences · 2023Review
- Bioinformatics and Next-Generation Data Analysis for Identification of Genes and Molecular Pathways Involved in Subjects with Diabetes and Obesity.Medicina (Kaunas, Lithuania) · 2023Article
- TNP and its analogs: Modulation of IP6K and CYP3A4 inhibition.Journal of enzyme inhibition and medicinal chemistry · 2022Article
- TNP Analogues Inhibit the Virulence Promoting IPBiomolecules · 2022Article
- Pharmacological Inhibition of Inositol Hexakisphosphate Kinase 1 Protects Mice against Obesity-Induced Bone Loss.Biology · 2022Article
- Development of Novel IP6K Inhibitors for the Treatment of Obesity and Obesity-Induced Metabolic Dysfunctions.Journal of medicinal chemistry · 2022Article
- Whole BodyInternational journal of molecular sciences · 2022Article
- Pleiotropic actions of IP6K1 mediate hepatic metabolic dysfunction to promote nonalcoholic fatty liver disease and steatohepatitis.Molecular metabolism · 2021Article
- Histone H4 lysine 16 acetylation controls central carbon metabolism and diet-induced obesity in mice.Nature communications · 2021Article
- The enzymatic activity of inositol hexakisphosphate kinase controls circulating phosphate in mammals.Nature communications · 2021Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveObesity and type 2 diabetes (T2D) lead to various life-threatening diseases such as coronary heart disease, stroke, osteoarthritis, asthma, and neurodegeneration. Therefore, extensive research is ongoing to identify novel pathways that can be targeted in obesity/T2D. Deletion of the inositol pyrophosphate (5-IP7) biosynthetic enzyme, inositol hexakisphosphate kinase-1 (IP6K1), protects mice from high fat diet (HFD) induced obesity (DIO) and insulin resistance. Yet, whether this pathway is a valid pharmacologic target in obesity/T2D is not known. Here, we demonstrate that TNP [N2-(m-Trifluorobenzyl), N6-(p-nitrobenzyl)purine], a pan-IP6K inhibitor, has strong anti-obesity and anti-diabetic effects in DIO mice.
methodsQ-NMR, GTT, ITT, food intake, energy expenditure, QRT-PCR, ELISA, histology, and immunoblot studies were conducted in short (2.5-week)- and long (10-week)-term TNP treated DIO C57/BL6 WT and IP6K1-KO mice, under various diet and temperature conditions.
resultsTNP, when injected at the onset of HFD-feeding, decelerates initiation of DIO and insulin resistance. Moreover, TNP facilitates weight loss and restores metabolic parameters, when given to DIO mice. However, TNP does not reduce weight gain in HFD-fed IP6K1-KO mice. TNP specifically enhances insulin sensitivity in DIO mice via Akt activation. TNP decelerates weight gain primarily by enhancing thermogenic energy expenditure in the adipose tissue. Accordingly, TNP's effect on body weight is partly abolished whereas its impact on glucose homeostasis is preserved at thermoneutral temperature.
conclusionPharmacologic inhibition of the inositol pyrophosphate pathway has strong therapeutic potential in obesity, T2D, and other metabolic diseases.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.