ArticleThe Journal of clinical investigation2016
Adipocyte-specific deletion of Ip6k1 reduces diet-induced obesity by enhancing AMPK-mediated thermogenesis.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 87 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
- Physiological roles of phosphoinositides and inositol phosphates: Implications for metabolic dysfunction-associated steatotic liver disease.Clinical science (London, England : 1979) · 2025Review
- Depleting inositol pyrophosphate 5-InsP7 protected the heart against ischaemia-reperfusion injury by elevating plasma adiponectin.Cardiovascular research · 2024Article
- PAQR4 regulates adipocyte function and systemic metabolic health by mediating ceramide levels.Nature metabolism · 2024Article
- 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
- Kcs1 and Vip1: The Key Enzymes behind Inositol Pyrophosphate Signaling inBiomolecules · 2024Review
- Fragment-Based Screening Identifies New Quinazolinone-Based Inositol Hexakisphosphate Kinase (IP6K) Inhibitors.ACS medicinal chemistry letters · 2023Article
- Article
- The Role of Inositol Hexakisphosphate Kinase in the Central Nervous System.Biomolecules · 2023Review
- β-lapachone regulates mammalian inositol pyrophosphate levels in an NQO1- and oxygen-dependent manner.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Application of Inositol Hexaphosphate and Inositol in Dental Medicine: An Overview.Biomolecules · 2023Review
- The IP6K Inhibitor LI-2242 Ameliorates Diet-Induced Obesity, Hyperglycemia, and Hepatic Steatosis in Mice by Improving Cell Metabolism and Insulin Signaling.Biomolecules · 2023Article
- One Scaffold, Two Conformations: The Ring-Flip of the Messenger InsPBiomolecules · 2023Article
- TNP and its analogs: Modulation of IP6K and CYP3A4 inhibition.Journal of enzyme inhibition and medicinal chemistry · 2022Article
- Pharmacological Inhibition of Inositol Hexakisphosphate Kinase 1 Protects Mice against Obesity-Induced Bone Loss.Biology · 2022Article
- The Inositol Phosphate System-A Coordinator of Metabolic Adaptability.International journal of molecular sciences · 2022Review
- 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
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
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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Registered trials
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.