ArticleiScience2023
Obesity control by SHIP inhibition requires pan-paralog inhibition and an intact eosinophil compartment.
Article in iScience, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
4 citing papers in PubMed, 7 citations in OpenAlex.
- The power of five - inositol polyphosphate 5-phosphatase gene mutations at the intersection of development and disease.FEBS letters · 2026Review
- Approaches to visualize, quantify, and manipulate phosphoinositides in cells.Histochemistry and cell biology · 2026Review
- SHIP inhibition mediates select TREM2-induced microglial functions.Molecular immunology · 2024Article
- Linking adipose tissue eosinophils, IL-4, and leptin in human obesity and insulin resistance.JCI insight · 2024Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
Abstract
Here we extend the understanding of how chemical inhibition of SHIP paralogs controls obesity. We compare different classes of SHIP inhibitors and find that selective inhibitors of SHIP1 or SHIP2 are unable to prevent weight gain and body fat accumulation during increased caloric intake. Surprisingly, only pan-SHIP1/2 inhibitors (pan-SHIPi) prevent diet-induced obesity. We confirm that pan-SHIPi is essential by showing that dual treatment with SHIP1 and SHIP2 selective inhibitors reduced adiposity during excess caloric intake. Consistent with this, genetic inactivation of both SHIP paralogs in eosinophils or myeloid cells also reduces obesity and adiposity. In fact, pan-SHIPi requires an eosinophil compartment to prevent diet-induced adiposity, demonstrating that pan-SHIPi acts via an immune mechanism. We also find that pan-SHIPi increases ILC2 cell function in aged, obese mice to reduce their obesity. Finally, we show that pan-SHIPi also reduces hyperglycemia, but not via eosinophils, indicating a separate mechanism for glucose control.
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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 OpenQuestion graph.